Ammonia → HCID 67340322, compound

HRID 2092343Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[C:7]([O:13][C:14]3[C:19]([C:20]4[CH:25]=[CH:24][N:23]=[C:22]([NH:26][CH3:27])[N:21]=4)=[CH:18][CH:17]=[CH:16][N:15]=3)[C:8]([CH3:12])=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.[F:28][C:29]([F:39])([F:38])[O:30][C:31]1[CH:32]=[C:33]([CH:35]=[CH:36][CH:37]=1)[NH2:34].Cl.N>O1CCOCC1.CO>[CH3:12][C:8]1[C:7]([O:13][C:14]2[C:19]([C:20]3[CH:25]=[CH:24][N:23]=[C:22]([NH:26][CH3:27])[N:21]=3)=[CH:18][CH:17]=[CH:16][N:15]=2)=[C:6]2[C:11](=[CH:10][CH:9]=1)[C:2]([NH:34][C:33]1[CH:35]=[CH:36][CH:37]=[C:31]([O:30][C:29]([F:28])([F:38])[F:39])[CH:32]=1)=[N:3][CH:4]=[CH:5]2

Participants

Conditions

Temperature: 170 °C

Procedure

4-(2-(1-Chloro-6-methylisoquinolin-5-yloxy)pyridin-3-yl)-N-methylpyrimidin-2-amine (0.150 g, 0.40 mmol) was suspended in dioxane (1.00 mL) to which mixture was added 3-(trifluoromethoxy)aniline (0.12 ml, 0.79 mmol). 4N HCl in dioxane (1.00 mL) was added and the mixture was stirred. The vessel was sealed and heated to 170° C. in microwave for 15 minutes. The reaction mixture was treated with 2M ammonia in methanol and concentrated directly onto silica gel. The material was chromatographed eluting with a gradient of EtOAc/hexanes (15-100%) followed by trituration of the pure material in EtOAc to afforded 6-methyl-5-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)-N-(3-(trifluoromethoxy)phenyl)isoquinolin-1-amine. MS (M+H)+ 519.

Workup

customThe vessel was sealed
concentrationconcentrated directly onto silica gel
customThe material was chromatographed
washeluting with a gradient of EtOAc/hexanes (15-100%)

Sources & evidence

ORD record: ord-3d38f49966bd472caef9e13a252ad87f
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08440674B2

Reaction notes

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