F. Zhang et al.
Bioorganic Chemistry 114 (2021) 105093
+
2
,5-Dimethoxy-N-(4-(4-(trifluoromethyl) phenyl) oxazol-2-yl)
for C17
H
17
N
3
O
2
(M + H) 296.1394; found 296.1384.
1
benzamide (Compound PA3): White powder, yield 38%. H NMR
300 MHz, DMSO‑d
) δ 11.26 (s, 1H), 8.63 (s, 1H), 7.97 (d, J = 8.1 Hz,
(3R,5R,7R)-N-(4-(4-Cyanophenyl) oxazol-2-yl) adamantane-1-
1
(
6
carboxamide (Compound PA15): Light yellow powder, yield 38%. H
2
H), 7.82 (d, J = 8.3 Hz, 2H), 7.22 (t, J = 1.7 Hz, 1H), 7.13 (d, J = 1.8
NMR (400 MHz, CDCl
3
) δ 8.25 (s, 1H), 7.83 (s, 1H), 7.79 (d, J = 8.2 Hz,
Hz, 2H), δ 3.85 (s, 3H), 3.76 (s, 3H). HRMS (ESI): calcd. for
2H), 7.69 (d, J = 8.4 Hz, 2H), 2.13 (s, 3H), 1.99 (d, J = 2.9 Hz, 5H),
+
C
19
H
15
F
N
3 2
O
4
(M + H) 393.1057; found 393.1050.
1.82–1.73 (m, 7H). HRMS (ESI): calcd. for C21
H
21
N
3
O
2
(M + H)
+
N-(4-(4-(Trifluoromethyl) phenyl) oxazol-2-yl) picolinamide
Compound PA4): White powder, yield 29%. 1H NMR (300 MHz,
CDCl
348.1707; found 348.1690.
(
N-(4-(4-Cyanophenyl) oxazol-2-yl) isobutyramide (Compound
1
3
) δ 10.80 (s, 1H), 8.66 (d, J = 4.7 Hz, 1H), 8.34 (d, J = 7.8 Hz, 1H),
3
PA16): Yellow powder, yield 35%. H NMR (300 MHz, CDCl ) δ 8.52 (s,
7
7
.99–7.86 (m, 1H), 7.87 (t, J = 4.1 Hz, 3H), 7.67 (d, J = 8.2 Hz, 2H),
1H), 7.81 (s, 1H), 7.78 (d, J = 8.5 Hz, 2H), 7.69 (d, J = 8.3 Hz, 2H), 2.83
.57 (dd, J = 7.6, 4.7 Hz, 1H); HRMS (ESI): calcd. for C16
H
10
F
3
N
3
O
2
(M
(s, 1H), 1.29 (d, J = 6.9 Hz, 6H). HRMS (ESI): calcd. for C14
13 3 2
H N O (M
+
+
+
H) 334.0798; found 334.079.
+ H) 256.1081; found 256.107.
5
-(Trifluoromethyl)-N-(4-(4-(trifluoromethyl) phenyl) oxazol-2-
N-(4-(4-Cyanophenyl) oxazol-2-yl) butyramide (Compound
1
1
yl) picolinamide (Compound PA5): Yellow powder, yield 72%.
H
3
PA17): Light yellow powder, yield 39%. H NMR (300 MHz, CDCl ) δ
NMR (300 MHz, DMSO‑d ) δ 11.98 (s, 1H), 9.16 (s, 1H), 8.72 (s, 1H),
6
8.47 (s, 1H), 7.79 (d, J = 8.3 Hz, 3H), 7.69 (d, J = 8.0 Hz, 2H), 2.61 (s,
8
2
.53 (d, J = 6.0 Hz, 1H), 8.34 (d, J = 8.2 Hz, 1H), 8.01 (d, J = 8.1 Hz,
2H), 1.79 (q, J = 7.4 Hz, 2H), 1.03 (t, J = 7.4 Hz, 3H). HRMS (ESI):
+
H), 7.84 (d, J = 8.2 Hz, 2H). HRMS (ESI): calcd. for C17
H
9
F
6
3
N O
2
(M +
calcd. for C14
H
13
3
N O
2
(M + H) 256.1081; found 256.1076.
+
H) 402.0672; found 402.0671.
N-(4-(4-(Trifluoromethyl) phenyl) oxazol-2-yl)-1-naphthamide
5.1.4. General procedure for the preparation of products PC1-PC6 (Take
PC4 as an example)
1
(
Compound PA6): White powder, yield 46%. H NMR (300 MHz,
DMSO‑d
6
) δ 12.04 (s, 1H), 8.70 (s, 1H), 8.32–8.28 (m, 1H), 8.18–8.14
The product P1 (1.0 mmol, 1.0 eq.) was dissolved in acetic acid, and
◦
(
m, 1H), 8.09–8.02 (m, 3H), 7.91–7.85 (m, 3H), 7.71–7.60 (m, 4H).
NBS (1.1 mmol, 1.1 eq.) was added at 0 C, they are stirred at room
+
HRMS (ESI): calcd. for C21
83.0996.
N-(4-(4-(Trifluoromethyl)
hexanecarboxamide (Compound PA7): White powder, yield 49%. H
NMR (300 MHz, CDCl
H
13
F
3
N
2
O
2
(M + H) 383.1002; found
temperature for 1 h. Observed that the solution changes color, used TLC
monitor the progress of the reaction. The reaction was quenched with an
3
phenyl)
oxazol-2-yl)
cyclo-
appropriate amount of saturated NaHCO
3
solution, and extracted 3
SO . The
1
times with EA. The organic layer was dried with anhydrous Na
2
4
3
) δ 7.79 (d, J = 7.4 Hz, 3H), 7.66 (d, J = 8.2 Hz,
organic layer was evaporated under reduced pressure. The residue was
2
H), 2.66–2.39 (m, 1H), 2.00–1.52 (m, 10H). HRMS (ESI): calcd. for
purified by chromatography on silica (PE: EA = 5: 1) to afford PC1-PC6.
+
C
17
H
17
F
3
N
2
O
2
(M + H) 339.1315; found 339.1306.
3R,5R,7R)-N-(4-(4-(Trifluoromethyl) phenyl) oxazol-2-yl) ada-
mantane-1-carboxamide (Compound PA8): Light yellow powder,
N-(5-Bromo-4-(4-(trifluoromethyl)
phenyl)
oxazol-2-yl)-5-
(
(trifluoromethyl) picolinamide (Compound PC1): Light yellow
1
powder, yield 46%. H NMR (300 MHz, DMSO‑d ) δ 12.16 (s, 1H), 9.15
6
1
yield 26%. H NMR (400 MHz, DMSO‑d
6
) δ 10.75 (s, 1H), 8.59 (s, 1H),
(s, 1H), 8.53 (dd, J = 8.2, 2.3 Hz, 1H), 8.33 (d, J = 8.2 Hz, 1H), 8.13 (d, J
7
1
.96 (d, J = 8.1 Hz, 2H), 7.80 (d, J = 8.2 Hz, 2H), 1.93–1.91 (m, 4H),
= 8.1 Hz, 2H), 7.91 (d, J = 8.3 Hz, 2H). HRMS (ESI): calcd. for
+
.79–1.78 (m, 3H), 1.70–1.64 (m, 8H). HRMS (ESI): calcd. for
C
17
H
8
BrF
6
N
3
O
2
(M + H) 479.9777; found 479.9780.
+
C
21
H
21
F
3
N
2
O
2
(M + H) 391.1628; found 391.1622.
N-(5-Chloro-4-(4-(trifluoromethyl)
phenyl)
oxazol-2-yl)-5-
N-(4-(4-(Trifluoromethyl) phenyl) oxazol-2-yl) isobutyramide
Compound PA9): White powder, yield 51%. 1H NMR (400 MHz,
CDCl
(trifluoromethyl) picolinamide (Compound PC2): Yellow powder,
1
(
6
yield 35%. H NMR (400 MHz, DMSO‑d ) δ 12.19 (s, 1H), 9.15 (s, 1H),
3
) δ 7.79 (d, J = 4.0 Hz, 2H), 7.78 (s, 1H), 7.65 (d, J = 7.8 Hz, 2H),
8.54 (d, J = 8.3 Hz, 1H), 8.34 (d, J = 8.2 Hz, 1H), δ 8.09 (d, J = 8.0 Hz,
2
.81 (s, 1H), 1.28 (d, J = 6.9 Hz, 6H). HRMS (ESI): calcd. for
2H), 7.90 (d, J = 8.2 Hz, 2H). HRMS (ESI): calcd. for C17
H
8
ClF
6 3 2
N O (M
+
+
C
14
H
13
F
3
N
2
O
2
(M + H) 299.1002; found 299.0993.
+ H) 436.0282; found 436.0274.
N-(4-(4-(Trifluoromethyl) phenyl) oxazol-2-yl) butyramide
Compound PA10): White powder, yield 51%. 1H NMR (400 MHz,
DMSO‑d
) δ 11.36 (s, 1H), 8.55 (s, 1H), 7.87 (dd, J = 57.4, 8.2 Hz, 4H),
.39 (t, J = 7.4 Hz, 2H), 1.61 (h, J = 7.3 Hz, 2H), 0.92 (t, J = 7.4 Hz, 3H).
N-(5-Iodo-4-(4-(trifluoromethyl)
phenyl)
oxazol-2-yl)-5-
(
(trifluoromethyl) picolinamide (Compound PC3): White powder,
1
6
6
yield 75%. H NMR (400 MHz, DMSO‑d ) δ 12.08 (s, 1H), 9.15 (s, 1H),
2
8.53 (dd, J = 8.3, 2.3 Hz, 1H), 8.33 (d, J = 8.2 Hz, 1H), 8.17 (d, J = 8.1
+
HRMS (ESI): calcd. for C14
99.0990.
N-(4-(4-Cyanophenyl) oxazol-2-yl) picolinamide (Compound
H
13
F
3
2
N O
2
(M + H)
299.1002; found
Hz, 2H), 7.90 (d, J = 8.3 Hz, 2H). HRMS (ESI): calcd. for C17
8 6 3 2
H F IN O
+
2
(M + H) 527.9638; found 527.9628.
N-(5-Bromo-4-(4-(trifluoromethyl) phenyl) oxazol-2-yl)-2,6-
1
PA11): White powder, yield 22%. H NMR (400 MHz, DMSO‑d
6
) δ 11.69
dimethoxybenzamide (Compound PC4): White powder, yield 40%.
1
(
s, 1H), 8.77 (d, J = 4.4 Hz, 1H), 8.72 (s, 1H), 8.17–8.08 (m, 2H),
H NMR (400 MHz, DMSO‑d
6
) δ 11.89 (s, 1H), 8.10 (d, J = 7.3 Hz, 2H),
7
.98–7.92 (m, 4H), 7.76–7.73 (m, 1H); HRMS (ESI): calcd. for
7.89 (d, J = 8.0 Hz, 2H), 7.39 (t, J = 8.4 Hz, 1H), 6.75 (d, J = 8.4 Hz,
+
13
C
16
H
10
N
4
O
2
(M + H) 291.0877; found 291.0868.
6
2H), 3.78 (s, 6H). C NMR (126 MHz, DMSO‑d ) δ 163.00, 157.25,
N-(4-(4-Cyanophenyl) oxazol-2-yl)-5-(trifluoromethyl) picoli-
154.17, 134.93, 134.10, 131.73, 128.93 (q, J = 31.9 Hz), 126.91,
1
namide (Compound PA12): Light yellow powder, yield 51%. H NMR
300 MHz, DMSO‑d ) δ 11.97 (s, 1H), 9.15 (s, 1H), 8.74 (s, 1H), 8.53 (d,
126.22 (q, J = 4.0 Hz), 124.59 (q, J = 273.4 Hz), 115.13, 114.08,
(
6
104.71, 56.36. HRMS (ESI): calcd. for C19
3
H14BrF N
2
O
4
(M + H)
+
J = 8.4 Hz, 1H), 8.33 (d, J = 8.3 Hz, 1H), 7.99–7.92 (m, 4H); HRMS
471.0162; found 471.0150.
+
(
ESI): calcd. for C17
9
H F3N
4
O
2
(M + H) 359.0750; found 359.0742.
N-(5-Chloro-4-(4-(trifluoromethyl) phenyl) oxazol-2-yl)-2,6-
N-(4-(4-Cyanophenyl) oxazol-2-yl)-1-naphthamide (Compound
dimethoxybenzamide (Compound PC5): White powder, yield 69%.
1
1
PA13): White powder, yield 26%. H NMR (400 MHz, DMSO‑d
6
) δ 12.04
H NMR (300 MHz, DMSO‑d
6
) δ 11.90 (s, 1H), 8.05 (d, J = 8.0 Hz, 2H),
(
s, 1H), 8.71 (s, 1H), 8.26 (d, J = 7.3 Hz,1H), 8.14 (d, J = 8.3 Hz, 1H),
7.88 (d, J = 8.0 Hz, 2H), 7.39 (t, J = 8.4 Hz, 1H), 6.75 (d, J = 8.5 Hz,
8
.05 (dd, J = 6.9, 2.4 Hz, 1H), 7.95 (q, J = 8.4 Hz, 4H), 7.86 (d, J = 7.0
2H), 3.78 (s, 6H). 13C NMR (126 MHz, DMSO‑d
6
) δ 163.06, 157.25,
Hz, 1H), 7.70–7.57 (m, 3H). HRMS (ESI): calcd. for C21
H
13
N
3
O
2
(M + H)
151.97, 133.69, 131.75, 131.05, 128.9(q, J = 31.5 Hz), 127.10, 126.82,
+
3
40.1081; found 340.1072.
126.27 (q, J = 3.78 Hz), 124.57(q, J = 272.2 Hz), 115.08, 104.71, 56.36.
+
N-(4-(4-Cyanophenyl) oxazol-2-yl) cyclohexanecarboxamide
HRMS (ESI): calcd. for C19
427.0657.
H14ClF
3
N
2
O
4
(M + H) 427.0667; found
1
(
Compound PA14): White powder, yield 55%. H NMR (300 MHz,
CDCl
) δ 8.39 (s, 1H), 7.81 (s, 1H), 7.78 (d, J = 8.1 Hz, 2H), 7.69 (d, J =
.1 Hz, 2H), 2.60–2.41 (m, 1H), 2.00–1.37 (m, 10H). HRMS (ESI): calcd.
3
N-(5-Iodo-4-(4-(trifluoromethyl)
phenyl)
oxazol-2-yl)-2,6-
8
dimethoxybenzamide (Compound PC6): White powder, yield 72%.
1
0