Dimethylformamide → Methyl 4-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)benzoate

HRID 241186ノート

反応式

HRID 241186 の反応式
Cl.[O:2]1[C:8]2[CH:9]=[CH:10][C:11](OC(=O)C3C=CC=CC=3)=[CH:12][C:7]=2[CH2:6][NH:5][CH2:4][CH2:3]1.Cl[C:23]1[C:28]([CH2:29][C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)=[C:27]([CH3:37])[N:26]=[CH:25][N:24]=1.[C:38](=[O:41])([O-])[O-].[K+].[K+].CN([CH:47]=[O:48])C>C(OCC)(=O)C>[F:36][C:33]1[CH:34]=[CH:35][C:30]([CH2:29][C:28]2[C:23]([N:5]3[CH2:6][C:7]4[CH:12]=[C:11]([C:7]5[CH:12]=[CH:11][C:10]([C:38]([O:48][CH3:47])=[O:41])=[CH:9][CH:8]=5)[CH:10]=[CH:9][C:8]=4[O:2][CH2:3][CH2:4]3)=[N:24][CH:25]=[N:26][C:27]=2[CH3:37])=[CH:31][CH:32]=1

参加物

6

反応物 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 866478404-Chloro-5-(4-fluorobenzyl)-6-methylpyrimidineHCID 86647851(2,3,4,5-Tetrahydro-1,4-benzoxazepin-7-yl)benzoate hydrochloride

生成物 1

HCID 49839712Methyl 4-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)benzoate収率 50%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

反応条件

温度
130 °C

実験手順

A suspension of -(2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)benzoate hydrochloride (1.30 g, 4.14 mmol), 4-chloro-5-[(4-fluorophenyl)methyl]-6-methylpyrimidine (reagent preparation 5) (0.98 g, 4.14 mmol), and potassium carbonate (1.71 g, 12.4 mmol) in DMF (20 mL) was heated to 130° C. for 18 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (40 mL), and then washed with water (50 mL) and brine (20 mL). The organic layer was dried over sodium sulfate then filtered and concentrated. Column chromatography on silica (gradient 10 to 20% ethyl acetate in hexane) followed by recrystallization from 1:1 ethyl acetate and ether (40 mL) provided methyl 4-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)benzoate (1.05 g, 50% yield) as a white solid. 1H NMR (400 MHZ, DMSO-D6): 8.48 (s, 1H), 8.01 (d, 2H), 7.62 (d, 2H), 7.56 (dd, 1H), 7.11 (d, 4H), 7.02 (d, 1H), 6.91 (d, 1H), 4.52 (s, 2H), 4.32 (m, 2H), 3.95 (s, 2H), 3.90 (s, 3H), 3.76 (m, 2H), 2.13 (s, 3H); MS (EI) for C29H26FN3O3: 484 (MH+).

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed with water (50 mL) and brine (20 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationthen filtered
  5. concentrationconcentrated
  6. customColumn chromatography on silica (gradient 10 to 20% ethyl acetate in hexane) followed by recrystallization from 1:1 ethyl acetate and ether (40 mL)

出典と根拠

ORDレコード
ord-163239aa85a14239b0a743f5c7a912cf
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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