2,6-Difluorobenzoyl chloride → HCID 59513743, compound

HRID 1159988Notes

Reaction equation

HRID 1159988 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:9]2[C:17]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]([NH:24][C:25]4[CH:26]=[C:27]5[C:31](=[CH:32][CH:33]=4)[CH2:30][CH:29]([N:34]([CH3:36])[CH3:35])[CH2:28]5)[N:19]=3)=[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][N:11]3[N:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].[F:37][C:38]1[CH:46]=[CH:45][CH:44]=[C:43]([F:47])[C:39]=1[C:40](Cl)=[O:41]>C1COCC1.C(Cl)Cl>[CH3:35][N:34]([CH3:36])[CH:29]1[CH2:28][C:27]2[C:31](=[CH:32][CH:33]=[C:25]([NH:24][C:20]3[N:19]=[C:18]([C:17]4[C:9]([C:4]5[CH:5]=[CH:6][C:7]([F:8])=[C:2]([NH:1][C:40](=[O:41])[C:39]6[C:38]([F:37])=[CH:46][CH:45]=[CH:44][C:43]=6[F:47])[CH:3]=5)=[N:10][N:11]5[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=45)[CH:23]=[CH:22][N:21]=3)[CH:26]=2)[CH2:30]1

Participants

5

Reactant 2

HCID 874382,6-Difluorobenzoyl chlorideHCID 59511395HCID 59511395, compound

Product 1

HCID 59513743HCID 59513743, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of {4-[2-(3-amino-4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-pyrimidinyl}[2-(dimethylamino)-2,3-dihydro-1H-inden-5-yl]amine (80 mg, 0.17 mmol) in THF (3 mL) was added TEA (25 μL, 0.25 mmol) and 2,6-difluorobenzoyl chloride (22 μL, 0.18 mmol). The reaction was stirred at rt for 2 h, and the reaction was diluted with 30 mL DCM and adsorbed onto silica. The crude product was purified by flash chromatography and reversed-phase HPLC to generate, after lyophilization, the title compound as a TFA salt (38 mg, 37% yield). 1H NMR (400 MHz, d6-DMSO): δ 10.84 (s, 1H), 9.59 (s, 1H), 8.88 (d, J=6.7 Hz, 1H), 8.44 (d, J=8.4 Hz, 1H), 8.30 (d, J=5.3 Hz, 1H), 8.24 (d, J=7.0 Hz, 1H), 7.75 (s, 1H), 7.58-7.62 (m, 1H), 7.41-7.52 (m, 4H), 7.24 (t, J=8.0 Hz, 2H), 7.13-7.16 (m, 2H), 6.61 (d, J=5.3 Hz, 1H), 4.04-4.12 (m, 1H), 3.22-3.28 (m, 2H), 3.06-3.12 (m, 2H), 2.82 (s, 6H). MS (ESI) m/z=620 [M+H]+.

Workup

  1. customThe crude product was purified by flash chromatography and reversed-phase HPLC

Sources & evidence

ORD record
ord-74c82ccb457a4e9eb48580f6ac8d64d8
Source dataset
uspto-grants-2010_10
Patent number
US07812022B2

Reaction notes

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