Trifluoroacetic acid → 4-(2-(5-Fluoro-6-methoxypyridin-3-ylamino)pyridin-3-YL)-6-methyl-1,3,5-triazin-2-amine
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[C:16]([C:17]3[N:22]=[C:21]([CH3:23])[N:20]=[C:19]([N:24](CC4C=CC(OC)=CC=4)CC4C=CC(OC)=CC=4)[N:18]=3)=[CH:15][CH:14]=[CH:13][N:12]=2)[CH:5]=[N:6][C:7]=1[O:8][CH3:9].C(O)(C(F)(F)F)=O>>[F:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[C:16]([C:17]3[N:22]=[C:21]([CH3:23])[N:20]=[C:19]([NH2:24])[N:18]=3)=[CH:15][CH:14]=[CH:13][N:12]=2)[CH:5]=[N:6][C:7]=1[O:8][CH3:9]Participants
Conditions
- Temperature
- 75 °C
Procedure
4-(2-(5-Fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (232 mg, 0.409 mmol) was treated with TFA (8.0 mL) (Aldrich) and heated at 75° C. with a reflux condenser for 17 h. The TFA was removed in vacuo and the crude product was treated with 2 M NH3 in MeOH resulting in a suspension that was filtered and washed with water to give the desired product in ca. 80% purity. It was then resuspended in MeOH and filtered and washed with 1 N NaOH (aq), MeOH and hexanes and dried to give an olive-colored amorphous solid. It was further purified on the ISCO (12 g column, 1-25% MeOH in DCM) to give 4-(2-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (68.6 mg, 0.210 mmol, 51.3% yield) as a fibrous, yellow amorphous solid. m/z (ESI, +ve ion) 328.1 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 11.95 (1H, s); 8.80 (1H, dd, J=7.8, 2.0 Hz); 8.42 (1H, d, J=2.3 Hz); 8.33-8.40 (2H, m); 7.91 (1H, br. s.); 7.77 (1H, br. s.); 6.94 (1H, dd, J=7.8, 4.7 Hz); 3.94 (3H, s); 2.43 (3H, s).
Workup
- customThe TFA was removed in vacuo
- additionthe crude product was treated with 2 M NH3 in MeOH resulting in a suspension that
- filtrationwas filtered
- washwashed with water
Sources & evidence
- ORD record
- ord-7b0a19f9b78e47b282a2734d8990db05
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08772480B2
Reaction notes
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