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M. B. Nolt et al. / Tetrahedron 62 (2006) 4698–4704
4.4.4. ( )-Ethyl 5-(2,3-dihydro-1H-inden-1-ylamino)-
2-phenyloxazole-4-carboxylate (13d). 1H NMR (400 MHz,
CDCl3) d 7.94–7.97 (m, 2H), 7.22–7.44 (m, 7H), 6.55
(d, J¼8.4 Hz, 1H), 5.38 (q, J¼15.6, 7.6 Hz, 1H), 4.37
(q, J¼14.4, 7.2 Hz, 2H), 3.07–3.14 (m, 1H), 2.91–2.99
(m, 1H), 2.68–2.77 (m, 1H), 2.02–2.11 (m, 1H), 1.39
(t, J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 164.3,
160.3, 150.4, 143.3, 142.4, 129.9, 128.9, 128.7, 127.2,
127.1, 125.9, 125.2, 124.2, 60.4, 59.0, 34.8, 30.4, 14.9.
HRMS calcd for C21H21N2O3 (M+H) 349.1547, found
349.1539.
HRMS calcd for C21H21N2O3 (M+H) 349.1547, found
349.1544.
4.4.10. Ethyl 5-({2-[4-(aminosulfonyl)phenyl]ethyl}-
amino)-2-phenyl-1,3-oxazole-4-carboxylate (13j). 1H
NMR (300 MHz, (CD3)2SO) d 7.72–7.73 (m, 4H), 7.43–
7.50 (m, 5H), 7.26 (s, 2H), 4.20 (q, J¼6.9 Hz, 2H), 3.67
(br s, 2H), 3.01 (t, J¼6.6 Hz, 2H), 1.25 (t, J¼6.9 Hz, 3H);
13C NMR (100 MHz, (CD3)2SO) d 163.1, 160.5, 149.2,
143.8, 142.9, 130.2, 129.9, 129.7, 127.2, 126.4, 125.6,
103.8, 59.7, 44.4, 36.1, 15.3. HRMS calcd for
C20H22N3O5S (M+H) 416.1275, found 416.1271.
4.4.5. Ethyl 5-(4-methylpiperazin-1-yl)-2-phenyloxazole-
4-carboxylate (13e). H NMR (400 MHz, CDCl3) d 7.93–
1
4.4.11. tert-Butyl 3-(4-(ethoxycarbonyl)-2-phenyloxazol-
5-ylamino)propylcarbamate (13k). H NMR (400 MHz,
1
7.96 (m, 2H), 7.40–7.43 (m, 3H), 4.38 (q, J¼14.4, 7.2 Hz,
2H), 3.77 (t, J¼4.8 Hz, 4H), 2.65 (t, J¼4.8 Hz, 4H), 2.40
(s, 3H), 1.41 (t, J¼6.8 Hz, 3H); 13C NMR (100 MHz,
CDCl3) d 162.8, 159.4, 151.2, 130.1, 128.8, 126.9, 126.1,
108.9, 60.8, 54.6, 48.1, 46.1, 14.8. HRMS calcd for
C17H22N3O3 (M+H) 316.1656, found 316.1647.
CDCl3) d 7.93–7.99 (m, 2H), 7.36–7.43 (m, 3H), 6.60 (s,
1H), 4.66 (s, 1H), 4.39 (q, J¼6.8 Hz, 2H), 3.55 (q, J¼6.8,
2H), 3.27 (q, J¼6.4 Hz, 2H), 1.86 (apparent quintet,
J¼6.6, 2H), 1.46 (s, 9H), 1.41 (t, J¼7.2 Hz, 3H); 13C
NMR (100 MHz, CDCl3) d 164.0, 160.4, 156.3, 150.0,
129.6, 128.6, 126.9, 125.6, 104.5, 60.2, 40.5, 37.6, 30.9,
28.4, 14.7. HRMS calcd for C20H28N3O5 (M+H)
390.2024, found 390.2023.
4.4.6. Ethyl 5-(2-(1,3-dioxolan-2-yl)ethylamino)-2-phe-
nyloxazole-4-carboxylate (13f). 1H NMR (400 MHz,
CDCl3) d 7.93–7.96 (m, 2H), 7.36–7.44 (m, 3H), 6.75–
6.79 (m, 1H), 5.05 (t, J¼4.2 Hz, 1H), 4.38 (q, J¼7.2 Hz,
2H), 3.99–4.07 (m, 2H), 3.88–3.96 (m, 2H), 3.67 (q,
J¼6.3 Hz, 2H), 2.07–2.13 (m, 2H), 1.39 (t, J¼7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3) d 164.1, 160.4, 150.2, 129.7,
128.8, 127.1, 125.8, 103.2, 65.3, 60.3, 38.5, 33.2, 14.8.
HRMS calcd for C17H21N2O5 (M+H) 333.1445, found
333.1439.
4.4.12. Ethyl 5-((pyrimidin-4-yl)methylamino)-2-phenyl-
oxazole-4-carboxylate (13l). H NMR (300 MHz, CDCl3)
1
d 9.23–9.24 (m, 1H), 8.74 (d, J¼5.4 Hz, 1H), 7.88–7.91
(m, 2H), 7.38–7.44 (m, 4H), 7.23–7.27 (m, 1H), 4.81 (d,
J¼5.7 Hz, 2H), 4.43 (q, J¼7.2 Hz, 2H), 1.44 (t, J¼6.9 Hz,
3H); 13C NMR (100 MHz, CDCl3) d 165.1, 164.1, 159.9,
159.0, 157.7, 150.8, 130.0, 128.9, 126.8, 125.9, 118.6,
105.7, 60.7, 47.4, 14.8. HRMS calcd for C17H17N4O3
(M+H) 325.1222, found 325.1294.
4.4.7. Ethyl 5-(2-(tert-butylthio)ethylamino)-2-phenyl-
oxazole-4-carboxylate (13g). 1H NMR (300 MHz, CDCl3)
d 7.93–7.96 (m, 2H), 7.36–7.44 (m, 3H), 6.60 (t, J¼5.6 Hz,
1H), 4.39 (q, J¼14.4, 7.2 Hz, 2H), 3.68 (q, J¼13.6, 6.8 Hz,
2H), 2.84 (t, J¼7.2 Hz, 2H), 1.41 (t, J¼7.2, 3H), 1.36
(s, 9H); 13C NMR (125 MHz, CDCl3) d 164.0, 160.1,
150.2, 129.7, 128.6, 126.8, 125.6, 104.8, 76.8, 60.3,
43.4, 42.73, 42.72, 31.1, 28.3, 14.7. HRMS calcd for
C18H25N2O3S (M+H) 349.1581, found 349.1577.
4.4.13. Ethyl 5-((pyridin-3-yl)methylamino)-2-phenyl-
oxazole-4-carboxylate (13m). 1H NMR (400 MHz,
CDCl3) d 8.68 (s, 1H), 8.58–8.59 (m, 1H), 7.89–7.92
(m, 2H), 7.71–7.74 (m, 1H), 7.39–7.41 (m, 3H), 7.31–7.34
(m, 1H), 6.72–6.75 (m, 1H), 4.69 (d, J¼6.4 Hz, 2H), 4.39
(q, J¼7.2 Hz, 2H), 1.41 (t, J¼7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3) d 164.3, 160.2, 150.7, 149.7, 149.3,
135.3, 133.3, 130.0, 128.9, 126.8, 128.9, 124.0, 105.4,
76.9, 60.6, 45.0, 14.8. HRMS calcd for C18H18N3O3
(M+H) 324.1343, found 324.1332.
4.4.8. Ethyl 5-(5-(methoxycarbonyl)pentylamino)-2-phe-
nyloxazole-4-carboxylate (13h). 1H NMR (400 MHz,
CDCl3) d 7.92–7.95 (m, 2H), 7.36–7.44 (m, 3), 6.34 (s,
1H), 4.38 (q, J¼14.4, 7.2 Hz, 2H), 3.67 (s, 3H), 3.50 (q,
J¼6.4 Hz, 2H), 2.35 (t, J¼7.6 Hz, 2H), 1.67–1.76 (m, 4H),
1.44–1.50 (m, 2H), 1.41 (t, J¼8.0 Hz, 3H); 13C NMR
(100 MHz, CDCl3) d 174.1, 160.9, 150.2, 129.8, 128.8,
127.1, 125.8, 104.6, 76.9, 60.4, 51.7, 43.2, 34.0, 30.0,
26.4, 24.7, 14.9. HRMS calcd for C19H25N2O5 (M+H)
361.1758, found 361.1750.
4.4.14. Ethyl 5-(cyclopropylamino)-2-phenyloxazole-
4-carboxylate (13n). H NMR (400 MHz, CDCl3) d 7.97–
1
7.99 (m, 2H), 7.37–7.45 (m, 3H), 6.50 (s, 1H), 4.37 (q,
J¼7.2 Hz, 2H), 2.81–2.87 (m, 1H), 1.41 (t, J¼3.6 Hz, 3H),
0.87–0.91 (m, 2H), 0.73–0.77 (m, 2H); 13C NMR
(100 MHz, CDCl3) d 164.3, 161.5, 150.8, 129.8, 128.9,
128.8, 127.1, 125.9, 60.5, 24.6, 14.9, 7.4. HRMS calcd for
C15H17N2O3 (M+H) 295.1053, found 295.1052.
4.4.9. Ethyl 5-(3,4-dihydroquinolin-1(2H )-yl)-2-phenyl-
oxazole-4-carboxylate (13i). H NMR (400 MHz, CDCl3)
4.4.15. (5-(4-Methylpiperazin-1-yl)-2-phenyloxazol-4-
yl)methanol (14). In a clean, dry 40 mL sample vial was
placed ethyl 5-(4-methylpiperazin-1-yl)-2-phenyloxazole-
4-carboxylate (0.089 g, 0.28 mmol) in dry dichloromethane
1
d 7.94–7.97 (m, 2H), 7.22–7.44 (m, 7H), 6.55 (d,
J¼8.4 Hz, 1H), 5.38 (q, J¼15.6, 7.6 Hz, 1H), 4.37 (q,
J¼14.4, 7.2 Hz, 2H), 3.07–3.14 (m, 1H), 2.91–2.99 (m,
1H), 2.68–2.77 (m, 1H), 2.02–2.11 (m, 1H), 1.39 (t,
J¼7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) d 164.3,
160.3, 150.4, 143.3, 142.4, 129.9, 128.9, 128.7, 127.2,
127.1, 125.9, 125.2, 124.2, 60.4, 59.0, 34.8, 30.4, 14.9.
ꢁ
under N2. The stirred solution was cooled to ꢃ78 C and
Dibal-H (0.84 mL, 0.84 mmol) was added via syringe. After
10 min, the reaction was complete by LC–MS and quenched
with H2O. After warming to rt the crude reaction mixture
was filtered through packed Celite and extracted with EtOAc