Ammonia → 2-(6-((2-(3-Chlorophenyl)-6-cyclopropylpyrimidin-4-yl)amino)pyridin-3-yl)acetamide
Reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([NH:14][C:15]3[N:20]=[CH:19][C:18]([CH2:21][C:22]([O:24]CC)=O)=[CH:17][CH:16]=3)[CH:11]=[C:10]([CH:27]3[CH2:29][CH2:28]3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[NH3:30]>>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([NH:14][C:15]3[N:20]=[CH:19][C:18]([CH2:21][C:22]([NH2:30])=[O:24])=[CH:17][CH:16]=3)[CH:11]=[C:10]([CH:27]3[CH2:28][CH2:29]3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1Participants
Conditions
- Temperature
- 100 °C
Procedure
A 10-mL vial was charged with ethyl 2-(6-((2-(3-chlorophenyl)-6-cyclopropylpyrimidin-4-yl)amino)pyridin-3-yl)acetate (0.070 g, 0.17 mmol) and NH3 (4.9 mL, 7N in methanol, 34.2 mmol). The vial was sealed and the resulting mixture was stirred at 100° C. for 23 h. The crude reaction solution concentrated under reduced pressure. The residue was absorbed on silica (2 g) then purified by chromatography on silica using dichloromethane/methanol (10:0 to 9:1) as eluent to afford the title compound (0.029 g, 45%) as a white solid. M.p. 232-235° C. 1H NMR (DMSO-d6, 500 MHz) δ 10.10 (s, 1H), 8.31-8.29 (m, 1H), 8.27 (dt, J=7.5, 2.0 Hz, 1H), 8.19 (d, J=2.0 Hz, 1H), 7.75-7.69 (m, 1H), 7.67 (dd, J=8.5, 2.0 Hz, 1H), 7.60 (br s, 1H), 7.58-7.52 (m, 2H), 7.50 (br s, 1H), 6.93 (br s, 1H), 3.37 (s, 2H), 2.07 (septet, J=4.5 Hz, 1H), 1.14-1.09 (m, 2H); 1.06-1.00 (m, 2H); APCI MS m/z 380 [M+H]+.
Workup
- customThe vial was sealed
- customThe crude reaction solution
- concentrationconcentrated under reduced pressure
- customThe residue was absorbed on silica (2 g)
- customthen purified by chromatography on silica
Sources & evidence
- ORD record
- ord-3389349106e84b80a040a15a1afbf569
- Source dataset
- uspto-grants-2015_12
- Patent number
- US09221843B2
Reaction notes
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