2,5-Difluorobenzoyl chloride → 2,5-Difluoro-N-[3-(3-{2-[(2-methyl-1,2,3,4-tetrahydro-7-isoquinolinyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]benzamide

HRID 1160000Notes

Reaction equation

HRID 1160000 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24]4[CH:33]=[C:32]5[C:27]([CH2:28][CH2:29][N:30]([CH3:34])[CH2:31]5)=[CH:26][CH:25]=4)[N:18]=3)=[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[F:35][C:36]1[CH:44]=[CH:43][C:42]([F:45])=[CH:41][C:37]=1[C:38](Cl)=[O:39]>C(Cl)Cl>[F:35][C:36]1[CH:44]=[CH:43][C:42]([F:45])=[CH:41][C:37]=1[C:38]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[C:16]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24]4[CH:33]=[C:32]5[C:27]([CH2:28][CH2:29][N:30]([CH3:34])[CH2:31]5)=[CH:26][CH:25]=4)[N:18]=3)=[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][N:10]3[N:9]=2)[CH:3]=1)=[O:39]

Participants

4

Reactant 2

HCID 5880822,5-Difluorobenzoyl chlorideHCID 59511387N-{4-[2-(3-Aminophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinyl}-2-methyl-1,2,3,4-tetrahydro-7-isoquinolinamine

Product 1

HCID 116643002,5-Difluoro-N-[3-(3-{2-[(2-methyl-1,2,3,4-tetrahydro-7-isoquinolinyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]benzamideYield 51%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of N-{4-[2-(3-aminophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinyl}-2-methyl-1,2,3,4-tetrahydro-7-isoquinolinamine (96 mg, 0.21 mmol) and TEA (45 μL, 0.32 mmol) in DCM (2 mL) was added 2,5-difluorobenzoyl chloride (28 μL, 0.23 mmol). After 16 h at rt, the reaction mixture was adsorbed onto silica and purified by column chromatography to generate the title compound in 51% yield (63 mg, 0.11 mmol). 1H NMR (400 MHz, d6-DMSO) δ 10.65 (s, 1H), 9.44 (s, 1H), 8.87 (d, J=6.9 Hz, 1H), 8.47 (d, J=9.3 Hz, 1H), 8.26 (d, J=5.7 Hz, 1H), 8.05 (s, 1H), 7.86 (d, J=8.4 Hz, 1H), 7.34-7.55 (m, 8H), 7.13 (t, J=6.9 Hz, 1H), 6.99 (d, J=8.4 Hz, 1H), 6.51 (d, J=5.3 Hz, 1H), 3.41 (s, 2H), 2.76 (t, J=5.7 Hz, 2H), 2.58-2.60 (m, 2H), 2.33 (s, 3H). HRMS=588.23178 (calculated for C34H27F2N7O=587.6313).

Workup

  1. custompurified by column chromatography

Sources & evidence

ORD record
ord-10b8c9b190574abc92bf8e4d59f2a8ef
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Reaction notes

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