Methylamine → 4-(4-{5-[(4-Fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-n-methylbenzamide hydrochloride salt

HRID 241189ノート

反応式

HRID 241189 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10]([N:16]3[CH2:22][C:21]4[CH:23]=[C:24]([C:27]5[CH:35]=[CH:34][C:30]([C:31]([Cl:33])=[O:32])=[CH:29][CH:28]=5)[CH:25]=[CH:26][C:20]=4[O:19][CH2:18][CH2:17]3)=[N:11][CH:12]=[N:13][C:14]=2[CH3:15])=[CH:4][CH:3]=1.[CH3:36][NH2:37]>C1COCC1>[ClH:33].[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10]([N:16]3[CH2:22][C:21]4[CH:23]=[C:24]([C:27]5[CH:35]=[CH:34][C:30]([C:31]([NH:37][CH3:36])=[O:32])=[CH:29][CH:28]=5)[CH:25]=[CH:26][C:20]=4[O:19][CH2:18][CH2:17]3)=[N:11][CH:12]=[N:13][C:14]=2[CH3:15])=[CH:4][CH:3]=1

参加物

4

反応物 2

HCID 6329MethylamineHCID 866478534-(4-{5-[(4-Fluorophenyl)-methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)benzoyl chloride

生成物 1

HCID 687739464-(4-{5-[(4-Fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-n-methylbenzamide hydrochloride salt収率 53%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 4-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)benzoyl chloride (30.0 mg, 62 μmol) in THF (5 mL) was added drop wise 40% aqueous methylamine (0.25 mL, 2.0 mmol) at 0° C. The reaction mixture was stirred at room temperature for 1 h, at which time it was concentrated. The resulting solid was dissolved in chloroform (30 mL), washed with water (20 mL), and dried over sodium sulfate then filtered. To the solution was then added drop wise 4N hydrogen chloride in dioxane (0.25 mL) and the mixture concentrated. The residue was taken up in 4:1 water and acetonitrile (2 mL) and lyophilized to give 4-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-N-methylbenzamide hydrochloride salt (16.5 mg, 53% yield) as a white powder. 1H NMR (400 MHZ, DMSO-d6): 8.79 (s, 1H), 8.53 (dd, 1H), 7.97 (d, 2H), 7.65 (d, 2H), 7.57 (d, 1H), 7.30-7.13 (m, 5H), 6.97 (d, 1H), 4.92 (s, 1H), 4.35 (br 2H), 4.04-3.97 (m, 4H), 3.83 (d, 3H), 2.24 (s, 3H); MS (EI) for C29H27FN4O2: 483 (MH+).

後処理

  1. concentrationwas concentrated
  2. dissolutionThe resulting solid was dissolved in chloroform (30 mL)
  3. washwashed with water (20 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationthen filtered
  6. additionTo the solution was then added drop wise 4N hydrogen chloride in dioxane (0.25 mL)
  7. concentrationthe mixture concentrated

出典と根拠

ORDレコード
ord-fbcc1231c0aa4b44ae32c6c8972b3ad5
出典データセット
uspto-grants-2014_02
特許番号
US08648066B2

反応ノート

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