Journal of Medicinal Chemistry
Article
NMR (CDCl3, 100 MHz) δ 18.3, 76.6, 111.0, 111.8, 113.0, 119.0, 120.9,
122.7, 124.1, 127.8, 134.1, 134.3, 134.5, 142.2, 147.8, 150.7, 153.5, 161.5,
168.9; ESI-HRMS for C21H16N3O3Cl2 (M + H)+ calcd 428.0569, found
428.0569.
161.8, 168.9; ESI-HRMS for C22H16N3O3ClF3 (M + H)+ calcd
462.0832, found 462.0834; chiral purity, 99.4% ee (tR = 11.83).
(S)-2-(2-Chloro-3-nitrophenoxy)-N-(2-(pyridine-4-yl)benzo-
[d]oxazol-5-yl)propionamide (57). Yield, 77%; cream colored solid;
1H NMR (CDCl3, 400 MHz) δ 1.80 (d, J = 6.8 Hz, 3H), 4.97 (q, J = 6.8
Hz, 1H), 7.24 (d, J = 8.4 Hz, 1H), 7.44 (t, J = 8.4 Hz, 1H), 7.53−7.62 (m,
3H), 8.07−8.09 (m, 2H), 8.20 (s, 1H), 8.68 (s, 1H), 8.82−8.84 (m, 2H);
13C NMR (CDCl3, 100 MHz) δ 18.5, 76.9, 111.3, 112.2, 117.2, 118.0,
118.7, 119.3, 121.2, 128.4, 134.2, 134.4, 142.4, 148.1, 149.9, 150.9, 153.7,
161.9, 168.6; ESI-HRMS for C21H16N4O5Cl (M + H)+ calcd 439.0809,
found 439.0805; chiral purity, >99% ee (tR = 35.93).
2-(2,6-Dichlorophenoxy)-N-(2-(pyridine-4-yl)benzo[d]-
1
oxazol-5-yl)propionamide (47). Yield, 67%; white solid; H NMR
(CDCl3, 400 MHz) δ 1.61 (d, J = 6.8 Hz, 3H), 5.11 (q, J = 6.8 Hz, 1H),
7.09 (t, J = 7.6 Hz, 1H), 7.37 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 8.8 Hz, 1H),
7.18 (dd, J1 = 8.8 Hz, J2 = 1.6 Hz, 1H), 8.08 (d, J = 5.2 Hz, 2H), 8.20 (s,
1H), 8.82 (d, J = 5.2 Hz, 2H), 8.99 (s, 1H); 13C NMR (CDCl3, 100
MHz) δ 18.2, 79.5, 111.1, 112.1, 119.4, 121.2, 126.1, 129.5, 129.6, 134.3,
135.0, 142.4, 148.0, 148.7, 150.9, 169.5, 195.9; ESI-HRMS for
C21H16N3O3Cl2 (M + H)+ calcd 428.0569, found 428.0567.
(S)-2-(2,3-Dimethoxyphenoxy)-N-(2-(pyridine-4-yl)benzo[d]-
1
oxazol-5-yl)propionamide (58). Yield, 79%; white solid; H NMR
2-(Naphthalene-1-yloxy)-N-(2-(pyridine-4-yl)benzo[d]-
(CDCl3, 400 MHz) δ 1.78 (d, J = 6.8 Hz, 3H), 3.89 (s, 3H), 4.01 (s, 3H),
4.78 (q, J = 6.8 Hz, 1H), 6.67−6.71 (m, 2H), 7.04 (t, J = 5.6 Hz, 1H),
7.55 (d, J = 8.8 Hz, 1H), 7.68 (dd, J1 = 9.2 Hz, J2 = 2.4 Hz, 1H), 8.07 (dd,
J1 = 4.4 Hz, J2 = 1.6 Hz, 2H), 8.20 (d, J = 2 Hz, 1H), 8.82 (dd, J1 = 4.4 Hz,
J2 = 1.2 Hz, 2H), 9.58 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ 20.5,
57.0, 62.5, 80.3, 108.3, 111.4, 111.8, 112.7, 120.1, 122.0, 125.7, 135.3,
136.4, 140.4, 143.1, 148.6, 151.7, 152.8, 154.9, 162.4, 171.4; ESI-HRMS
for C23H22N3O5 (M + H)+ calcd 420.1559, found 420.1557; chiral
purity, >99% ee (tR = 17.41).
1
oxazol-5-yl)propionamide (48). Yield, 73%; white solid; H NMR
(CDCl3, 400 MHz) δ 1.84 (d, J = 6.4 Hz, 3H), 5.04 (q, J = 6.8 Hz, 1H),
6.92 (d, J = 7.6 Hz, 1H), 7.39 (t, J = 8 Hz, 1H), 7.61−7.48 (m, 5H),
7.89−7.86 (m,1H), 8.05−8.08 (m, 3H), 8.33−8.36 (m, 1H), 8.41 (s,
1H), 8.80 (s, 2H); 13C NMR (CDCl3, 100 MHz) δ 19.1, 76.2, 107.3,
111.1, 112.4, 119.6, 121.21, 121.25, 121.5, 122.4, 125.8, 126.0, 126.1,
127.0, 128.1, 134.2, 134.6, 134.9, 142.4, 148.0, 150.9, 152.6, 170.6; ESI-
HRMS for C25H20N3O3 (M + H)+ calcd 410.1505, found 410.1508.
2-(4-Chloronaphthalen-1-yloxy)-N-(2-(pyridin-4-yl)benzo[d]-
2-(2,4-Dichlorophenoxy)-N-(2-(phenylbenzo[d]oxazol-5-yl)-
1
1
oxazol-5-yl)propionamide (49). Yield, 68%; white solid. H NMR
propionamide (59). Yield, 73%; white solid; H NMR (CDCl3, 400
(CDCl3, 400 MHz) δ 1.83 (d, J = 6.8 Hz, 3H), 5.0 (q, J = 6.8 Hz, 1H),
6.84 (d, J = 8.4 Hz, 1H), 7.46−7.50 (m, 2H), 7.54 (d, J = 8.8 Hz, 1H),
7.63−7.71 (m, 2H), 8.04−8.07 (m, 3H), 8.27 (d, J = 8 Hz, 1H), 8.36 (d,
J = 8 Hz, 2H), 8.81 (d, J = 4 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ
19.0, 76.5, 107.3, 111.1, 112.5, 119.6, 121.1, 122.0, 124.9, 125.5, 125.9,
126.9, 128.1, 131.8, 134.2, 134.4, 134.4, 134.7, 142.4, 148.1, 150.9, 151.7,
161.8, 170.3; ESI-HRMS for C25H19N3O3Cl (M + H)+ calcd 444.1115,
found 444.1119.
MHz) δ 1.74 (d, J = 6.8 Hz, 3H), 4.84 (q, J = 6.8 Hz, 1H), 6.94 (d, J = 8.8
Hz, 1H), 7.23 (dd, J1 = 8.8 Hz, J2 = 2.4 Hz, 1H), 7.44 (d, J = 2.4 Hz, 1H),
7.54−7.51 (m,4H), 7.56 (d, J = 2 Hz, 1H), 7.59 (d, J = 2 Hz, 1H), 8.05
(d, J = 1.6 Hz, 1H), 8.24 (dd, J = 8 Hz, 2H), 8.75 (s, 1H); 13C NMR
(CDCl3, 100 MHz) δ 18.6, 76.9, 110.8, 111.6, 116.4, 118.0, 124.7, 127.1,
127.8, 128.0, 128.4, 129.1, 130.6, 131.9, 134.2, 142.8, 148.0, 151.3, 164.2,
169.1; ESI-HRMS for C22H17N2O3Cl2 (M + H)+ calcd 427.0616 found
427.0619.
3-Methyl-2-(naphthalene-1-yloxy)-N-(2-(pyridine-4-yl)-
benzo[d]oxazol-5-yl)butanamide (52). Yield, 67%; white solid; 1H
NMR (CDCl3, 400 MHz) δ 1.18 (d, J = 6.8 Hz, 3H), 1.25 (d, J = 6.8 Hz,
3H), 2.51−2.59 (m, 1H), 4.69 (d, J = 4 Hz, 1H), 6.84 (d, J = 7.6 Hz, 1H),
7.31 (t, J = 8 Hz, 1H), 7.37−7.47 (m, 3H), 7.51−7.54 (m, 2H), 7.80 (t,
J = 6.4 Hz, 1H), 7.95−7.97 (m, 3H), 8.34 (d, J = 5.6 Hz, 2H), 8.72 (d, J =
5.2 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ 17.5, 19.6, 32.5, 84.5,
106.7, 111.0, 112.7, 119.9, 121.1, 121.5, 122.1, 125.7, 126.0, 127.0, 128.1,
134.2, 134.4, 134.8, 142.2, 148.0, 150.7, 153.5, 161.6, 169.8; ESI-HRMS
for C27H24N3O3 (M + H)+ calcd 438.1818, found 438.1822.
(S)-2-(2,3-Dichlorophenoxy)-N-(2-(thiazol-5-yl)benzo[d]-
1
oxazol-5-yl)propionamide (62). Yield, 76%; white solid; H NMR
(CDCl3, 400 MHz) δ 1.76 (d, J = 6.8 Hz, 3H), 4.89 (q, J = 6.8 Hz, 1H),
6.92 (dd, J1 = 7.2 Hz, J2 = 2.4 Hz, 1H), 7.17−7.22 (m, 2H), 7.55 (q, J =
8.8 Hz, 2H), 8.09 (s, 1H), 8.64 (s, 1H), 8.81 (s, 1H); 13C NMR (CDCl3,
100 MHz) δ 18.6, 76.9, 110.9, 111.6, 113.2, 118.6, 120.5, 122.9, 124.3,
125.7, 128.1, 134.7, 142.4, 145.7, 147.6, 153.7, 156.4, 158.0, 169.1; ESI-
HRMS for C19H14N3O3SCl2 (M + H)+ calcd 434.0133, found 434.0136;
chiral purity, 99.1% ee (tR = 15.5).
(S)-2-(Naphthalene-1-yloxy)-N-(2-(thiazol-5-yl)benzo[d]-
1
oxazol-5-yl)propionamide (63). Yield, 78%; white solid; H NMR
(R)-2-(Naphthalene-1-yloxy))-N-(2-(pyridine-4-yl)benzo[d]-
1
oxazol-5-yl)propionamide (53). Yield, 76%; white solid; H NMR
(CDCl3, 400 MHz) δ 1.81 (d, J = 6.8 Hz, 3H), 5.01 (q, J = 6.4 Hz, 1H),
6.89 (d, J = 7.6 Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H), 7.45−7.54 (m, 5H),
7.82 (t, J = 4.8 Hz, 1H), 7.96 (s, 1H), 8.29 (d, J = 5.2 Hz, 1H), 8.55 (d, J =
21.6 Hz, 2H), 8.91 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ 19.1, 76.2,
107.3, 110.7, 112.0, 119.0, 121.5, 122.3, 125.6, 125.8, 126.0, 126.1, 127.0,
128.0, 134.6, 134.8, 142.2, 145.6, 147.6, 152.6, 156.4, 157.8, 170.6; ESI-
HRMS for C23H18N3O3S (M + H)+ calcd 416.1069, found 416.1075;
chiral purity, 98.7% ee (tR = 12.53).
(CDCl3, 400 MHz) δ 1.83 (d, J = 6.8 Hz, 3H), 5.03 (q, J = 6.8 Hz, 1H),
6.91 (d, J = 7.6 Hz, 1H), 7.38 (t, J = 8 Hz, 1H), 7.50−7.58 (m, 5H),
7.85−7.87 (m, 1H), 8.03−8.07 (m, 3H), 8.34 (t, J = 2.8 Hz, 1H), 8.47 (s,
1H), 8.80 (bs, 2H); 13C NMR (CDCl3, 100 MHz) δ 19.1, 67.3, 76.2,
107.3, 111.1, 112.4, 119.6, 121.2, 121.5, 122.4, 125.8, 126.0, 126.1, 127.0,
128.1, 134.3, 134.6, 134.9, 142.3, 148.0, 150.9, 152.6, 161.7, 170.6; ESI-
HRMS for C25H20N3O3 (M + H)+ calcd 410.1505, found 410.1508;
chiral purity, 98.1% ee (tR = 22.87).
2-(4-Chloronaphthalen-1-yloxy)-N-(2-(thiazol-5-yl)benzo[d]-
1
oxazol-5-yl)propionamide (64). Yield, 64%; white solid; H NMR
(S)-2-(Naphthalene-1-yloxy))-N-(2-(pyridine-4-yl)benzo[d]-
1
oxazol-5-yl)propionamide (54). Yield, 71%; white solid; H NMR
(CDCl3, 400 MHz) δ 1.82 (d, J = 6.8 Hz, 3H), 4.99 (q, J = 6.8 Hz, 1H),
6.83 (d, J = 8.4 Hz, 1H), 7.44−7.50 (m, 3H), 7.62−7.71 (m, 2H), 7.98
(d, J = 2 Hz, 1H), 8.25−8.37 (m, 3H), 8.62 (s, 1H), 8.96 (s, 1H); 13C
NMR (CDCl3, 100 MHz) δ 19.1, 76.6, 107.4, 110.9, 112.1, 119.0, 122.0,
125.0, 125.6, 126.0, 126.9, 127.0, 128.2, 131.8, 134.5, 142.4, 145.8, 147.8,
151.7, 156.5, 161.8, 166.4, 170.3; ESI-HRMS for C23H17N3O3SCl
(M + H)+ calcd 450.0679, found 450.0680.
(CDCl3, 400 MHz) δ 1.78 (d, J = 6.8 Hz, 3H), 4.96 (q, J = 6.8 Hz, 1H),
6.85 (d, J = 7.6 Hz, 1H), 7.30 (t, J = 8 Hz, 1H), 7.50−7.42 (m, 5H),
7.77−7.79 (m, 1H), 7.92 (dd, J1 = 4.4 Hz, J2 = 1.6 Hz, 2H), 8.02 (s, 1H),
8.26−8.23 (m, 1H), 8.60 (s, 1H), 8.70 (d, J = 4.4 Hz, 2H); 13C NMR
(CDCl3, 100 MHz) δ 19.1, 76.2, 107.2, 111.0, 112.5, 119.7, 121.1, 121.5,
122.3, 125.0, 125.8, 126.0, 126.9, 128.0, 134.1, 134.7, 134.8, 142.2, 147.9,
150.8, 152.7, 161.6, 170.7; ESI-HRMS for C25H20N3O3 (M + H)+ calcd
410.1505, found 410.1507; chiral purity, 98.9% ee (tR = 12.08).
(S)-2-(2,3-Dichlorophenoxy)-N-(2-(thiazol-2-yl)benzo[d]-
1
oxazol-5-yl)propionamide (65). Yield, 69%; white solid; H NMR
(CDCl3, 400 MHz) δ 1.72 (d, J = 6.8 Hz, 3H), 4.85 (q, J = 6.8 Hz, 1H),
6.89 (dd, J1 = 8 Hz, J2 = 2 Hz, 1H), 7.12−7.18 (m, 2H), 7.55 (bs, 2H),
7.59 (d, J = 2.8 Hz, 1H), 8.03 (d, J = 3.2 Hz, 1H), 8.14 (d, J = 1.2 Hz,
1H); 13C NMR (CDCl3, 100 MHz) δ 18.6, 77.0, 111.5, 112.0, 113.2,
119.5, 122.9, 123.5, 124.3, 128.0, 134.5, 134.9, 142.0, 145.3, 147.8, 153.7,
154.7, 158.0, 169.2; ESI-HRMS for C19H14N3O3SCl2 (M + H)+ calcd
434.0133, found 434.0132; chiral purity, >99% ee (tR = 12.88).
(S)-2-(2-Chloro-3-(trifluoromethyl)phenoxy)-N-(2-(pyridine-
4-yl)benzo[d]oxazol-5-yl)propionamide (56). Yield, 70%; cream
colored solid; 1H NMR (CDCl3, 400 MHz) δ 1.78 (d, J = 6.8 Hz, 3H),
4.94 (q, J = 6.4 Hz, 1H), 7.21 (d, J = 7.6 Hz, 1H), 7.37−7.44 (m, 2H),
7.59 (s, 2H), 8.07 (d, J = 5.2 Hz 2H), 8.19 (s, 1H), 8.82 (d, J = 5.6 Hz,
3H); 13C NMR (CDCl3, 100 MHz) δ 18.5, 76.9, 111.2, 112.1, 118.4,
119.2, 121.1, 122.3, 124.0, 130.4, 134.2, 134.6, 142.4, 148.0, 150.9, 153.5,
K
dx.doi.org/10.1021/jm400241j | J. Med. Chem. XXXX, XXX, XXX−XXX