a bifocated pathway to thiazoles and imidazoles using a … · 2015-12-10 · vineland, nj, usa) or...

Experimental Section

Supporting Information for:

A Bifocated Pathway to Thiazoles and Imidazoles Using a Modular Flow

Microreactor.

Ian R. Baxendale, Steven V. Ley,* Christopher D. Smith, Lucia Tamborini and Ana-Florina

Voica.

Innovative Technology Centre (ACS), Department of Chemistry, University of Cambridge,

Lensfield Road, Cambridge, CB2 1EW, UK.

*Email Address: [email protected]

General procedural information

Acetonitrile (distilled over calcium hydride) was used both as solvent of the flow reactor and as

the solvent to rinse the needles of both liquid-handlers. Flow rates were usually set between 0.05

and 0.1 mL/min per channel depending on the required residence times. In the same manner the

temperature of the chip heating was chosen at between 55 and 85 °C as determined by rapid

optimisation with each starting material. The collection of the products was accomplished using

a second liquid-handler unit supported by a UV-detector. To remove the solvents a Biotage V-

10® solvent evaporator was used.

1H-NMR spectra were recorded in CDCl3 on a Bruker Avance DPX-400 or DPX-500

spectrometer with residual CHCl3 (δH = 7.26 ppm) or MeOH (δH = 3.34 ppm) as the internal

reference). 13C-NMR spectra were recorded in CDCl3 on the same spectrometers with the central

peak of CDCl3 (δC = 77.0 ppm) or MeOH (δC = 49.9 ppm) as the internal reference. DEPT 135

mailto:[email protected]

was used to aid in the assignment of signal in the 13C-NMR spectra. Infra-red spectra were

recorded on a Perkin-Elmer Spectrum One FT-IR spectrometer neat. Letters in the parentheses

refer to relative absorbency of the peak: w, weak, less than 40% of the main peak; m, medium,

ca. 41-74% of the main peak; s, strong, greater than 75% of the most intense peak. Optical

rotations were measured on a Perkin-Elmer Model 343 polarimeter, and [α]D values are reported

in 10-1 deg cm2 g-1; concentration (c) is in g per 100 cm3. LC-MS analysis was performed on an

Agilent HP 1100 series chromatograph (Mercury Luna 3µ C18 (2) column) attached to a Waters

ZQ2000 mass spectrometer with ESCi ionisation source in ESI mode. Elution was carried out

using a reverse phase gradient of acetonitrile/water with both solvents containing 0.1%

trifluoroacetic acid. The gradient is described in Table 1. For HRMS a LCT Premier Micromass

spectrometer was used.

Time/min CH3CN, %Flow rate,

(mL/min)

0.00 5 1

3.00 95 1

5.00 95 1

5.50 5 1

8.00 5 1

Table 1 LC-MS conditions

General description: The reactor configuration and photographic display is given below. All

component parts are commercially available and easily assembled without the aid of specialist

knowledge. The flow reactor is driven by two HPLC-pumps (5 mL pump heads), each

responsible for an independent solvent and integrated reagent stream. These HPLC-pumps are

directly linked to a liquid-handler used for aspirating the starting materials and injecting them

into two separate sample ports to temporary store them in variable 1-10 mL sample loops. The

individual components to construct the reactor were purchased as standard Gilson components or

OEM supplies. Stock solutions of starting materials are retained in teflon sealed vials of several

sizes, standing in racks or in larger flasks if required (upon scale-up). The injecting needle is

rinsed after each step using an attached syringe pump, which is also responsible for the complete

injection process (see above). After injection, the starting materials flow into a glass-mixing chip

where optimal mixing can be achieved. The glass reactor chips were sourced from Syrris Ltd (27

Jarman Way, Royston, Herts SG8 5HW, UK) consisting of 2 reagent inputs and internal volumes

of 62.5 µL, 250 µL and 1000 µL in addition, a chip header was also used to make the connection

of the input and output pipes to the chip. Custom-made heating blocks have been built to allow

reactions at different temperatures. In the next step the reaction mixture is passed through a

series of selection valves which deliver the flow stream into several variable-sized glass columns

containing polymer-supported reagents, scavengers or catalysts. Glass reactor columns used were

Chromaflex or Omnifit and were purchased from Kontes Glass Company (PO Box 1502,

Vineland, NJ, USA) or Omnifit (Bio-Chem Valve/Omnifit. 2 College Park, Coldhams Lane,

Cambridge, CB1 3HD, UK) respectively. A heating or cooling system for these columns is also

available to control the reaction temperature, including the Vapourtec R4 column heater

(obtained from Vapourtec Ltd, Place Farm, Ingham, Suffolk, IP31 1NQ, UK) for the heating

requirements. The flowing material then passes through a UV-unit allowing the monitoring of

the reactions progress. Finally, the system is connected to a second liquid-hander collecting the

products of subsequent reactions into different sized glass vials. Furthermore, HPLC-columns

can be applied in-line to purify intermediates or products if necessary in a fully automated

fashion. The entire process is computer controlled for repeatability and ease of use.

Figure 1. Flow reactor setup.

Synthesis of starting materials:

O

NH

NO2

Br

2-Bromo-N-(2-nitrophenyl)acetamide (12): To a solution of 2-nitroaniline (0.68 g, 5 mmol)

and bromoacetylbromine (870 µL, 10 mmol) in CH2Cl2 (30 mL) was added polymer-supported

triethylamine (7.8 g, 25 mmol; 3.2 mmol/g). The reaction mixture was shaken at ambient

temperature for 4 h. Polymer-supported trisamine (1.2 g, 5 mmol, 4.36 mmol/g) was added and

the mixture shaken for 1 h to scavenger the excess bromoacetylbromine. After filtration and

evaporation of the solvent, the desired product was obtain as yellow solid in pure form requiring

no further purification. Yield 1230 mg; 95%. Rt 4.11, M+H m/z = FRG 214.1 & 216.1 (1:1); 1H-

NMR (400 MHz, CDCl3): δ/ppm = 11.08 (1 H, br. s), 8.67 (1 H, dd, J = 1.10, 8.42 Hz), 8.21 (1

H, dd, J = 1.46, 8.42 Hz), 7.66 (1 H, ddd, J = 1.46, 7.32, 8.42 Hz), 7.22 (1 H, ddd, J = 1.10, 7.32,

8.42 Hz), 4.07 (2 H, s); 13C-NMR (100 MHz, CDCl3): δ/ppm = 171.55(C), 165.56(C),

136.30(CH), 134.13(C), 126.26(CH), 124.73(CH), 122.44(CH), 43.54(CH2). IR (neat) ν

3310(w), 1692(m), 1607(m), 1588(s), 1547(w), 1500(s), 1457(m), 1437(m), 1341(s), 1313(w),

1280(s), 1229(w), 1164(w), 1148(m), 784(w), 744(m), 715(w) cm-1. HRMS calculated for

C8H8BrN2O3 258.9718; found 258.9722.

S

N

NH

OHO

HOOH

OH O

OEt

Ethyl 5-((2R,3S,4S,5S)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl-

amino)thiazole-4-carboxylate: To a solution of (2R,3R,4S,5S,6R)-2-(acetoxymethyl)-6-(4-

(ethoxycarbonyl)thiazol-5-ylamino)tetrahydro-2H-pyran-3,4,5-triyl triacetate (14) (1.3 g, 2.5

mmol) in of MeOH (5 mL) was added polymer-supported carbonate (2.8 g, 10 mmol, 3.5

mmol/g) and the reaction stirred for 8 h at ambient temperature. The resin was filtered and

washed with methanol. After the removal of the solvent from the solution the product was

obtained in quantitative yield and excellent purity requiring no further purification. Yield 835

mg; 100%. 1H-NMR (400 MHz, d4-MeOH): δ/ppm = 8.15 (1 H, s), 4.40 (1 H, d, J = 8.42 Hz),

4.35 (2 H, q, J = 7.32 Hz), 3.87 (1 H, m), 3.71 (1 H, dd, J = 4.76, 12.07 Hz), 3.41 (4 H, m), 1.37

(3 H, t, J = 7.32 Hz); 13C-NMR (100 MHz, d4-MeOH): δ/ppm = 164.00(C), 159.22(C),

138.37(CH), 121.85(C), 88.38(CH), 78.00(CH), 77.29(CH), 73.14(CH), 69.95(CH), 61.07(CH2),

60.25(CH2), 13.37(CH3). IR (neat) ν 3250(w), 1665(m), 1537(s), 1417(m), 1383(m), 1232(s),

1185(m), 1083(s), 1024(s), 846(m), 769(s) cm-1. HRMS calculated for C12H19N2O7S 335.0913;

found 335.0902.

S

N

N

ONa

MeO

O

O

Br

Sodium 4-(4-bromophenyl)-6-(methoxycarbonyl)-5-oxo-4,5-dihydrothiazolo[5,4-b]pyridin-

7-olate (11): To a solution of 5-(4-bromophenylamino)-thiazole-4-carboxylic acid ethyl ester (2)

(328 mg, 1 mmol) in THF (10 mL) was added methylmalonylchloride (107 µL, 1 mmol) and the

reaction mixture heated in a 20 mL microwave vial under microwave irradiation for 30 min at

100 ºC. After removal of the solvent, the crude amide was dissolved in 5 mL of methanol and

added to a solution of NaOMe {prepared from metallic Na (23 mg, 1 mmol) in MeOH (5 mL)}.

The reaction mixture was stirred for 30 min at ambient temperature. The desired compound

precipitates a sodium salt, which was filtered and dried. Yield 268 mg; 70% (after two steps). Rt

4.06, M+Na m/z = 403.0 & 405.0 (1:1); 1H-NMR (400 MHz, d6-DMSO): δ/ppm = 8.68 (1 H, s),

7.75 (2 H, d, J = 8.42 Hz), 7.41 (2 H, d, J = 8.42 Hz), 3.67 (3 H, s); 13C-NMR (100 MHz, d6-

DMSO): δ/ppm = 170.82(C), 169.57(C), 161.49(C), 145.147(C), 141.84(CH), 141.06(C),

137.36(C), 132.45(CH), 130.44(CH), 121.19(C), 100.02(C), 50.33(CH3). IR (neat) ν 3056 (w),

1685(s), 1659(m), 1567(s), 1523(s), 1486(m), 1467(s), 1448(s), 1398(w), 1346(s), 1317(m),

1296(w), 1260(w), 1232(m), 1212(s), 1194(m), 1060(m), 1010(s), 931(w), 873(w), 814(m),

793(s), 741(m), 706(w) cm-1. HRMS calculated for C14H9BrN2O4SNa 402.9364; found

402.9384.

General reaction procedure PART 1: Two 0.75 M solutions of the ethyl isocyanoacetate and

the corresponding isothiocyanate were prepared in MeCN or in a mixture MeCN/THF 9/1

depending on the starting material solubility. Using an automated injection system, 4.5 mL of

each solution (3.38 mmol) were transferred at a constant flow rate (0.05-0.1 mL/min) onto a

preheated chip maintained at 55-85 ºC. The reactor chip was connected to a column (i.d. 6.6 mm)

packed with PS-BEMP (2.5 g, ~5.5 mmol) also maintained at 55-85 ºC. The reaction takes place

on the columns and the product was collected automatically as a solution triggered by UV

threshold detection. While the reaction is proceeding the PS-BEMP is observed to change colour

and darken to a deep red. After the removal of the solvent from the eluted solution the thiazole

adduct was obtained in a pure form requiring no further purification.

General reaction procedure to obtain the imidazole product from aromatic isothiocyanate

PART 2: A 0.75 M solution of an electrophile was prepared in acetonitrile and 2.5 mL (1.86

mmol)were injected in flow. The solution passed through the column containing PS-BEMP and

the corresponding imidazole was collected. After removal of the solvent the product was

obtained in a pure form requiring no further purification.

S

N

HN

Cl

EtO

O

5-(4-Chlorophenylamino)thiazole-4-carboxylic acid ethyl ester: Yield 450 mg; 47%. Rt 4.63,

M-H m/z = 283.5; 1H-NMR (400 MHz, CDCl3): δ/ppm = 9.78 (1 H, br. s), 7.97 (1 H, s), 7.31 (2

H, d, J = 9.06 Hz), 7.16 (2 H, d, J = 9.06 Hz), 4.42 (2 H, q, J = 7.14 Hz), 1.43 (3 H, t, J = 7.14

Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm = 165.20(C), 154.51(C), 139.27(C), 135.22(CH),

129.70(CH), 128.81(C), 123.82(C), 119.44(CH), 61.06(CH2), 14.46(CH3). IR (neat) ν 1660(m),

1588(m), 1538(s), 1493(m), 1462(m), 1428(s), 1405(m), 1382(m), 1353(w), 1294(m), 1249(s),

1205(s), 1185(s), 1121(w), 1093(m), 1028(m), 963(w), 861(m), 838(m), 817(m), 764(m),

733(w), 709(w) cm-1. HRMS calculated for C12H11ClN2O2SNa 305.0127; found 305.0139.

N

N

S

Cl

EtO

O

O

O

1-(4-Chlorophenyl)-5-[2-(4-methoxyphenyl)-2-oxo-ethylsulfanyl]-1H-imidazole-4-

carboxylic acid ethyl ester: Yield 700 mg; 48%. Rt 4.56, M+H m/z = 431.5; 1H-NMR (400

MHz, CDCl3): δ/ppm = 7.66 (1 H, s), 7.66 (2 H, d, J = 8.78 Hz), 7.29 (2 H, d, J = 8.78 Hz), 7.12

(2 H, d, J = 8.78 Hz ), 6.79 (2 H, d, J = 8.78 Hz), 4.35 (2 H, q, J = 7.14 Hz), 4.17 (2 H, s), 3.80

(3 H, s), 1.35 (3 H, t, J = 7.14 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm = 191.81(C),

163.86(C), 162.19(C), 138.96(CH), 136.93(C), 135.27(C), 133.17(C), 130.80(CH), 129.26(CH),

129.05(C), 128.18(CH), 127.92(C), 113.85(CH), 60.99(CH2), 55.48(CH3), 41.15(CH2),

14.29(CH3). IR (neat) ν 2978(w), 1709(m), 1666(m), 1598(s), 1574(m), 1509(m), 1495(s),

1421(w), 1380(w), 1313(m), 1282(m), 1258(s), 1173(s), 1112(w), 1092(m), 1050(m), 1016(m),

958(m), 835(m), 787(w), 735(w), 666(w) cm-1. HRMS calculated for C21H19ClN2O4SNa

453.0652; found 453.0650.

S

N

HN

Br

EtO

O

5-(4-Bromophenylamino)thiazole-4-carboxylic acid ethyl ester: Yield 642 mg; 58%. Rt 4.64,

M+H m/z = 327.3 & 329.3 (1:1); 1H-NMR (400 MHz, CDCl3): δ/ppm = 9.79 (1 H, br. s), 7.97 (1

H, s), 7.45 (2 H, d, J = 9.15 Hz), 7.10 (2 H, d, J = 9.15 Hz), 4.42 (2 H, q, J = 7.32 Hz), 1.42 (3 H,

t, J = 7.32 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm = 164.23(C), 154.80(C), 141.27(C),

138.15(CH), 132.75(CH), 124.73(CH), 121.15(C), 115.56(C), 60.57(CH2), 14.77(CH3). IR (neat)

ν 1715(w), 1662(m), 1586(m), 1544(s), 1491(m), 1428(m), 1403(w), 1382(w), 1296(w), 1252(s),

1206(m), 1186(s), 1074(w), 1029(w), 860(w), 815(w), 764(w) cm-1. HRMS calculated for

C12H11BrN2O2SNa 348.9622; found 348.9616.

N

N

S

Br

EtO

O

O

Br

1-(4-Bromophenyl)-5-[2-(4-bromophenyl)-2-oxo-ethylsulfanyl]-1H-imidazole-4-carboxylic

acid ethyl ester (4): Yield 672 mg; 38%. Rt 4.72, M+H m/z = 525.1; 1H-NMR (400 MHz,

CDCl3): δ/ppm = 7.69 (1 H, s), 7.61 (2 H, d, J = 8.78 Hz), 7.54 (2 H, d, J = 8.65 Hz), 7.52 (2 H,

d, J = 8.65 Hz), 7.12 (2 H, d, J = 8.78 Hz), 4.41 (2 H, q, J = 7.32 Hz), 4.24 (2 H, s), 1.42 (3 H, t,

J = 7.32 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm = 192.63(C), 162.67(C), 139.35(CH),

137.80(C), 137.68(C), 134.04(C), 132.78(CH), 132.34(CH), 130.35(CH), 129.42(C), 128.91(C),

128.83(CH), 124.02(C), 61.54(CH2), 41.67(CH2), 14.75(CH3). IR (neat) ν 3124(w), 2980(w),

1703(m), 1673(s), 1585(m), 1566(w), 1490(s), 1413(w), 1394(w), 1378(m), 1325(m), 1309(w),

1281(m), 1263(m), 1177(s), 1148(m), 1128(w), 1108(w), 1068(m), 1040(m), 1004(s), 958(m),

866(m), 837(s), 820(m), 764(m), 749(m), 731(m), 710(m), 664(m) cm-1. HRMS calculated for

C20H16Br2N2O3SNa 544.9146; found 544.9149.

N

N

HS

Br

EtO

O

Ethyl 1-(4-bromophenyl)-5-(methylthio)-1H-imidazole-4-carboxylate: Yield 368 mg; 32%.

Rt 4.43, M+H m/z = 341.2 & 343.2 (1:1); 1H-NMR (400 MHz, CDCl3): δ/ppm = 7.63 (1 H, s),

7.57 (2 H, d, J = 8.78 Hz), 7.16 (2 H, d, J = 8.78 Hz), 4.33 (2 H, q, J = 7.32 Hz), 2.20 (3 H, s),

1.33 (3 H, t, J = 7.32 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm = 162.12(C), 138.32(CH),

136.18(C), 134.05(C), 132.60(CH), 131.94(C), 127.99(CH), 123.39(C), 60.86(CH2), 19.24(CH3),

14.36(CH3). IR (neat) ν 1709(s), 1490(s), 1315(m), 1246(s), 1181(s), 1100(w), 1069(w), 1047(s),

1009(m), 955(s), 829(m), 787(w), 664(w); cm-1. HRMS calculated for C13H14BrN2O2S 340.9959;

found 340.9969.

N

N

S

Br

EtO

O

O

NH2

Ethyl 5-(2-amino-2-oxoethylthio)-1-(4-bromophenyl)-1H-imidazole-4-carboxylate (18):

Yield 388 mg; 30%. Rt 4.00, M+H m/z = 384.1 & 386.1 (1:1); 1H-NMR (400 MHz, CDCl3):

δ/ppm = 7.73 (1 H, s), 7.66 (2 H, d, J = 8.78 Hz), 7.49 (1 H, br. s), 7.27 (2 H, d, J = 8.78 Hz),

5.86 (1 H, br. s), 4.41 (2 H, q, J = 7.32 Hz), 3.21 (2 H, s), 1.42 (3 H, t, J = 7.32 Hz); 13C-NMR

(100 MHz, CDCl3): δ/ppm = 169.92(C), 162.90(C), 139.57(CH), 136.85(C), 133.47(C),

132.87(CH), 128.29(CH), 124.03(C), 119.69(C), 61.46(CH2), 38.47(CH2), 14.30(CH3). IR (neat)

ν 3411(w), 3289(w), 1706(s), 1663(s), 1590(w), 1561(w), 1491(s), 1438(w), 1401(m), 1376(m),

1333(w), 1304(w), 1263(m), 1239(m), 1177(s), 1136(m), 1101(m), 1048(s), 1012(m), 960(s),

911(w), 876(m), 837(m), 821(m), 732(m), 662(m) cm-1. HRMS calculated for C14H14BrN3O3SNa

405.9837; found 405.9852.

N

N

S

Br

EtO

O

O

NH

NO2

Ethyl 1-(4-bromophenyl)-5-(2-(2-nitrophenylamino)-2-oxoethylthio)-1H-imidazole-4-

carboxylate (13): Yield 511 mg; 30%. Rt 4.48, M+H m/z = 505.2 & 507.2 (1:1); 1H-NMR (400

MHz, CDCl3): δ/ppm = 10.54 (1 H, br. s), 8.48 (1 H, dd, J = 0.85, 8.44 Hz), 8.18 (1 H, dd, J =

1.35, 8.35 Hz), 7.68 (1 H, s), 7.60 (1 H, ddd, J = 1.35, 7.25, 8.44 Hz), 7.45 (2 H, d, J = 8.78 Hz),

7.21 (1 H, ddd, J = 0.85, 7.25, 8.35 Hz), 7.15 (2 H, d, J = 8.78 Hz), 4.39 (2 H, q, J = 7.32 Hz),

3.70 (2 H, s), 1.39 (3 H, t, J = 7.32 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm = 166.60(C),

162.19(C), 139.33(CH), 137.56(C), 136.68(C), 135.65(CH), 133.95(C), 133.62(C), 132.53(CH),

128.31(CH), 127.75(C), 125.87(CH), 123.72(CH), 123.68(C), 121.93(CH), 61.25(CH2),

41.09(CH2), 14.29(CH3). IR (neat) ν 1707(m), 1696(m), 1606(w), 1582(w), 1492(m), 1448(w),

1433(w), 1333(m), 1317(m), 1263(s), 1197(m), 1146(w), 1106(m), 1072(w), 1046(m), 1008(w),

957(m), 919(w), 855(w), 839(m), 789(m), 710(s), 704(s), 666(m) cm-1. HRMS calculated for

C20H18BrN4O5S 505.0181; found 505.0194.

S

N

HN

O

EtO

O

5-(4-Methoxyphenylamino)thiazole-4-carboxylic acid ethyl ester: Yield 900 mg; 96%. Rt

4.31, M+H m/z = 279.4; 1H-NMR (400 MHz, CDCl3): δ/ppm = 9.43 (1 H, br. s), 7.87 (1 H, s),

7.21 (2 H, d, J = 8.78 Hz), 6.92 (2 H, J = 8.78 Hz), 4.44 (2 H, q, J = 7.32 Hz), 3.79 (3 H, s), 1.45

(3 H, t, J = 7.32 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm = 165.21(C), 157.52(C), 156.80(C),

134.21(CH), 126.91(C), 122.36(C), 121.47(CH), 114.90(CH), 60.74(CH2), 55.53(CH3),

14.45(CH3). IR (neat) ν 1657(m), 1593(w), 1536(s), 1510(s), 1461(m), 1430(m), 1412(m),

1382(m), 1353(w), 1240(s), 1205(m), 1180(s), 1112(w), 1029(s), 962(w), 864 (w), 824(m),

760(m) cm-1. HRMS calculated for C13H14N2O3SNa 301.0623; found 301.0636.

N

N

S

O

EtO

O

O

Ph

1-(4-Methoxyphenyl)-5-(2-oxo-2-phenyl-ethylsulfanyl)-1H-imidazole-4-carboxylic acid

ethyl ester: Yield 53 mg; 4%. Rt 4.40, M+H m/z = 397.5; 1H-NMR (400 MHz, CDCl3): δ/ppm =

7.73 (2 H, m), 7.63 (1 H, s), 7.50 (1 H, m), 7.35 (2 H, m), 7.09 (2 H, d, J = 8.78 Hz), 6.84 (2 H,

d, J = 8.78 Hz), 4.36 (2 H, q, J = 7.13 Hz), 4.25 (2 H, s), 3.78 (3 H, s), 1.37 (3 H, t, J = 7.13 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm = 193.39(C), 162.44(C), 160.06(C), 139.29(CH),

136.58(C), 135.18(C), 133.39(CH), 129.41(C), 128.53(CH), 128.48(CH), 128.05(CH),

127.52(C), 114.26(CH), 60.89(CH2), 55.49(CH3), 41.44(CH2), 14.34(CH3). IR (neat) ν 2980(w),

1703(m), 1675(m), 1609(w), 1597(w), 1580(w), 1512(s), 1480(m), 1448(m), 1381(w), 1313(m),

1275(m), 1243(s), 1181(s), 1109(w), 1051(s), 1031(m), 1014(m), 1001(m), 960(m), 910(m),

834(m), 800(w), 787(w), 728(s), 688(m), 669(m) cm-1. HRMS calculated for C21H21N2O4S

397.1222; found 397.1212.

S

N

HN

EtO

O

O


4.42, M-H m/z = 277.6; 1H-NMR (400 MHz, CDCl3): δ/ppm = 9.79 (1 H, br. s), 7.95 (1 H, s),

7.25 (1 H, t, J = 8.14 Hz), 6.82 (1 H, ddd, J = 0.78, 2.36, 8.14 Hz), 6.76 (1 H, t, J = 2.36 Hz),

6.63 (1 H, ddd, J = 0.78, 2.36, 8.14 Hz), 4.42 (2 H, q, J = 7.13 Hz), 3.79 (3 H, s), 1.43 (3 H, t, J =

7.13 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm = 165.23(C), 160.77(C), 154.66(C), 141.83(C),

135.22(CH), 130.47(CH), 123.52(C), 110.41(CH), 109.29(CH), 104.06(CH), 60.95(CH2),

55.62(CH3), 14.48(CH3). IR (neat) ν 1661(m), 1597(s), 1547(s), 1494(m), 1455(m), 1437(m),

1416(s), 1383(m), 1354(w), 1339(w), 1264(s), 1230(s), 1186(s), 1156(s), 1093(w), 1031(m),

840(m), 765(m), 686(w) cm-1. HRMS calculated for C13H14N2O3SNa 301.0623; found 301.0618.

N

N

S

EtO

O

O

Br

O

Ethyl 5-(2-(4-bromophenyl)-2-oxoethylthio)-1-(3-methoxyphenyl)-1H-imidazole-4-

carboxylate: Yield 420 mg; 26%. Rt 4.60, M+H m/z = 475.5 & 477.5 (1:1); 1H-NMR (400 MHz,

CDCl3): δ/ppm = 7.62 (1 H, s), 7.53 (2 H, d, J = 8.42 Hz), 7.41 (2 H, d, J = 8.42 Hz), 7.20 (1 H,

t, J = 8.42 Hz), 6.85 (1 H, m), 6.70 (2 H, m), 4.30 (2 H, q, J = 6.95 Hz), 4.15 (2 H, s), 3.71 (3 H,

s), 1.31 (3 H, t, J = 6.95 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm = 193.34(C), 162.27(C),

159.89(C), 139.15(CH), 136.89(C), 135.59(C), 133.71(C), 131.75(CH), 129.96(CH),

129.87(CH), 128.55(C), 128.48(C), 118.85(CH), 114.66(CH), 112.86(CH), 60.91(CH2),

55.49(CH3), 41.21(CH2), 14.31(CH3). IR (neat) ν 1704(m), 1677(m), 1605(m), 1585(s),

1568(w), 1491(s), 1396(w), 1378(w), 1313(m), 1270(s), 1219(s), 1185(s), 1138(m), 1070(m),

1055(s), 1035(m), 1005(s), 972(m), 847(m), 786(m), 749(w), 734(w), 693(m), 663(w) cm-1.

HRMS calculated for C21H20BrN2O4SNa 475.0300; found 475.0321.

S

N

HN

EtO

O

NO2

5-(4-Nitrophenylamino)thiazole-4-carboxylic acid ethyl ester: Yield 960 mg; 97%. Rt 4.37,

M+H m/z = 294.8; 1H-NMR (400 MHz, CDCl3): δ/ppm = 10.41 (1 H, br. s), 8.25 (2 H, d, J = 9.15

Hz), 8.17 (1 H, s), 7.27 (2 H, d, J = 9.15 Hz), 4.45 (2 H, q, J = 7.13 Hz), 1.44 (3 H, t, J = 7.13

Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm = 165.12(C), 150.93(C), 145.55(C), 142.37(C),

137.29(CH), 126.25(C), 125.97(CH), 116.05(CH), 61.58(CH2), 14.37(CH3). IR (neat) ν

3088(w), 1659(m), 1597(m), 1561(s), 1504(s), 1438(m), 1414(m), 1385(w), 1331(s), 1312(m),

1257(s), 1216(s), 1190(s), 1127(m), 1112(s), 1028(m), 966(w), 847 (m), 828(m), 775(m),

748(m), 735(w), 685(w) cm-1. HRMS calculated for C12H12N3O4S 294.0549; found 294.0539.

S

N

HN

EtO

O

Cl

Cl

5-(3,4-Dichlorophenylamino)thiazole-4-carboxylic acid ethyl ester: Yield 535 mg; 50%. Rt


7.40 (1 H, d, J = 8.74 Hz), 7.34 (1 H, d, J = 2.74 Hz), 7.06 (1 H, dd, J = 2.74, 8.74 Hz), 4.43 (2

H, q, J = 7.13 Hz), 1.43 (3 H, t, J = 7.13 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm = 165.15(C),

153.46(C), 140.08(C), 135.83(CH), 133.57(C), 131.19(CH), 126.79(C), 124.49(C), 119.47(CH),

117.29(CH), 61.24(CH2), 14.43(CH3). IR (neat) ν 3047(w), 2988(w), 1655(s), 1578(s), 1541(s),

1477(m), 1460(w), 1428(s), 1405(m), 1377(s), 1352(w), 1313(m), 1259(s), 1242(s), 1205(s),

1193(s), 1148(m), 1133(m), 1023(s), 970(m), 917(w), 865(w), 842(m), 815(m), 795(m), 772(s),

750(m) cm-1. HRMS calculated for C12H10Cl2N2O2SNa 338.9738; found 338.9744.

N

N

S

EtO

O

O

CN

Cl

Cl

5-[2-(4-Cyanophenyl)-2-oxo-ethylsulfanyl]-1-(3,4-dichlorophenyl)-1H-imidazole-4-

carboxylic acid ethyl ester: Yield 410 mg; 26%. Rt 4.61, M+H m/z = 460.4; 1H-NMR (400

MHz, CDCl3): δ/ppm = 7.81 (2 H, d, J = 8.78 Hz), 7.70 (1 H, s), 7.67 (2 H, d, J = 8.78 Hz), 7.41

(1 H, d, J = 8.41 Hz), 7.33 (1 H, d, J = 2.56 Hz), 7.11 (1 H, dd, J = 2.56, 8.41 Hz), 4.36 (2 H, q, J

= 7.32 Hz), 4.24 (2 H, s), 1.37 (3 H, t, J = 7.32 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm =

191.74(C), 162.09(C), 139.03(CH), 137.53(C), 134.00(C), 133.67(C), 133.23(C), 132.37(CH),

130.74(CH), 128.85(CH), 128.78(CH), 127.93(C), 126.36(CH), 117.58(C), 116.77(C),

116.35(C), 61.22(CH2), 41.30(CH2), 14.30(CH3). IR (neat) ν 2989(w), 2253(w), 2229(w),

1711(m), 1671(m), 1605(w), 1568(w), 1508(w), 1482(s), 1446(w), 1421(w), 1405(m), 1374(w),

1314(m), 1294(w), 1272(s), 1245(s), 1193(s), 1151(w), 1133(m), 1054(m), 1026(m), 1012(m),

970(m), 918(w), 878(w), 862(m), 818(m), 772(m), 738(s), 699(m), 686(w), 664(m) cm-1. HRMS

calculated for C21H16Cl2N3O3S 460.0270; found 460.0283.

S

N

HN

EtO

O

CF3F3C

5-(3,5-Bis-trifluoromethylphenylamino)thiazole-4-carboxylic acid ethyl ester: Yield 540 mg;

42%. Rt 5.01, M+H m/z = 385.4; 1H-NMR (400 MHz, CDCl3): δ/ppm = 10.23 (1 H, br. s), 8.12

(1 H, s), 7.63 (2 H, m), 7.54 (1 H, m), 4.45 (2 H, q, J = 7.13 Hz), 1.44 (3 H, t, J = 7.13 Hz); 13C-

NMR (100 MHz, CDCl3): δ/ppm = 165.17(C), 152.04(C), 141.86(C), 136.58(CH), 133.24(C, q,

J = 33.64 Hz), 125.67(C), 122.89(C, q, J = 273.00 Hz), 116.91(CH, m), 116.33(CH, m),

61.52(CH2), 14.34(CH3). IR (neat) ν 2983(w), 1714(w), 1668(m), 1622(w), 1560(s), 1473(m),

1425(w), 1377(s), 1328(w), 1277(s), 1255(s), 1207(s), 1181(s), 1136(s), 1099(m), 1063(w),

1029(m), 999(w), 973(w), 946(w), 881(w), 848(w), 768(w), 701(w), 684(m) cm-1. HRMS

calculated for C14H10F6N2O2SNa 407.0265; found 407.0250.

N

N

S

EtO

O

O

O

CF3

F3C

1-(3,5-Bis-trifluoromethylphenyl)-5-[2-(4-methoxyphenyl)-2-oxo-ethylsulfanyl]-1H-

imidazole-4-carboxylic acid ethyl ester: Yield 935 mg; 52%. Rt 4.80, M+H m/z = 533.5; 1H-

NMR (400 MHz, CDCl3): δ/ppm = 7.86 (1 H, s), 7.79 (1 H, m), 7.77 (2 H, m), 7.66 (2 H, d, J =

8.78 Hz), 6.84 (2 H, d, J = 8.78 Hz), 4.44 (2 H, q, J = 7.32 Hz), 4.24 (2 H, s), 3.84 (3 H, s), 1.43

(3 H, t, J = 7.32 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm = 191.48(C), 163.91(C), 161.99(C),

138.68(CH), 137.53(C), 136.06(C), 132.67(C, q, J = 34.2 Hz), 130.69(CH), 129.27(C),

127.58(C), 127.46(CH), 122.93(CH, m), 122.43(C, q, J = 271.4 Hz), 113.80(CH, m),

61.32(CH2), 55.45(CH3), 40.89(CH2), 14.31(CH3). IR (neat) ν 1713(w), 1667(w), 1598(m),

1574(w), 1511(w), 1484(w), 1407(w), 1338(w), 1314(w), 1276(s), 1258(s), 1171(s), 1133(s),

1110(m), 1062(s), 1019(w), 897(w), 841(m), 806(w), 788(w), 774(w), 735(w), 712(w), 701(m),

684(m), 668(w) cm-1. HRMS calculated for C23H18F6N2O4SNa 555.0789; found 555.0788.

S

N

HN

EtO

O

F

5-(3-Fluorophenylamino)thiazole-4-carboxylic acid ethyl ester: Yield 610 mg; 68%. Rt 4.42,

M+H m/z = 267.4; 1H-NMR (400 MHz, CDCl3): δ/ppm = 9.88 (1 H, br. s), 7.99 (1 H, s), 7.28 (1

H, m), 6.96 (1 H, m), 6.93 (1 H, t, J = 2.30 Hz), 6.75 (1 H, ddd, J = 0.82, 2.30, 8.29 Hz), 4.41 (2


163.46(C, d, J = 246.01 Hz), 153.68(C), 142.08(C, d, J = 10.38 Hz), 135.66(CH), 130.94(CH, d,

J = 10.38 Hz), 124.11(C), 113.49(CH, d, J = 3.11 Hz), 110.25 (CH, d, J = 21.80 Hz), 104.89

(CH, d, J = 25.95 Hz), 61.10(CH2), 14.43(CH3). IR (neat) ν 1662(m), 1614(m), 1593(m),

1544(s), 1493(m), 1453(m), 1415(s), 1383(m), 1354(w), 1261(s), 1218(s), 1186(s), 1145(s),

1094(w), 1027(s), 1003(w), 981(w), 959(w), 840(s), 764(s), 704(w), 679(m) cm-1. HRMS

calculated for C12H11FN2O2SNa 289.0423; found 289.0423.

N

N

S

EtO

O

O

Br

F

5-[2-(4-Bromophenyl)-2-oxo-ethylsulfanyl]-1-(3-fluorophenyl)-1H-imidazole-4-carboxylic

acid ethyl ester: Yield 440 mg; 28%. Rt 4.64, M+H m/z = 463.7; 1H-NMR (400 MHz, CDCl3):

δ/ppm = 7.70 (1 H, s), 7.62 (2 H, d, J = 8.78 Hz), 7.52 (2 H, d, J = 8.78 Hz), 7.37 (1 H, t, J =

8.31 Hz), 7.13 (1 H, dt, J= 2.11, 8.31 Hz), 7.03 (1 H, m), 6.99 (1 H, t, J = 2.11 Hz), 4.40 (2 H, q,

J = 7.32 Hz), 4.26 (2 H, s), 1.41 (3 H, t, J = 7.32 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm =

192.25(C), 162.48(C, d, J = 249.65 Hz), 162.25(C), 138.99(CH), 137.20(C), 135.90(C, d, J =

9.99 Hz), 133.69(C), 132.07(C), 131.91(CH), 130.46(CH, d, J = 8.79 Hz), 129.95(CH),

128.83(C), 122.71(CH, d, J = 3.20 Hz), 116.46(CH, d, J = 21.17 Hz), 114.68(CH, d, J = 24.37

Hz), 61.12(CH2), 41.23(CH2), 14.33(CH3). IR (neat) ν 1703(m), 1675(m), 1609(w), 1598(m),

1584(s), 1568(w), 1489(s), 1454(m), 1396(m), 1380(w), 1312(m), 1265(s), 1199(s), 1131(w),

1070(m), 1050(m), 1021(w), 1005(s), 861(s), 839(m), 786(m), 763(m), 749(w), 689(m), 660(w)

cm-1. HRMS calculated for C20H16FBrN2O3SNa 484.9947; found 484.9960.

S

N

HN

EtO

O

O



7.37 (1 H, dd, J = 2.20, 7.32 Hz), 6.99 (2 H, m), 6.91 (1 H, dd, J = 1.83, 7.32 Hz), 4.46 (2 H, q, J

= 6.95 Hz), 3.97 (3 H, s), 1.48 (3 H, t, J = 6.95 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm =

164.89(C), 153.52(C), 148.86(C), 135.10(CH), 130.20(C), 124.00(C), 123.10(CH), 120.80(CH),

114.52(CH), 110.74(CH), 60.80(CH2), 55.96(CH3), 14.43(CH3). IR (neat) ν 2979(w), 1713(w),

1663(m), 1599(m), 1542(s), 1494(m), 1463(m), 1416(s), 1382(m), 1353(w), 1251(s), 1233(s),

1200(m), 1182(s), 1115(s), 1094(w), 1050(w), 1025(s), 960(w), 862(w), 837(w), 734(s) cm-1.

HRMS calculated for C13H15N2O3S 279.0803; found 279.0796.

N

N

S

EtO

O

O O

1-(2-Methoxyphenyl)-5-(2-oxo-2-phenyl-ethylsulfanyl)-1H-imidazole-4-carboxylic acid

ethyl ester: Yield 100 mg; 7.5%. Rt 4.41, M+H m/z = 397.6; 1H-NMR (400 MHz, CDCl3):

δ/ppm = 7.74 (2 H, d, J = 8.42 Hz), 7.56 (1 H, s), 7.50 (1 H, m), 7.35 (3 H, m), 7.02 (1 H, dd, J =

1.83, 7.68 Hz), 6.92 (2 H, m), 4.39 (2 H, q, J = 7.32 Hz), 4.31 (2 H, s), 3.71 (3 H, s), 1.39 (3 H, t,

J = 7.32 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm = 193.69(C), 162.56(C), 154.53(C),

139.25(CH), 135.88(C), 135.33(C), 133.36(CH), 131.02(CH), 128.59(CH), 128.52(CH),

128.44(CH), 125.43(C), 123.69(C), 120.50(CH), 111.69(CH), 60.83(CH2), 55.60(CH3),

41.80(CH2), 14.38(CH3). IR (neat) ν 2981(w), 1708(s), 1678(s), 1598(m), 1580(w), 1507(s),

1480(m), 1449(m), 1380(w), 1363(w), 1314(m), 1273(s), 1261(s), 1235(s), 1184(s), 1117(w),

1053(m), 1023(m), 960(m), 911(m), 754(m), 733(s), 689(w) cm-1. HRMS calculated for

C21H20N2O4SNa 419.1041; found 419.1029.

S

N

HN

EtO

O

O

Ethyl 5-benzamidothiazole-4-carboxylate: Yield 802 mg; 86%. Rt 4.16, M+H m/z = FRG

190.8; 1H-NMR (400 MHz, CDCl3): δ/ppm = 11.80 (1 H, br. s), 8.38 (1 H, s), 8.01 (2 H, ap. d, J

= 8.42 Hz), 7.61 (1 H, ap. t, J = 7.68 Hz), 7.53 (2 H, ap. dd, J = 7.68, 8.42 Hz), 4.50 (2 H, q, J =

7.32 Hz), 1.47 (3 H, t, J = 7.32 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm = 165.27(C),

163.67(C), 145.30(C), 144.71(CH), 133.17(CH), 131.39(C), 129.10(CH), 128.43(C),

127.59(CH), 61.78(CH2), 14.36(CH3). IR (neat) ν 3284(w), 1677(m), 1658(s), 1599(w), 1532(s),

1472(m), 1458(m), 1443(m), 1398(w), 1377(m), 1262(s), 1227(s), 1191(s), 1110(w), 1070(w),

1031(m), 1001(w), 979(w), 872(m), 845(w), 818(w), 799(w), 778(m), 706(m), 687(m), 677(m)

cm-1. HRMS calculated for C13H12N2O3SNa 299.0466; found 299.0475.

S

N

HN

EtO

O

Cl

(S)-Ethyl 5-(1-(4-chlorophenyl)ethylamino)thiazole-4-carboxylate: Yield 750 mg; 72%. Rt


7.30 (2 H, d, J = 8.42 Hz), 7.24 (2 H, d, J = 8.42 Hz), 4.39 (2 H, q, J = 6.95 Hz), 4.33 (1 H, q, J =

6.59 Hz), 1.60 (3 H, d, J = 6.59 Hz), 1.41 (3 H, t, J = 6.95 Hz); 13C-NMR (100 MHz, CDCl3):

δ/ppm = 165.08(C), 160.22(C), 140.55(C), 134.82(CH), 133.60(C), 129.07(CH), 127.57(CH),

120.61(C), 60.53(CH2), 58.25(CH), 24.40(CH3), 14.36(CH3). IR (neat) ν 2978(w), 1656(s),

1530(s), 1490(m), 1455(m), 1419(s), 1381(m), 1353(w), 1333(w), 1301(w), 1235(s), 1211(m),

1183(s), 1132(s), 1092(s), 1027(m), 1012(s), 957(w), 924(w), 860(w), 828(s), 757(m), 735(m),

701(w), 666(w); cm-1. HRMS calculated for C14H15ClN2O2SNa 333.0440; found 333.0449. αD =

+237.2, c = 1.015, CHCl3.

S

N

HN

EtO

O

Cl

(R)-Ethyl 5-(1-(4-chlorophenyl)ethylamino)thiazole-4-carboxylate: Experimental data

consistant with (S)-Ethyl 5-(1-(4-chlorophenyl)ethylamino)thiazole-4-carboxylate Yield 800 mg;

76%. αD = -236.8, c = 1.020, CHCl3.

S

N

NH

OAcO

AcOOAc

OAc O

OEt

(2R,3R,4S,5S,6R)-2-(Acetoxymethyl)-6-(4-(ethoxycarbonyl)thiazol-5-ylamino)tetrahydro-

2H-pyran-3,4,5-triyl triacetate (14): Yield 1140 mg; 85%. Rt 4.14, M+H m/z = 503.5; 1H-NMR

(400 MHz, CDCl3): δ/ppm = 8.01 (1 H, s), 7.99 (1 H, s), 5.34 (1 H, ap. t, J = 9.51 Hz), 5.12 (1 H,

ap. t, J = 9.10 Hz), 5.06 (1 H, ap. t, J = 9.51 Hz), 4.55 (1 H, ap. dd, J = 8.26, 8.77 Hz), 4.40 (2 H,

m), 4.26 (1 H, dd, J = 5.10, 12.40 Hz), 4.12 (1 H, dd, J = 2.40, 12.40 Hz), 3.80 (1 H, ddd, J =

2.40, 5.10, 9.80 Hz), 2.04 (3 H, s), 2.03 (3 H, s), 2.01 (3 H, s), 2.00 (3 H, s), 1.35 (3 H, t, J = 7.12

Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm = 170.47(C), 170.07(C), 169.98(C), 169.34(C),

163.99(C), 157.00(C), 136.98(CH), 124.05(C), 86.99(CH), 73.22(CH), 72.53(CH), 70.58(CH),

68.38(CH), 61.74(CH2), 60.90(CH2), 20.66(CH3), 20.52(CH3), 20.50(CH3), 20.48(CH3),

14.34(CH3). IR (neat) ν 1742(s), 1675(m), 1539(m), 1442(w), 1411(w), 1382(m), 1218(s),

1189(m), 1092(m), 1033(s), 909(w) cm-1. HRMS calculated for C20H26N2O11SNa 525.1155;

found 525.1140.

S

N

NH

OPhOCO

PhOCOOCOPh

OCOPh O

OEt

(2R,3R,4S,5S,6R)-2-(Benzoyloxymethyl)-6-(4-(ethoxycarbonyl)thiazol-5-

ylamino)tetrahydro-2H-pyran-3,4,5-triyl tribenzoate: Yield 2026 mg; 80%. Rt 5.35, M+H m/z

= 751.7; 1H-NMR (400 MHz, CDCl3): δ/ppm = 8.26 (1 H, d, J = 7.86 Hz), 8.01 (2 H, m), 7.94 (4

H, m), 7.83 (3 H, m), 7.52 (3 H, m), 7.38 (7 H, m), 7.26 (2 H, m), 6.08 (1 H, ap. t, J = 9.64 Hz),

5.69 (1 H, ap. t, J = 9.73 Hz), 5.66 (1 H, ap. t, J = 8.14 Hz), 4.90 (1 H, ap. dd, J = 8.00, 8.84 Hz),

4.63 (1 H, dd, J = 2.96, 12.20 Hz), 4.50 (1 H, dd, J = 6.15, 12.20 Hz), 4.38 (2 H, dq, J = 0.96,

7.16 Hz), 4.28 (1 H, m), 1.36 (3 H, t, J = 7.16 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm =

166.03(C), 165.75(C), 165.19(C), 163.71(C), 156.76(C), 136.85(CH), 133.69(CH), 133.59(CH),

133.42(CH), 133.21(CH), 130.20(C), 130.01(CH), 129.84(CH), 129.79(CH), 129.71(CH),

128.45(CH), 128.41(CH), 128.36(CH), 128.35(CH), 124.10(C), 87.39(CH), 73.62(CH),

72.75(CH), 71.45(CH), 69.59(CH), 63.04(CH2), 60.86(CH2), 14.47(CH3). IR (neat) ν 1718(s),

1672(w), 1535(w), 1451(w), 1315(w), 1248(s), 1176(w), 1140(w), 1088(s), 1067(s), 1025(s),

976(w), 735(w), 706(s), 686(m) cm-1. HRMS calculated for C40H35N2O11S 751.1941; found

751.1956.

S

N

PhOCO OCOPh

OPhOCO

EtO

O

HN

(2R,3S,4S,5R)-2-(Benzoyloxymethyl)-5-(4-(ethoxycarbonyl)thiazol-5-

ylamino)tetrahydrofuran-3,4-diyl dibenzoate: Yield 1871 mg; 90%. Rt 5.22, M+H m/z =

617.5; 1H-NMR (400 MHz, CDCl3): δ/ppm = 8.78 (1 H, d, J = 7.03 Hz), 8.19 (2 H, m), 8.07 (3

H, m), 7.96 (2 H, m), 7.55 (3 H, m), 7.40 (6 H, m), 5.89 (1 H, dd, J = 2.61, 6.41 Hz), 5.73 (1 H,

m), 5.64 (1 H, dd, J = 5.78, 7.10 Hz), 4.72 (1 H, dd, J = 4.09, 12.86 Hz), 4.63 (2 H, m), 4.38 (2


165.69(C), 164.94(C), 164.53(C), 157.91(C), 136.61(CH), 133.74(CH), 133.61(CH),

133.33(CH), 130.31(CH), 130.05(CH), 129.70(CH), 129.42(C), 128.58(CH), 128.50(CH),

128.39(CH), 122.99(C), 87.00(CH), 80.51(CH), 71.67(CH), 70.57(CH), 64.04(CH2),

60.61(CH2), 14.44(CH3). IR (neat) ν 1721(s), 1666(m), 1601(w), 1533(m), 1451(m), 1430(w),

1408(w), 1382(w), 1315(w), 1263(s), 1178(m), 1095(s), 1069(s), 1024(s), 939(w), 863(w),

840(w), 768(w), 735(m), 710(s), 686(m), 672(w) cm-1. HRMS calculated for C32H28N2O9SNa

639.1413; found 639.1420.

N

N

SCl

EtO

O

Br

Ethyl 1-(4-bromophenyl)-5-(chloromethylthio)-1H-imidazole-4-carboxylate (6a): Yield 196

mg; 15%. Rt 4.50, M+H m/z = 377.0; 1H-NMR (400 MHz, CDCl3): δ/ppm = 7.77 (1 H, s), 7.67

(2 H, d, J = 8.78 Hz), 7.23 (2 H, d, J = 8.78 Hz), 4.91 (2 H, s), 4.40 (2 H, q, J = 7.32 Hz), 1.42 (3

H, t, J = 7.32 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm = 162.63(C), 139.77(CH), 137.96(C),

134.09(C), 133.03(CH), 129.24(CH), 127.94(C), 124.28(C), 61.65(CH2), 50.56(CH2),

14.75(CH3). IR (neat) ν 1706(m), 1490(s), 1313(m), 1247(s), 1187(s), 1070(w), 1046(s),

1010(w), 957(m), 861(w), 828(m), 787(w), 716(m), 661(m); cm-1. HRMS calculated for

C13H13BrClN2O2S 374.9570; found 374.9565.

N

N

SCl

EtO

O

Cl

5-Chloromethylsulfanyl-1-(4-chlorophenyl)-1H-imidazole-4-carboxylic acid ethyl ester

(6b): Yield 515 mg; 46%. Rt 4.49, M+H m/z = 331.4; 1H-NMR (400 MHz, CDCl3): δ/ppm = 7.77

(1 H, s), 7.49 (2 H, d, J = 8.78 Hz), 7.31 (2 H, d, J = 8.78 Hz), 4.91 (2 H, s), 4.42 (2 H, q, J =

7.32 Hz), 1.42 (3 H, t, J = 7.32 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm = 162.21(C),

139.42(CH), 137.49(C), 135.84(C), 133.16(C), 129.60(CH), 128.56(CH), 127.59(C),

61.23(CH2), 50.13(CH2), 14.36(CH3). IR (neat) ν 1707(s), 1495(s), 1406(w), 1380(w), 1313(m),

1249(s), 1189(s), 1092(m), 1050(s), 1012(w), 959(m), 835(m), 788(w), 718(m), 662(w); cm-1.

HRMS calculated for C13H12Cl2N2O2SNa 352.9894; found 352.9880.

S

N

SS

N

S

O

EtOO

OEt

Diethyl 5,5'-methylene-bis(sulfanediyl)dithiazole-4-carboxylate: Yield 1315 mg; 100%. Rt

4.10, M+H m/z = 391.2; 1H-NMR (400 MHz, CDCl3): δ/ppm = 8.71 (2 H, s), 4.56 (2 H, s), 4.50

(4 H, q, J = 7.32 Hz), 1.42 (6 H, t, J = 7.32 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm =

161.80(C), 151.01(CH), 142.58(C), 142.02(C), 61.77(CH2), 43.40(CH2), 14.32(CH3). IR (neat) ν

2975(w), 2905(w), 1687(s), 1435(s), 1389(w), 1366(w), 1323(s), 1250(s), 1177(s), 1114(w),

1095(w), 1041(s), 949(w), 933(w), 843(m), 779(m), 715(w) cm-1. HRMS calculated for

C13H15N2O4S4 390.9915; found 390.9919.

N

N

SS

N

N

O

EtOO

OEt

BrBr

Diethyl 5,5'-methylene-bis(sulfanediyl)-bis(1-(4-Bromophenyl)-1H-imidazole-4-carboxylate)

(7): Yield 112 mg; 5%. Rt 4.71, M+H m/z = 667.6; 1H-NMR (400 MHz, CDCl3): δ/ppm = 7.51 (2

H, s), 7.56 (4 H, d, J = 8.78 Hz), 6.96 (4 H, d, J = 8.78 Hz), 4.33 (4 H, q, J = 7.32 Hz), 4.22 (2 H,

s), 1.34 (6 H, t, J = 7.32 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm = 160.11(C), 136.84(CH),

135.01(C), 131.79(C), 130.77(CH), 127.03(C), 126.37(CH), 121.79(C), 59.23(CH2), 39.79(CH2),

12.53(CH3). IR (neat) ν 1708(m), 1491(s), 1380(w), 1363(w), 1313(m), 1248(s), 1187(m),

1100(w), 1070(w), 1047(m), 1010(w), 957(m), 829(m), 786(w), 730(w), 710(w), 664(w) cm-1.

HRMS calculated for C25H23Br2N4O4S2 664.9560; found 664.9527.

S

N

HN

SO

Tol

O

Cl

(4-Chlorophenyl)-[4-(toluene-4-sulfonyl)thiazol-5-yl]amine: Yield 1180 mg; 96%. Rt 4.86,


H, d, J = 8.48 Hz), 7.33 (4 H, m), 7.17 (2 H, d, J = 8.48 Hz), 2.41 (3 H, s); 13C-NMR (100 MHz,

CDCl3): δ/ppm = 151.10(C), 144.58(C), 139.42(C), 138.16(C), 137.08(CH), 129.84(CH × 2),

129.59(C), 129.43(C), 127.47(CH), 120.42(CH), 21.62(CH3). IR (neat) ν 3283(w), 1584(m),

1541(m), 1478(m), 1431(m), 1310(m), 1299(m), 1289(m), 1215(w), 1180(w), 1132(s), 1077(m),

1021(w), 810(s), 777(w), 735(w), 704(m), 677(s) cm-1. HRMS calculated for C16H13ClN2O2S2Na

387.0005; found 387.0019.

S

N

HN

SO

Tol

O

Cl

Cl

(3,4-Dichlorophenyl)-[4-(toluene-4-sulfonyl)thiazol-5-yl]amine: Yield 1240 mg; 92%. Rt


7.90 (2 H, d, J = 8.18 Hz), 7.41 (1 H, m), 7.35 (1 H, m), 7.32 (2 H, d, J = 8.18 Hz), 7.08 (1 H,

m), 2.41 (3 H, s); 13C-NMR (100 MHz, CDCl3): δ/ppm = 149.86(C), 144.77(C), 140.20(C),

137.88(C), 137.77(CH), 133.66(C), 131.32(CH), 130.40(C), 129.88(CH), 128.24(C),

127.53(CH), 120.35(CH), 118.16(CH), 21.64(CH3). IR (neat) ν 3281(w), 1584(m), 1540(m),

1478(w), 1430(m), 1325(w), 1309(w), 1299(w), 1289(m), 1214(w), 1180(w), 1158(w), 1131(s),

1076(m), 1039(w), 1021(w), 940(w), 896(w), 810(s), 777(w), 749(w), 737(w), 704(m), 677(s)

cm-1. HRMS calculated for C16H12Cl2N2O2S2Na 420.9615; found 420.9621.

S

N

HN

SO

Tol

O

OMe

(2-Methoxyphenyl)-[4-(toluene-4-sulfonyl)thiazol-5-yl]amine: Yield 1090 mg; 90%. Rt 4.75,


H, d, J = 8.13 Hz), 7.34 (1 H, m), 7.30 (2 H, d, J = 8.13 Hz), 7.05 (1 H, m), 6.97 (2 H, m), 3.97

(3 H, s), 2.40 (3 H, s); 13C-NMR (100 MHz, CDCl3): δ/ppm = 150.60(C), 149.47(C), 144.22(C),

138.71(C), 136.56(CH), 130.37(C), 129.74(CH), 129.48(C), 127.36(CH), 123.90(CH),

120.81(CH), 115.66(CH), 111.01(CH), 50.01(CH3), 21.59(CH3). IR (neat) ν 1600(w), 1547(s),

1493(w), 1463(w), 1443(w), 1423(w), 1300(m), 1244(m), 1137(m), 1116(w), 1081(w), 1026(w),

814(w), 744(w), 676(m) cm-1. HRMS calculated for C17H16N2O3S2Na 383.0500; found

383.0493.

S

N

HN

SO

Tol

O

F

(3-Fluorophenyl)-[4-(toluene-4-sulfonyl)thiazol-5-yl]amine: Yield 1023 mg; 87%. Rt 4.74,


H, d, J = 8.18 Hz), 7.33 (1 H, m), 7.32 (2 H, d, J = 8.18 Hz), 7.01 (1 H, m), 6.97 (1 H, m), 6.82

(1 H, m), 2.41 (3 H, s); 13C-NMR (100 MHz, CDCl3): δ/ppm = 163.52(C, d, J = 247.13 Hz),

150.11(C), 144.64(C), 142.22(C, d, J = 9.95 Hz), 138.08(C), 137.51(CH), 131.13(CH, d, J =

9.12 Hz), 129.98(C), 129.85(CH), 127.51(CH), 114.28(CH, d, J = 2.49 Hz), 110.02(CH, d, J =

20.73 Hz), 105.76(CH, d, J = 25.71 Hz), 21.63(CH3). IR (neat) ν 3305(w), 1619(w), 1594(m),

1557(s), 1496(m), 1447(m), 1420(m), 1315(m), 1298(m), 1290(s), 1248(m), 1184(m), 1135(s),

1119(m), 1079(m), 959(w), 912(w), 859(w), 848(w), 817(s), 796(w), 770(m), 759(w), 735(w),

704(m), 675(s) cm-1. HRMS calculated for C16H13FN2O2S2Na 371.0300; found 371.0296.

S

N

HN

SO

Tol

O

CF3

[4-(Toluene-4-sulfonyl)thiazol-5-yl]-(3-trifluoromethylphenyl)amine: Yield 1250 mg; 93%.

Rt 4.94, M+H m/z = 399.4; 1H-NMR (400 MHz, CDCl3): δ/ppm = 9.03 (1 H, br. s), 8.02 (1 H, s),

7.92 (2 H, d, J = 8.48 Hz), 7.49 (2 H, m), 7.39 (2 H, m), 7.32 (2 H, d, J = 8.48 Hz), 2.41 (3 H, s); 13C-NMR (100 MHz, CDCl3): δ/ppm = 149.92(C), 144.73(C), 141.25(C), 137.96(C),

137.57(CH), 132.29(C, q, J = 33.17 Hz), 130.48(CH), 130.42(C), 129.88(CH), 127.54(CH),

123.44(C, q, J = 272.7 Hz), 121.65(CH, m), 120.71(CH, q, J = 3.3 Hz), 115.20(CH, q, J = 4.14

Hz), 21.62(CH3). IR (neat) ν 3320(w), 1617(w), 1565(s), 1505(m), 1450(w), 1424(s), 1336(s),

1311(m), 1288(s), 1216(w), 1185(m), 1172(s), 1140(s), 1122(s), 1081(s), 1070(m), 901(w),

864(w), 819(m), 811(m), 793(w), 778(m), 707(w), 699(w), 690(w), 678(s) cm-1. HRMS

calculated for C17H13F3N2O2S2Na 421.0268; found 421.0281.

S

N

HN

SO

Tol

O

CF3F3C

(3,5-Bis-trifluoromethylphenyl)-[4-(toluene-4-sulfonyl)thiazol-5-yl]amine: Yield 1510 mg;

96%. Rt 5.15, M+H m/z = 467.5; 1H-NMR (400 MHz, CDCl3): δ/ppm = 9.22 (1 H, br. s), 8.12 (1

H, s), 7.93 (2 H, d, J = 8.48 Hz), 7.65 (2 H, m), 7.58 (1 H, m), 7.35 (2 H, d, J = 8.48 Hz), 2.43 (3

H, s); 13C-NMR (100 MHz, CDCl3): δ/ppm = 148.05(C), 145.05(C), 142.05(C), 138.61(CH),

137.51(C), 133.34(C, q, J = 34.00 Hz), 132.14(C), 129.94(CH), 127.69(CH), 122.83(C, J =

272.83 Hz), 117.58(CH, m), 116.92(CH, m), 21.63(CH3). IR (neat) ν 3297(w), 1575(s),

1479(m), 1466(w), 1429(m), 1388(s), 1327(w), 1275(s), 1185(m), 1163(s), 1122(s), 1081(s),

996(w), 961(w), 904(w), 879(m), 846(m), 811(s), 779(w), 741(w), 704(m), 693(w), 669(s) cm-1.

HRMS calculated for C18H13F6N2O2S2 467.0323; found 467.0341.

S

N

S

SO

Tol

O

O

1-Phenyl-2-[4-(toluene-4-sulfonyl)thiazol-5-ylsulfanyl]ethanone: Yield 1120 mg; 85%. Rt

4.61, M+H m/z = 390.4; 1H-NMR (400 MHz, CDCl3): δ/ppm = 8.62 (1 H, s), 7.97 (2 H, d, J =

8.42 Hz), 7.94 (2 H, m), 7.62 (1 H, m), 7.49 (2 H, m), 7.29 (2 H, d, J = 8.42 Hz), 4.53 (2 H, s),

2.40 (3 H, s); 13C-NMR (100 MHz, CDCl3): δ/ppm = 192.36(C), 152.76(CH), 151.59(C),

144.97(C), 138.89(C), 137.27(C), 134.97(C), 134.08(CH), 129.79(CH), 128.93(CH),

128.56(CH), 128.24(CH), 44.94(CH2), 21.65(CH3). IR (neat) ν 1679(m), 1595(w), 1448(w),

1403(m), 1320(s), 1304(m), 1291(m), 1199(s), 1144(s), 1085(m), 1033(w), 1000(w), 813(m),

751(w), 735(m), 704(w), 684(s) cm-1. HRMS calculated for C18H16NO3S3 390.0272; found

390.0286.

S

N

S

EtO

O

S

N

S

EtO

O

+

MeO

O

O OMe

5-(2-Methoxycarbonyl-vinylsulfanyl)thiazole-4-carboxylic acid ethyl ester: Solvent: 9/1

MeCN/THF. Yield 895 mg; 97% (Trans + Cis). Rt 4.05, M+H m/z = 274.7; Trans: Cis = 1: 2.7 1H-NMR (400 MHz, CDCl3): δ/ppm = 8.81 (1 H, s, Trans), 8.78 (1 H, s, Cis), 7.73 (1 H, d, J =

15.17 Hz, Trans), 7.25 (1 H, d, J = 9.98 Hz, Cis), 6.15 (1 H, d, J = 15.17 Hz, Trans), 6.07 (1 H,

d, J = 9.98 Hz, Cis), 4.45 (4 H, q, J = 7.14 Hz, Cis + Trans), 3.81 (3 H, s, Cis), 3.77 (3 H, s,

Trans), 1.44 (3 H, t, J = 7.14 Hz, Cis + Trans); 13C-NMR (100 MHz, CDCl3): δ/ppm = 166.36(C,

Cis), 164.84(C, Trans), 161.39(C, Trans), 161.23(C, Cis), 152.11(CH, Trans), 151.98(CH, Cis),

146.61(CH, Cis), 143.95(C, Cis), 143.23(C, Trans), 142.85(CH, Trans), 141.74(C, Cis),

138.75(C, Trans), 120.29(CH, Trans), 115.83(CH, Cis), 61.93(CH2, Trans), 61.85(CH2, Cis),

51.92(CH3, Trans), 51.76(CH3, Cis), 14.27(CH3, Cis + Trans). IR (neat) ν 1696(s), 1586(m),

1459(m), 1433(m), 1390(w), 1364(w), 1317(m), 1257(s), 1223(s), 1163(s), 1095(w) 1041(m),

1020(m), 940(m), 846(m), 801(m), 780(m), 697(m), 667(w) cm-1. HRMS calculated for

C10H11NO4S2Na 296.0027; found 296.0025.

S

N

S

EtO

O

O Ph

5-(3-Oxo-3-phenyl-propylsulfanyl)-thiazole-4-carboxylic acid ethyl ester: Solvent: 9/1

MeCN/THF. Yield 1040 mg; 96%. Rt 4.43, M+H m/z = 322.7; 1H-NMR (400 MHz, CDCl3):

δ/ppm = 8.66 (1 H, s), 7.97 (2 H, m), 7.62 (1 H, m), 7.50 (2 H, m), 4.45 (2 H, q, J = 7.14 Hz),

3.47 (4 H, m), 1.44 (3 H, t, J = 7.14 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm = 196.80(C),

162.12(C), 149.01(CH), 146.92(C), 140.16(C), 136.11(C), 133.63(CH), 128.77(CH),

128.00(CH), 61.49(CH2), 37.53(CH2), 31.24(CH2), 14.37(CH3). IR (neat) ν 1716(m), 1682(s),

1596(w), 1579(w), 1448(m), 1435(s), 1389(w), 1353(m), 1320(m), 1259(s), 1232(m), 1180(s)

1159(m), 1095(w), 1046(m), 1025(m), 1001(w), 970(m), 941(w), 843(m), 776(m), 748(m),

688(m) cm-1. HRMS calculated for C15H15NO3S2Na 344.0391; found 344.0385.

S

N

SO

Br

EtO

O

5-[2-(4-Bromophenyl)-2-oxo-ethylsulfanyl]-thiazole-4-carboxylic acid ethyl ester: Solvent:

9/1 MeCN/THF. Yield 1240 mg; 95%. Rt 4.57, M-H m/z 386.3; 1H-NMR (400 MHz, CDCl3):

δ/ppm = 8.60 (1 H, s), 7.80 (2 H, d, J = 8.59 Hz), 7.62 (2 H, d, J = 8.59 Hz), 4.45 (2 H, s), 4.40

(2 H, q, J = 7.14 Hz), 1.39 (3 H, t, J = 7.14 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm =

191.44(C), 161.89(C), 149.96(CH), 143.70(C), 141.88(C), 133.66(C), 132.25(CH), 130.02(CH),

129.39(C), 61.57(CH2), 43.64(CH2), 14.33(CH3). IR (neat) ν 1680(s), 1584(m), 1452(w),

1437(m), 1396(w), 1373(w), 1321(m), 1293(w), 1256(s), 1210(w), 1185(s), 1070(w), 1051(m),

1025(w), 1009(w), 985(m), 846(w), 810(m), 777(m), 733(w) cm-1. HRMS calculated for

C14H13BrNO3S2 385.9496; found 385.9514.

S

N

HS

EtO

O

Ethyl 5-mercaptothiazole-4-carboxylate (10): Solvent: 9/1 MeCN/THF. Yield 574 mg; 90%.

Rt 4.29, M+H m/z = 190.1; 1H-NMR (400 MHz, CDCl3): δ/ppm = 8.66 (1 H, s), 5.68 (1 H, br. s),

4.47 (2 H, q, J = 7.32 Hz), 1.45 (3 H, t, J = 7.32 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm =

162.12(C), 151.29(CH), 148.77(C), 140.67(C), 61.13(CH2), 14.30(CH3). IR (neat) ν 2982(w),

1727(m), 1687(s), 1468(m), 1433(s), 1367(w), 1325(s), 1265(s), 1189(s), 1037(m), 847(w),

779(w), 735(w) cm-1. HRMS calculated for C6H8NO2S2 189.9888; found 189.9865.

S

N

S

EtO

O

Me

Ethyl 5-(methylthio)thiazole-4-carboxylate: Solvent: 9/1 MeCN/THF. Yield 596 mg; 87%. Rt

3.87, M+H m/z = 204.3; 1H-NMR (400 MHz, CDCl3): δ/ppm = 8.55 (1 H, s), 4.36 (2 H, q, J =

7.14 Hz), 2.54 (3 H, s), 1.37 (3 H, t, J = 7.14 Hz); 13C-NMR (100 MHz, CDCl3): δ/ppm =

162.16(C), 149.95(C), 148.50(CH), 138.66(C), 61.30(CH2), 19.99(CH3), 14.12(CH3). IR (neat) ν

3066(w), 2976(w), 1698(s), 1475(w), 1426(s), 1366(m), 1332(m), 1317(m), 1255(s), 1170(s),

1044(s), 1022(m), 956(w), 931(w), 849(s), 776(m), 731(w) cm-1. HRMS calculated for

C7H10NO2S2 204.0153; found 204.0146.

Appendix of X-ray-structures

Crystal structures have been deposited at the Cambridge Crystallographic Data Centre (CCDC)

under the deposition numbers 657043 to 657054. We wish to thank J. E. Davies for determining

the crystal structures of all the compounds presented and thank the EPSRC for financial

contribution towards the purchase of the diffractometer.

X-ray obtained from crystal of 5-(3-methoxyphenylamino)thiazole-4-carboxylic acid ethyl

ester

File reference: CCDC 657043

Authors: L. Tamborini, S. V. Ley

Journal: J. Combinatorial Chemistry (1343)

Formula: C13 H14 N2 O3 S1

Unit cell parameters: a 26.7716(10) b 13.1113(4) c 7.6759(2) space group Pccn

X-ray obtained from crystal of ethyl 5-(2-(4-bromophenyl)-2-oxoethylthio)-1-(3-

methoxyphenyl)-1H-imidazole-4-carboxylate




Formula: C21 H19 Br1 N2 O4 S1

Unit cell parameters: a 8.66240(10) b 8.8315(2) c 13.5861(3) alpha 93.0640(10) beta 98.7650(10) gamma

91.6330(10) space group P-1

X-ray structure obtained from crystal of 5-[2-(4-cyanophenyl)-2-oxo-ethylsulfanyl]-1-(3,4-

dichlorophenyl)-1H-imidazole-4-carboxylic acid ethyl ester




Formula: C21 H15 Cl2 N3 O3 S1

Unit cell parameters: a 9.57050(10) b 9.95840(10) c 12.0088(2) alpha 77.3540(10) beta 77.0920(10) gamma

68.3560(10) space group P-1

X-ray structure obtained from crystal of 5-(4-methoxyphenylamino)thiazole-4-carboxylic

acid ethyl ester





Unit cell parameters: a 8.2285(2) b 18.0070(5) c 8.8481(3) beta 94.051(1) space group P21/c

X-ray structure obtained from crystal of (S)-ethyl 5-(1-(4-

Chlorophenyl)ethylamino)thiazole-4-carboxylate





Unit cell parameters: a 7.73240(10) b 12.6496(2) c 15.1455(3) space group P212121

X-ray structure obtained from crystal of 5-[2-(4-bromophenyl)-2-oxo-ethylsulfanyl]-1-(3-

fluorophenyl)-1H-imidazole-4-carboxylic acid ethyl ester




Formula: C20 H16 Br1 F1 N2 O3 S1

Unit cell parameters: a 9.5833(2) b 9.6839(2) c 11.5109(3) alpha 69.9570(10) beta 84.0560(10) gamma 79.2590(10)

space group P-1

X-ray structure obtained from crystal of 5-(2-methoxyphenylamino)thiazole-4-carboxylic

acid ethyl ester





Unit cell parameters: a 13.1196(2) b 5.09740(10) c 20.2202(4) beta 105.8130(10) space group P21/n

X-ray structure obtained from crystal of 1-(4-bromophenyl)-5-[2-(4-bromophenyl)-2-oxo-

ethylsulfanyl]-1H-imidazole-4-carboxylic acid ethyl ester




Formula: C20 H16 Br2 N2 O3 S1

Unit cell parameters: a 8.5069(2) b 9.0530(2) c 13.5500(3) alpha 78.8500(10) beta 76.5530(10) gamma 89.6500(10)

space group P-1

X-ray structure obtained from crystal of 5-chloromethylsulfanyl-1-(4-chlorophenyl)-1H-

imidazole-4-carboxylic acid ethyl ester





Unit cell parameters: a 7.0766(2) b 14.0793(4) c 7.4599(3) beta 100.9100(10) space group P21

X-ray structure obtained from crystal of (3-fluorophenyl)-[4-(toluene-4-sulfonyl)-thiazol-5-

yl]amine




Formula: C16 H13 F1 N2 O2 S2


X-ray structure obtained from crystal of (4-chlorophenyl)-[4-(toluene-4-sulfonyl)-thiazol-5-

yl]amine


Authors: L. Tamborini, S.V.Ley




X-ray structure obtained from crystal of

(2-Methoxyphenyl)-[4-(toluene-4-sulfonyl)-thiazol-5-yl]amine





Unit cell parameters: a 32.5334(3) b 6.8076(1) c 15.0129(1) space group Pbcn

a bifocated pathway to thiazoles and imidazoles using a … · 2015-12-10 · vineland, nj, usa) or...

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