156
T. Masquelin, D. Obrecht / Tetrahedron 57 (2001) 153±156
NMR (400 MHz, d6-DMSO): d 187.3 (s); 166.07 (s);
158.42 (s); 140.29 (s); 137.50 (s); 134.75 (s); 131.14
(2£d); 131.06 (2£d); 130.12 (2£d); 129.61 (2£d);
129.08 (d); 128.05 (2£d); 125.63 (s); 123.34 (d); 121.55
(s); 118.61 (2£d). IR (KBr): 3285w, 2924w, 1611m,
1507s, 1254s, 1119m, 747m. MS: 434 [M1] (100%).
7.63 (d, J8.75 Hz, 2H arom.); 7.63±7.60 (d, J7.77 Hz,
2H arom.); 7.39±7.33 (t, J7.52 Hz, 2H arom.); 7.09±7.04
(t, J7.52 Hz, 1H arom.). IR (KBr): 3414w, 3271w, 1592s,
1546s, 1431s, 755m, 695m. MS: 374 [M1H]1 (100%).
1.1.17. 2-Phenylamino-4-amino-5-[(4-¯uorophenyl)-
carbonyl]thiazole (10d). According to Method D with 5c
(0.4 g, 1.19 mmol), 6e (0.284 g, 1.43 mmol) and DBU
(0.372 ml, 2.50 mmol): 0.367 g (99%) of 10d. Yellow
1.1.12. 2-Phenylamino-4-(thiophen-2-yl)-5-phenylcarbonyl-
thiazole (9c). According to Method C with 4b (0.20 g,
0.765 mmol), 6c (0.160 g, 0.803 mmol) and DBU (0.239
ml, 1.606 mmol): 0.205 g (73%) of 9c. Yellow solid. Mp
135±1388C. 1H NMR (250 MHz, d6-DMSO): 10.89 (s, NH);
7.71±7.60 (m, 6H arom.); 7.59±7.36 (m, 5H arom.); 7.11±
7.04 (t, J7.35 Hz, 1H arom.); 6.97±6.94 (t, J4.45 Hz, 1H
arom.). IR (KBr): 3162w, 2924w, 1609m, 1495s, 1292s,
1119m, 858m, 767m, 693. MS: 362 [M1] (100%).
1
solid. Mp 190±1928C. H NMR (250 MHz, d6-DMSO):
10.82 (s, NH); 8.25 (br.s, NH2); 7.77±7.71 (dd, J14.32,
8.77 Hz, 2H arom.); 7.63±7.60 (d, J7.77 Hz, 2H arom.);
7.39±7.27 (m, 4H arom.); 7.09±7.04 (t, J7.52 Hz, 1H
arom.). IR (KBr): 3418w, 3197w, 1599s, 1550s, 1431m,
849m, 760m, 694m. MS: 314 [M1H]1 (100%).
Acknowledgements
1.1.13. 2-Phenylamino-4-(thiophen-2-yl)-5-[(4-bromo-
phenyl)carbonyl]thiazole (9d). According to Method C
with 4b (0.20 g, 0.765 mmol), 6b (0.223 g, 0.803 mmol)
and DBU (0.239 ml, 1.606 mmol): 0.23 g (74%) of 9d.
We gratefully thank our colleagues from F. HoffmannÐla
Roche AGÐfor analytical support.
1
Yellow solid. Mp 132±1348C. H NMR (250 MHz, d6-
DMSO): 10.95 (s, NH); 7.68±7.58 (m, 8H arom.); 7.43±
7.36 (m, 2H arom.); 7.11±7.04 (t, J7.35 Hz, 1H arom.);
6.98±6.94 (m, 1H arom.). IR (KBr): 3276w, 2924w, 1614m,
1525s, 1290s, 1011m, 791m, 767m, 714. MS: 442 [M1H]1
(100%).
References
1. Zabriskie, T. M.; Mayne, C. L.; Ireland, C. M. J. Am. Chem.
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Takahashi, K.; Nakano, H. J. J. Antibiot. 1988, 42, 1768±1774.
3. Crews, P.; Kakou, Y.; Quinoa, E. J. Am. Chem. Soc. 1988,
110, 4365±4368.
1.1.14. 2-Phenylamino-4-amino-5-cyclohexylcarbonyl-
thiazole (10a). According to Method D with 5b (0.3 g,
0.919 mmol), 6d (0.188 ml, 1.10 mmol) and DBU
(0.288 ml, 1.93 mmol): 0.180 g (65%) of 10a after FC puri-
®cation with AcOEt/CH2Cl2 [1:4]. Yellow solid. Mp 211±
2138C. 1H NMR (250 MHz, d6-DMSO): 10.68 (s, NH); 7.95
(br.s, NH2); 7.62±7.59 (d, J7.65 Hz, 2H arom.); 7.39±
7.32 (t, J7.48 Hz, 2H arom.); 7.10±7.04 (t, J7.32 Hz,
1H arom.); 2.29±2.24 (t, J10.81 Hz, 1H aliph.); 1.75±
1.62 (m, 5H aliph.); 1.41±1.13 (m, 5H aliph.). 13C NMR
(400 MHz, d6-DMSO): d 191.9 (s); 165.66 (s); 164.16 (s);
140.22 (s); 129.56 (2£d); 123.61 (d); 119.31 (2£d); 50.71 (s);
29.31 (2£t); 26.01 (t); 25.80 (2£t). IR (KBr): 3418w, 2930w,
1611m, 1553s, 1451s, 783m, 700m. MS: 301 [M1] (100%).
4. Metzger, J. V. Chemistry of Heterocyclic Compounds; Wiley:
New York, 1979; p 34.
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1.1.15. 2-Phenylamino-4-amino-5-[(4-methoxyphenyl)-
carbonyl]thiazole (10b). According to Method D with 5c
(0.4 g, 1.19 mmol), 6a (0.327 g, 1.43 mmol) and DBU
(0.372 ml, 2.50 mmol): 0.315 g (90%) of 10b after FC puri-
®cation with AcOEt/hexane [1:1]. Yellow solid. Mp 231±
2338C. 1H NMR (250 MHz, d6-DMSO): 10.76 (s, NH); 8.16
(br.s, NH2); 7.69±7.65 (d, J8.75 Hz, 2H arom.); 7.63±
7.60 (d, J7.77 Hz, 2H arom.); 7.39±7.33 (t, J7.52 Hz,
2H arom.); 7.09±7.04 (t, J7.52 Hz, 1H arom.); 7.03±6.99
(d, J8.75 Hz, 2H arom.); 3.81 (s, 3H aliph.). IR (KBr):
3413w, 3201w, 1587s, 1522s, 1251m, 761m, 694m. MS:
326 [M1H]1 (100%).
12. Hermkens, P. H. H.; Ottenheijm, H. C. J.; Rees, D. Tetrahedron
1996, 52, 4527±4554.
13. Obrecht, D.; Villargordo, J. M. Solid-Supported Combinatorial
and Parallel Synthesis of Small-Molecular-Weight Compound
Libraries; Elsevier: Oxford, 1998; p 17.
14. Chucholowski, A.; Masquelin, T.; Obrecht, D.; Stadlwieser,
J.; Villalgordo, J. M. Chimia 1996, 50, 525±530.
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Y. Helv. Chim. Acta 1998, 81, 646±660.
16. Obrecht, D.; Gerber, F.; Sprenger, D.; Masquelin, T. Helv.
Chim. Acta 1997, 80, 531±537.
1.1.16. 2-Phenylamino-4-amino-5-[(4-bromophenyl)-
carbonyl]thiazole (10c). According to Method D with 5c
(0.4 g, 1.19 mmol), 6b (0.397 g, 1.43 mmol) and DBU
(0.372 ml, 2.50 mmol): 0.373 g (84%) of 10c after FC puri-
®cation with AcOEt/Hexane [1:1]. Orange solid. Mp 205±
2078C. 1H NMR (250 MHz, d6-DMSO): 10.87 (s, NH); 8.25
(br.s, NH2); 7.70±7.67 (d, J8.75 Hz, 2H arom.); 7.67±
17. Masquelin, T.; Delgado, Y.; Baumle, V. Tetrahedron Lett.
1998, 39, 5725±5726.
18. Obrecht, D.; Abrecht, C.; Grieder, F.; Villalgordo, J.-M. Helv.
Chim. Acta 1997, 80, 65±72.
19. Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43,
2923±2925.