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

HRID 241186노트

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HRID 241186 반응식
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

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

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온도
130 °C

실험 절차

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+).

후처리

  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)

출처 및 근거

ORD 기록
ord-163239aa85a14239b0a743f5c7a912cf
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08648066B2

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