Water → N-(3-fluoro-4-methylphenyl)-7-({2-[(methylamino)carbonyl]-pyridin-4-yl}oxy)-3,4-dihydroisoquinoline-2(1H)-carboxamide

HRID 1640224Notes

Reaction equation

HRID 1640224 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[CH:10]=[C:9]([O:11][C:12]2[CH:21]=[C:20]3[C:15]([CH2:16][CH2:17][NH:18][CH2:19]3)=[CH:14][CH:13]=2)[CH:8]=[CH:7][N:6]=1)=[O:4].[F:22][C:23]1[CH:28]=[C:27]([N:29]=[C:30]=[O:31])[CH:26]=[CH:25][C:24]=1[CH3:32].O>CN(C=O)C>[F:22][C:23]1[CH:28]=[C:27]([NH:29][C:30]([N:18]2[CH2:17][CH2:16][C:15]3[C:20](=[CH:21][C:12]([O:11][C:9]4[CH:8]=[CH:7][N:6]=[C:5]([C:3]([NH:2][CH3:1])=[O:4])[CH:10]=4)=[CH:13][CH:14]=3)[CH2:19]2)=[O:31])[CH:26]=[CH:25][C:24]=1[CH3:32]

Participants

5

Reactant 3

HCID 962WaterHCID 27373983-Fluoro-4-methylphenyl isocyanateHCID 58902413N-methyl-4-(1,2,3,4-tetrahydroisoquinolin-7-yloxy)pyridine-2-carboxamide

Product 1

HCID 58902290N-(3-fluoro-4-methylphenyl)-7-({2-[(methylamino)carbonyl]-pyridin-4-yl}oxy)-3,4-dihydroisoquinoline-2(1H)-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-methyl-4-(1,2,3,4-tetrahydroisoquinolin-7-yloxy)pyridine-2-carboxamide (34 mg, 0.12 mmol) in DMF (1 mL) was added to 2-fluoro-4isocyanato-1-methylbenzene (21.8 mg, 0.144 mmol). The reaction mixture was allowed to stir for 24 h. Water added and the resulting solid was separated and purified by reverse phase HPLC to N-(3-fluoro-4-methylphenyl)-7-({2-[(methylamino)carbonyl]-pyridin-4-yl}oxy)-3,4-dihydroisoquinoline-2(1H)-carboxamide (32 mg, 61%). LCMS: (AA) ES+) 435.5.

Workup

  1. customthe resulting solid was separated
  2. custompurified by reverse phase HPLC to N-(3-fluoro-4-methylphenyl)-7-({2-[(methylamino)carbonyl]-pyridin-4-yl}oxy)-3,4-dihydroisoquinoline-2(1H)-carboxamide (32 mg, 61%)

Sources & evidence

ORD record
ord-92b88351ad104bc393954680d611d3a8
Source dataset
uspto-grants-2012_02
Patent number
US08110687B2

Reaction notes

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