2,6-Difluoroaniline → N-(2,6-difluorophenyl)-3-(3-{2-[(3-{[2-(dimethylamino)ethyl]oxy}-2-methylphenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)benzamide

HRID 419324Notes

Reaction equation

HRID 419324 reaction equation
[CH3:1][N:2]([CH3:39])[CH2:3][CH2:4][O:5][C:6]1[C:7]([CH3:38])=[C:8]([NH:12][C:13]2[N:18]=[C:17]([C:19]3[N:23]4[CH:24]=[CH:25][CH:26]=[CH:27][C:22]4=[N:21][C:20]=3[C:28]3[CH:29]=[C:30]([CH:35]=[CH:36][CH:37]=3)[C:31](OC)=[O:32])[CH:16]=[CH:15][N:14]=2)[CH:9]=[CH:10][CH:11]=1.[F:40][C:41]1[CH:47]=[CH:46][CH:45]=[C:44]([F:48])[C:42]=1[NH2:43].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[F:40][C:41]1[CH:47]=[CH:46][CH:45]=[C:44]([F:48])[C:42]=1[NH:43][C:31](=[O:32])[C:30]1[CH:35]=[CH:36][CH:37]=[C:28]([C:20]2[N:21]=[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]3[C:19]=2[C:17]2[CH:16]=[CH:15][N:14]=[C:13]([NH:12][C:8]3[CH:9]=[CH:10][CH:11]=[C:6]([O:5][CH2:4][CH2:3][N:2]([CH3:1])[CH3:39])[C:7]=3[CH3:38])[N:18]=2)[CH:29]=1

Participants

5

Reactant 3

HCID 796472,6-DifluoroanilineHCID 2724254Sodium bis(trimethylsilyl)amideHCID 59452717Methyl 3-(3-{2-[(3-{[2-(dimethylamino)ethyl]oxy}-2-methylphenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)benzoate

Product 1

HCID 59452834N-(2,6-difluorophenyl)-3-(3-{2-[(3-{[2-(dimethylamino)ethyl]oxy}-2-methylphenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)benzamideYield 98.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 3-(3-{2-[(3-{[2-(dimethylamino)ethyl]oxy}-2-methylphenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)benzoate (60.0 mg, 0.115 mmol) and 2,6-difluoroaniline (0.0350 mL, 0.345 mmol) in THF (5 mL) was added sodium bis(trimethylsilyl)amide (0.46 mL, 0.460 mmol, 1.0 M solution in THF), and the reaction mixture was stirred for 5 min at rt. The mixture was quenched with saturated NaHCO3, diluted with DCM, and the organic layer was separated. The solvent was removed and the crude material was purified via silica gel chromatography to give 70 mg (98% yield) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 10.24 (s, 1H), 9.36 (d, J=6.6 Hz, 1H), 9.08 (s, 1H), 8.32 (s, 1H), 8.20 (d, J=5.3 Hz, 1H), 8.06 (d, J=7.9 Hz, 1H), 7.83 (d, J=7.7 Hz, 1H), 7.72 (d, J=9.0 Hz, 1H), 7.62 (t, J=7.8 Hz, 1H), 7.42 (t, 2H), 7.12-7.28 (m, J=8.0, 8.0 Hz, 3H), 7.03 (d, J=7.5 Hz, 1H), 6.87 (d, 2H), 6.48 (d, J=5.3 Hz, 1H), 4.07 (t, J=5.8 Hz, 2H), 2.66 (t, J=5.7 Hz, 2H), 2.22 (s, 6H), 2.07 (s, 3H). MS (APCI+) m/z 620 [M+H].

Workup

  1. customThe mixture was quenched with saturated NaHCO3
  2. additiondiluted with DCM
  3. customthe organic layer was separated
  4. customThe solvent was removed
  5. customthe crude material was purified via silica gel chromatography

Sources & evidence

ORD record
ord-1fbc69071cfb403bb0ec03201d79383c
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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