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 419324ノート

反応式

HRID 419324 の反応式
[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

参加物

5

反応物 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

生成物 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)benzamide収率 98.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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].

後処理

  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

出典と根拠

ORDレコード
ord-1fbc69071cfb403bb0ec03201d79383c
出典データセット
uspto-grants-2012_01
特許番号
US08093239B2

反応ノート

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