8
Tetrahedron
ACCEPTED MANUSCRIPT
MHz): δ 8.36 (s, 1H), 6.36 (s, 1H), 5.82-5.73 (m,
ATR-FTIR (neat, cm- 1 ): ν 3080, 2868, 1645, 1569,
2H), 5.19 (d, J = 10.3 Hz, 2H), 5.12 (dd, J = 1.3
and 17.2 Hz, 2H), 4.18-3.95 (broad s, 4H). 1 3 C-
NMR (CDCl3 , 100 MHz): δ 162.3, 159.5, 157.9,
131.8, 117.3, 101.5, 49.8. MS, m/z (relative
intensity): 212 (13), 210 ([M+H]. + , 45), 208 (26),
196 (11), 194 (36), 170 (34), 169 (12), 168 (100),
167 (15), 166 (25), 157 (12), 156 (18), 155 (38),
154 (39), 134 (19), 132 (37), 107 (9), 105 (14), 86
(8), 52 (9).
1406, 1381, 1362, 1112, 974, 736. 1 H-NMR (CDCl3 ,
400 MHz): δ 8.29 (s, 1H), 8.05 (s, 1H), 6.50 (s,
1H), 3.68 (t, J = 4.5 Hz, 2H), 3.56 (t, J = 4.5 Hz,
4H), 3.41 (t, J = 4.5 Hz, 2H). 1 3 C-NMR (CDCl3 , 100
MHz): δ 162.3, 160.9, 160.4, 158.1, 101.8, 44.8,
44.5, 43.5, 39.5. MS, m/z (relative intensity): 228
(11), 226 ([M]. + , 34), 225 (9), 170 (16), 168 (46),
158 (18), 157 (38), 156 (68), 155 (100), 154 (68),
144 (34), 143 (9), 142 (92), 140 (13), 130 (10), 114
(10), 113 (8), 68 (25), 56 (9), 52 (13).
4.7.11. 6-Chloro-N-propylpyrimidin-4-amine (5h).
Yield = 91%. White powder. mp 64-65 °C. GC (80
°C, 6 °C/min): tR 6.89 min. ATR-FTIR (neat, cm- 1 ):
ν 3236, 2964, 2929, 1600, 1570, 1393, 1089, 745.
1 H-NMR (CDCl3 , 400 MHz): δ 8.30 (s, 1H), 6.36 (s,
1H), 3.30-3.23 (broad m, 2H), 2.69 (broad s, 1H),
1.67-1.62 (m, 2H), 0.98 (t, J = 7.4 Hz, 3H). 1 3 C-
NMR (CDCl3 , 100 MHz): δ 163.1, 158.0, 157.9,
101.3, 45.3, 22.2, 11.3. MS, m/z (relative
intensity): 173 (12), 172 ([M+H]. + , 28), 171 ([M]. + ,
30), 170 (24), 158 (11), 156 (32), 144 (34), 143 (9),
142 (100), 131 (23), 130 (8), 129 (72), 115 (6), 10 4
(5), 102 (17), 88 (5), 86 (13), 67 (30), 52 (11).
4.7.16. 4-Chloro-6-(1H-pyrrol-1-yl)pyrimidine4 5
(5m). Yield = 60%. White cristals. mp 95-96 °C.
GC (80 °C,
6 °C/min): tR 7.12 min. ATR-FTIR
(neat, cm- 1 ): ν 3140, 3123, 1567, 1484, 1371, 1056,
724. 1 H-NMR (CDCl3 , 400 MHz): δ 8.76 (s, 1H),
7.52 (t, J = 2.3 Hz, 2H), 7.25 (d, J = 0.6 Hz, 1H),
6.41 (t, J = 2.3 Hz, 2H). 1 3 C-NMR (CDCl3 , 100
MHz): δ 162.2, 158.8, 157.7, 118.2, 113.7, 107.2.
MS, m/z (relative intensity): 181 (33), 180 (12),
179 ([M]. + , 100), 155 (8), 154 (13), 153 (23), 152
(32), 117 (17), 90 (6), 86 (9), 63 (5).
4.7.17. 4-Chloro-6-(1H-imidazol-1-yl)pyrimidine4 7
(5n). Yield = 73%. Yellowish powder. mp 133-135
°C. GC (80 °C, 6 °C/min): tR 8.53 min. ATR-FTIR
(neat, cm- 1 ): ν 3142, 3087, 1568, 1556, 1486, 1132,
1054, 979, 782, 657. 1 H-NMR (CDCl3 , 400 MHz): δ
8.83 (s, 1H), 8.45 (s, 1H), 7.63 (d, J = 2.3 Hz , 1H),
7.38 (d, J = 2.3 Hz , 1H), 7.21 (s, 1H). 1 3 C-NMR
(CDCl3 , 100 MHz): δ 163.0, 159.1, 155.8, 135.4,
132.1, 115.6, 108.5. MS, m/z (relative intensity):
182 (34), 181 (9), 180 ([M]. + , 100), 155 (24), 154
(13), 153 (70), 118 (26), 86 (10), 52 (6).
4.7.18. 4-(2-Chloropyrimidin-4-yl)-morpholine4 8
(7a). Yield = 84%. White powder. mp 75-76 °C.
GC (60 °C, 6 °C/min): tR 14.77 min. ATR-FTIR
(neat, cm- 1 ): ν 3090, 2971, 2866, 1575, 1507, 1335,
1112, 1022, 980, 776. 1 H-NMR (CDCl3 , 400 MHz):
δ 8.08 (d, J = 6.1 Hz , 1H), 6.39 (d, J = 6.1 Hz ,
1H), 3.78 (t, J = 4.5 Hz , 4H), 3.65 (broad s, 4H).
1 3 C-NMR (CDCl3 , 100 MHz): δ 162.8, 160.8, 157.5,
101.1, 66.3, 44.2. MS, m/z (relative intensity): 201
(26), 200 (28), 199 ([M]. + , 74), 184 (33), 171 (23),
170 (41), 169 (23), 168 (100), 158 (19), 156 (63),
154 (31), 144 (20), 142 (56), 141 (18), 116 (15),
114 (45), 86 (14), 79 (49), 52 (20).
4.7.19. 2-Chloro-4-(pyrrolidin-1-yl)pyrimidine4 9
(7c). Yield = 75%. White powder. mp 72-73 °C.
GC (80 °C, 6 °C/min): tR 16.51 min. ATR-FTIR
(neat, cm- 1 ): ν 3082, 2974, 2872, 1578, 1519, 1313,
1148, 818, 779, 713. 1 H-NMR (CDCl3 , 400 MHz): δ
8.14 (d, J = 5.1 Hz , 1H), 6.45 (d, J = 5.1 Hz , 1H),
3.54 (d, J = 6.8 Hz , 4H), 1.98-1.95 (m, 4H). 1 3 C-
NMR (CDCl3 , 100 MHz): δ 160.9, 160.1, 158.7,
108.2, 46.8, 25.4. MS, m/z (relative intensity): 184
(11), 183 ([M]. + , 49), 182 (8), 157 (16), 156 (52),
155 (64), 154 (100), 142 (6), 141 (8), 130 (6), 129
(6), 128 (8), 94 (6), 93 (6), 86 (7), 79 (8), 52 (9).
4.7.12. 6-Chloro-N-(4-methoxyphenyl)pyrimidin-4-
amine4 5 (5i). Yield = 91%. Off-white powder. mp
135-136 °C. GC (80 °C, 6 °C/min): tR 16.47 min.
ATR-FTIR (neat, cm- 1 ): ν 3231, 2959, 1567, 1507,
1250, 1094, 828, 744. 1 H-NMR (CDCl3 , 400 MHz):
δ 8.39 (s, 1H), 7.47 (broad s, 1H), 7.20 (d, J = 8.8
Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 6.52 (s, 1H),
3.84 (s, 3H). 1 3 C-NMR (CDCl3 , 100 MHz): δ 162.6,
160.7, 158.3, 158.0, 129.2, 126.2, 115.1, 102.3,
55.6. MS, m/z (relative intensity): 238 (5), 237
(33), 236 ([M+H]. + , 38), 235 ([M]. + , 100), 234 (68),
222 (22), 221 (13), 220 (61), 194 (5), 192 (13), 191
(6), 165 (7), 158 (7), 157 (9), 108 (5), 80 (6).
4.7.13. 1-(6-Chloropyrimidin-4-yl)indoline4 6
(5j).
Yield = 89%. Off-white powder. mp 151-153 °C.
GC (80 °C, 6 °C/min): tR 17.53 min. ATR-FTIR
(neat, cm- 1 ): ν 2886, 1560, 1514, 1112, 984, 757.
1 H-NMR (CDCl3 , 400 MHz): δ 8.58 (s, 1H), 8.37 (d,
J = 7.8 Hz, 1H), 7.24 (d, J = 7.6 Hz, 2H), 7.02 (t, J
= 7.4 Hz, 1H), 6.60 (s, 1H), 4.00 (t, J = 8.5 Hz,
2H), 1.41 (t, J = 8.5 Hz, 2H). 1 3 C-NMR (CDCl3 , 100
MHz): δ 159.9, 159.6, 157.7, 142.7, 131.9, 127.5,
124.9, 123.2, 116.4, 103.6, 48.6, 27.4. MS, m/z
(relative intensity): 233 (32), 232 ([M+H]. + , 46),
231 ([M]. + , 100), 230 (84), 215 (15), 204 (8), 196
(17), 194 (6), 169 (19), 168 (20), 167 (13), 143
(10), 142 (7), 140 (9), 119 (6), 118 (57), 117 (20),
115 (8), 91 (16), 89 (8).
4.7.14. (S)-Methyl
1-(6-chloropyrimidin-4-yl)
pyrrolidine-2-carboxylate3 3 (5k). Yield = 81%.
Colorless oil. GC (80 °C, 6 °C/min): tR 14.71 min.
ATR-FTIR (neat, cm- 1 ): ν 2953, 2876, 1739, 1570,
1526, 1494, 1170, 1157, 1102, 1020, 969, 747. 1 H-
NMR (CDCl3 , 400 MHz): δ 8.31 (s, 1H), 6.36 (s,
1H), 4.68-4.65 (m, 1H), 3.71 (s, 3H), 3.57-3.53 (m,
1H), 3.46-3.40 (m, 1H), 2.29-2.00 (m, 4H). 1 3 C-
NMR (CDCl3 , 100 MHz): δ 172.9, 160.5, 159.4,
157.9, 102.3, 59.5, 52.3, 46.7, 29.7, 23.9. MS, m/z
(relative intensity): 243 (5), 241 ([M]. + , 14), 184
(31), 183 (9), 182 (100), 167 (5).
4.7.20. 4-(6-Chloropyrazin-2-yl)morpholine3 0 (9a).
Yield = 92%. Off-white powder. mp 114-115 °C.
GC (80 °C,
6 °C/min): tR 9.51 min. ATR-FTIR
(neat, cm- 1 ): ν 2966, 2870, 1258, 1138, 1111, 962.
1 H-NMR (CDCl3 , 400 MHz): δ 7.96 (s, 1H), 7.83 (s,
1H), 3.80 (t, J = 4.8 Hz, 4H), 3.56 (t, J = 4.8 Hz,
4H). 1 3 C-NMR (CDCl3 , 100 MHz): δ 154.1, 146.7,
131.1, 127.5, 66.3, 44.5. MS, m/z (relative
4.7.15. 4-(6-Chloropyrimidin-4-yl)piperazine-1-
carbaldehyde4 5 (5l). Yield = 81%. White powder.
mp 93-95 °C. GC (80 °C, 6 °C/min): tR 16.98 min.