Journal of Agricultural and Food Chemistry
Article
1
+
62.0, 166.8. HRMS m/z (ESI): Calculated for C H BrF N O ([M
H] ): 464.0140, found 464.0138.
165.7, 168.9. HRMS m/z (ESI): Calculated for C H BrF N O ([M
15 9 5 5
+ H] ): 449.9983, found 449.9993.
1
6
11
5
5
+
+
5
-Chloro-N-(3-fluoro-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-
5-Chloro-6-(difluoromethyl)-N-(4-(5-(trifluoromethyl)-1,2,4-oxa-
yl)benzyl)-6-(1-fluoroethyl)pyrimidin-4-amine (U10). White solid,
diazol-3-yl)benzyl)pyrimidin-4-amine (U16). White solid, m.p. 87−
1
1
m.p. 83−84 °C, yield 51.5%; H NMR (CDCl , 600 MHz) δ: 1.68
dd, J = 24.0 Hz, 6.6 Hz, 3H, -CH ), 4.84 (t, J = 6.0 Hz, 2H, -CH ),
.86−5.97 (m, 1H, -CH), 6.02 (t, J = 6.0 Hz, 1H, -NH), 7.24 (d, J =
0.8 Hz, 1H, Ar-H), 7.28 (d, J = 8.4 Hz, 1H, Ar-H), 8.06 (t, J = 7.2
Hz, 1H, Ar-H), 8.54 (s, 1H, Pyrimidine-H). C NMR (CDCl , 150
MHz) δ: 19.2 (d, JC‑F = 24.2 Hz, -CHFCH ), 44.2, 86.2, 87.3, 111.5,
88 °C, yield 51.3%; H NMR (CDCl , 600 MHz) δ: 4.86 (d, J = 6.0
3
3
(
5
1
Hz, 2H, -CH ), 6.05−6.10 (m, 1H, -NH), 6.74 (t, J = 53.4 Hz, 1H,
3
2
2
-CHF ), 7.49 (d, J = 8.4 Hz, 1H, Ar-H), 8.11 (d, J = 7.8 Hz, 2H, Ar-
2
1
3
H), 8.59 (s, 1H, Pyrimidine-H). C NMR (CDCl , 150 MHz) δ:
3
1
3
44.9, 109.9, 111.5 (t, JC‑F = 240.0 Hz, -CHF ), 113.1, 116.5 (q, J
=
3
2
C‑F
2
272.1 Hz, -CF ), 124.4, 128.2 (d, J = 7.8 Hz), 142.0, 152.6, 156.1,
3
3 C‑F
1
12.5, 115.6 (d, JC‑F = 21.3 Hz, Ar-F), 116.5 (q, J = 272.1 Hz,
158.4, 166.0, 168.8. HRMS m/z (ESI): Calculated for C H ClF N O
15 9 5 5
([M + H] ): 406.0489, found 406.0492.
C‑F
2
+
-
CF ), 123.5, 131.2 (d, J = 31.8 Hz), 145.3, 155.9, 157.9, 160.1,
3
C‑F
1
+
61.8, 165.8. HRMS m/z (ESI): Calculated for C H ClF N O ([M
H] ): 420.0645, found 420.0640.
6-(Difluoromethyl)-N-(4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-
1
6
11
5
5
+
yl)benzyl)pyrimidin-4-amine (U17). White solid, m.p. 120−121 °C,
1
5
-Bromo-6-(1-fluoroethyl)-N-((5-(5-(trifluoromethyl)-1,2,4-oxa-
yield 58.4%; H NMR (CDCl
3
, 600 MHz) δ: 4.73 (s, 2H, -CH
2
),
diazol-3-yl)pyridin-2-yl)methyl)pyrimidin-4-amine (U11). White
solid, m.p. 132−133 °C, yield 52.3%; H NMR (CDCl , 600 MHz)
δ: 1.66 (dd, J = 24.0 Hz, 6.0 Hz, 3H, -CH ), 4.89 (t, J = 4.8 Hz, 2H,
6.72−5.77 (m, 1H, -NH), 6.41 (t, J = 53.4 Hz, 1H, -CHF ), 6.66 (s,
2
1
1H, Pyrimidine-H), 7.48 (d, 2H, J = 8.4 Hz, Ar-H), 8.11 (d, 2H, J =
3
1
3
8.4 Hz, Ar-H), 8.61 (s, 1H, Pyrimidine-H). C NMR (CDCl , 150
3
3
-
CH ), 5.85−5.96 (m, 1H, -CH), 7.03 (s, 1H, -NH), 7.48 (d, J = 8.4
MHz) δ: 44.9, 110.8, 112.4 (t, JC‑F = 240.0 Hz, -CHF ), 114.0, 116.5
2
2
2
Hz, 1H, Py-H), 8.37 (dd, J = 8.4 Hz, 2.4 Hz, 1H, Py-H), 8.55 (s, 1H,
Py-H), 9.32 (d, J = 1.8 Hz, 1H, Pyrimidine-H). C NMR (CDCl3,
1
1
3
Calculated for C H BrF N O ([M + H] ): 447.0187, found
4
(q, JC‑F = 272.1 Hz, -CF ), 124.4, 128.2 (d, J = 7.8 Hz), 142.0,
3
C‑F
1
3
155.5, 157.6, 158.8, 166.0, 168.8. HRMS m/z (ESI): Calculated for
+
50 MHz) δ: 19.4 (d, JC‑F = 24.3 Hz, -CHFCH ), 45.2, 87.8, 88.9,
C H F N O ([M + H] ): 372.0878, found 372.0878.
3
15 10
5
5
2
02.7, 116.5 (q, JC‑F = 272.1 Hz, -CF ), 120.3, 122.1, 135.7 (d, J
=
5-Bromo-6-(difluoromethyl)-N-(2-fluoro-4-(5-(trifluoromethyl)-
3
C‑F
1.8 Hz), 148.3, 156.7, 158.4, 159.9, 161.7, 167.1. HRMS m/z (ESI):
1,2,4-oxadiazol-3-yl)benzyl)pyrimidin-4-amine (U18). White solid,
+
1
m.p. 93−94 °C, yield 53.2%; H NMR (CDCl
, 600 MHz) δ: 4.89 (d,
1
5
11
4
6
3
47.0186.
J = 6.0 Hz, 2H, -CH
1H, -CHF ), 7.55 (t, J = 7.8 Hz, 1H, Ar-H), 7.85 (d, J = 9.6 Hz, 1H,
Ar-H), 7.89 (d, J = 8.4 Hz, 1H, Ar-H), 8.59 (s, 1H, Pyrimidine-H).
2
), 6.16−6.26 (m, 1H, -NH), 6.72 (t, J = 53.4 Hz,
5
-Chloro-6-(1-fluoroethyl)-N-((5-(5-(trifluoromethyl)-1,2,4-oxa-
2
diazol-3-yl)pyridin-2-yl)methyl)pyrimidin-4-amine (U12). White
solid, m.p. 125−126 °C, yield 53.3%; H NMR (CDCl , 600 MHz)
δ: 1.66 (dd, J = 24.0 Hz, 6.0 Hz, 3H, -CH ), 4.90 (t, J = 4.8 Hz, 2H,
1
13
C NMR (CDCl , 150 MHz) δ: 39.4, 102.8, 110.7, 112.3 (t, J
=
3
3
C‑F
3
240.0 Hz, -CHF ), 114.8 (d, J = 24.1 Hz, Ar-F), 116.5 (q, J
272.1 Hz, -CF ), 123.7, 126.3, 129.0, 130.8 (d, J = 7.8 Hz), 142.0,
3 C‑F
2 C‑F
C‑F
=
2
-
CH ), 5.86−5.97 (m, 1H, -CH), 6.95 (s, 1H, -NH), 7.48 (d, J = 8.4
2
Hz, 1H, Py-H), 8.37 (dd, J = 8.4 Hz, 2.4 Hz, 1H, Py-H), 8.55 (s, 1H,
155.5, 157.6, 161.9, 168.0. HRMS m/z (ESI): Calculated for
1
3
+
Py-H), 9.31 (d, J = 1.8 Hz, 1H, Pyrimidine-H). C NMR (CDCl3,
C H BrF N O ([M + H] ): 467.9889, found 467.9887.
15
8
6
5
1
1
3
50 MHz) δ: 19.1 (d, JC‑F = 24.3 Hz, -CHFCH ), 45.9, 86.1, 87.3,
5-Chloro-6-(difluoromethyl)-N-(2-fluoro-4-(5-(trifluoromethyl)-
3
2
11.7, 116.7 (q, JC‑F = 272.1 Hz, -CF ), 120.3, 122.1, 135.7 (d, J
=
1,2,4-oxadiazol-3-yl)benzyl)pyrimidin-4-amine (U19). White solid,
3
C‑F
1
1.8 Hz), 148.3, 155.9, 157.8, 159.9, 166.1, 167.1. HRMS m/z (ESI):
m.p. 85−86 °C, yield 52.3%; H NMR (CDCl , 600 MHz) δ: 4.90 (d,
3
+
Calculated for C H ClF N O ([M + H] ): 403.0692, found
4
J = 6.0 Hz, 2H, -CH ), 6.10−6.16 (m, 1H, -NH), 6.73 (t, J = 53.4 Hz,
1H, -CHF ), 7.55 (t, J = 7.8 Hz, 1H, Ar-H), 7.85 (dd, J = 10.2 Hz, 1.2
1
5
11
4
6
2
03.0692.
-Chloro-N-(2,3-difluoro-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-
-yl)benzyl)-6-(1-fluoroethyl)pyrimidin-4-amine (U13). White solid,
2
5
Hz, 1H, Ar-H), 7.90 (dd, J = 8.4 Hz, 1.8 Hz, 1H, Ar-H), 8.58 (s, 1H,
1
3
3
Pyrimidine-H). C NMR (CDCl , 150 MHz) δ: 39.2, 102.8, 109.8,
3
1
m.p. 120−121 °C, yield 57.0%; H NMR (CDCl , 600 MHz) δ: 1.67
(
111.4, 114.8 (t, JC‑F = 240.0 Hz, -CHF ), 115.0 (d, J = 24.1 Hz,
3
2
C‑F
2
dd, J = 24.0 Hz, 6.6 Hz, 3H, -CH ), 4.90 (d, J = 6.6 Hz, 2H, -CH ),
-CHF ), 116.5 (q, J = 272.1 Hz, -CF ), 126.3, 129.1, 130.9 (d, J
3
2
2 C‑F 3 C‑F
5
.84−5.96 (m, 1H, -CH), 6.00−6.04 (m, 1H, -NH), 7.32 (t, J = 7.2
= 7.8 Hz), 152.7, 156.0, 158.4, 160.3, 161.9, 168.0. HRMS m/z (ESI):
+
Hz, 1H, Ar-H), 7.82 (t, J = 6.6 Hz, 1H, Ar-H), 8.56 (s, 1H,
Calculated for C H ClF N O ([M + H] ): 424.0394, found
1
5
8
6
5
Pyrimidine-H). 13C NMR (CDCl , 150 MHz) δ: 19.2 (d, J = 24.2
3
C‑F
424.0387.
Hz, -CHFCH ), 38.8, 86.2, 87.3, 111.6, 114.5 (d, J = 21.3 Hz, Ar-
F), 116.5 (q, J = 272.1 Hz, -CF ), 124.9 (d, J = 4.05 Hz, Ar-F),
6-(Difluoromethyl)-N-(2-fluoro-4-(5-(trifluoromethyl)-1,2,4-oxa-
3
C‑F
diazol-3-yl)benzyl)pyrimidin-4-amine (U20). White solid, m.p. 115−
C‑F
3
C‑F
2
1
1
1
31.8 (d, J = 31.8 Hz), 148.2, 150.3, 155.9, 157.8, 160.2, 165.6,
116 °C, yield 53.5%; H NMR (CDCl , 600 MHz) δ: 4.78 (s, 2H,
C‑F
3
65.9. HRMS m/z (ESI): Calculated for C H ClF N O ([M +
-CH ), 5.60−5.75 (m, 1H, -NH), 6.41 (t, J = 53.4 Hz, 1H, -CHF ),
1
6
10
6
5
2
2
+
H] ): 438.0551, found 438.0551.
-Bromo-N-(2,3-difluoro-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-
-yl)benzyl)-6-(1-fluoroethyl)pyrimidin-4-amine (U14). White solid,
6.68 (s, 1H, Pyrimidine-H), 7.54 (t, J = 7.2 Hz, 1H, Ar-H), 7.84 (d, J
= 10.2 Hz, 1H, Ar-H), 7.89 (d, J = 7.8 Hz, 1H, Ar-H), 8.64 (s, 1H,
5
1
3
3
Pyrimidine-H). C NMR (CDCl , 150 MHz) δ: 39.1, 109.8, 111.4,
3
1
m.p. 128−129 °C, yield 58.6%; H NMR (CDCl , 600 MHz) δ: 1.67
(
112.3 (t, JC‑F = 240.0 Hz, -CHF ), 115.0 (d, J = 24.1 Hz, -CHF ),
3
2
C‑F
2
2
dd, J = 24.0 Hz, 6.6 Hz, 3H, -CH ), 4.90 (d, J = 6.6 Hz, 2H, -CH ),
116.5 (q, JC‑F = 272.1 Hz, -CF ), 123.7, 129.0, 128.2 (d, J = 7.8
3
2
3 C‑F
5
.83−5.96 (m, 1H, -CH), 6.00−6.04 (m, 1H, -NH), 7.32 (t, J = 7.2
Hz), 142.0, 155.5, 157.6, 161.9, 168.0. HRMS m/z (ESI): Calculated
+
Hz, 1H, Ar-H), 7.82 (t, J = 6.6 Hz, 1H, Ar-H), 8.56 (s, 1H,
for C H F N O ([M + H] ): 390.0784, found 390.0784.
1
5
9
6
5
Pyrimidine-H). 13C NMR (CDCl , 150 MHz) δ: 19.3 (d, J = 24.2
3
C‑F
5-Bromo-6-(difluoromethyl)-N-((5-(5-(trifluoromethyl)-1,2,4-oxa-
Hz, -CHFCH ), 39.1, 87.8, 89.0, 102.5, 112.4, 114.5 (d, J = 21.3
Hz, Ar-F), 116.5 (q, J = 272.1 Hz, -CF ), 124.9 (d, J = 4.05 Hz,
Ar-F), 131.4 (d, J = 31.8 Hz), 145.3, 150.0, 156.7, 158.6, 161.9,
diazol-3-yl)pyridin-2-yl)methyl)pyrimidin-4-amine (U21). White
3
C‑F
1
solid, m.p. 148−149 °C, yield 55.4%; H NMR (CDCl , 600 MHz)
C‑F
3
C‑F
3
2
δ: 4.92 (d, J = 4.8 Hz, 2H, -CH ), 6.77 (t, J = 53.4 Hz, 1H, -CHF ),
C‑F
2
2
1
65.3. HRMS m/z (ESI): Calculated for C H BrF N O ([M +
7.50 (d, J = 8.4 Hz, 1H, Py-H), 8.40−8.42 (m, 1H, Py-H), 8.60 (s,
1
6
10
6
5
+
13
H] ): 482.0046, found 482.0047.
-Bromo-6-(difluoromethyl)-N-(4-(5-(trifluoromethyl)-1,2,4-oxa-
diazol-3-yl)benzyl)pyrimidin-4-amine (U15). White solid, m.p. 95
1H, Pyrimidine-H), 9.35 (d, J = 1.8 Hz, 1H, Py-H). C NMR
5
(CDCl , 150 MHz) δ: 46.1, 103.1, 112.3 (t, J = 240.0 Hz, -CHF2),
3
C
‑
F
116.5 (q, JC‑F = 272.1 Hz, -CF ), 120.4, 122.2, 135.7, 148.2, 154.0,
3
1
2
−
96 °C, yield 52.3%; H NMR (CDCl , 600 MHz) δ: 4.86 (d, J = 5.4
156.8, 159.3 (d, J = 73.1 Hz), 161.9, 167.1. HRMS m/z (ESI):
Calculated for C H BrF N O ([M + H] ): 450.9936, found
3
C‑F
+
Hz, 2H, -CH ), 6.12−6.19 (m, 1H, -NH), 6.74 (t, J = 53.4 Hz, 1H,
2
14
8
5
6
-
CHF ), 7.49 (d, J = 8.4 Hz, 2H, Ar-H), 8.11 (d, J = 8.4 Hz, 2H, Ar-
450.9945.
2
1
3
H), 8.59 (s, 1H, Pyrimidine-H). C NMR (CDCl , 150 MHz) δ:
5-Chloro-6-(difluoromethyl)-N-((5-(5-(trifluoromethyl)-1,2,4-oxa-
3
4
5.1, 102.7, 112.3 (t, JC‑F = 240.0 Hz, -CHF ), 116.5 (q, J = 272.1
diazol-3-yl)pyridin-2-yl)methyl)pyrimidin-4-amine (U22). White
2
C‑F
2
1
Hz, -CF ), 124.4, 128.2 (d, J = 7.8 Hz), 142.0, 154.5, 156.8, 159.0,
solid, m.p. 130−131 °C, yield 56.1%; H NMR (CDCl , 600 MHz)
3
C‑F
3
6
972
J. Agric. Food Chem. 2021, 69, 6968−6980