Water → N-[1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropylmethyl]-2,6-difluoro-benzamide

HRID 878461노트

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HRID 878461 반응식
[Br:1][C:2]1[CH:3]=[C:4]([Cl:13])[C:5]([C:8]2([CH2:11][NH2:12])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.C(N(CC)CC)C.[F:21][C:22]1[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:23]=1[C:24](Cl)=[O:25].O>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]([Cl:13])[C:5]([C:8]2([CH2:11][NH:12][C:24](=[O:25])[C:23]3[C:22]([F:21])=[CH:30][CH:29]=[CH:28][C:27]=3[F:31])[CH2:9][CH2:10]2)=[N:6][CH:7]=1

참가 물질

6

반응물 4

HCID 962WaterHCID 8471TriethylamineHCID 874382,6-Difluorobenzoyl chlorideHCID 89544163(1-(5-Bromo-3-chloropyridin-2-yl)cyclopropyl)methanamine

생성물 1

HCID 89544494N-[1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropylmethyl]-2,6-difluoro-benzamide수율 84.8%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

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온도
0 °C

실험 절차

570 mg of C-[1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropyl]-methylamine (step 3) was dissolved in 8 ml of dichloromethane and cooled to 0° C. 441 mg of triethylamine was added, followed by dropwise addition of a solution of 385 mg of 2,6-difluorobenzoyl chloride in 2 ml of dichloromethane. The reaction mixture was stirred at ambient temperature for 1 hour. Water was added and the reaction mixture was extracted twice with dichloromethane. The organic phase was dried over sodium sulfate, filtered and concentrated. 1095 mg of crude material was obtained as a pale brown sticky oil. This residue was purified by chromatography on silica gel with cyclohexane/ethyl acetate (3:1) as a eluent. Thus, 742 mg of N-[1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropylmethyl]-2,6-difluoro-benzamide was obtained as a yellow sticky oil. 1H-NMR (CDCl3): 8.47 ppm (s, 1H), 7.86 ppm (s, 1H), 7.33 ppm (m, 1H), 6.90 ppm (t, 2H), 6.30 ppm (s, 1H, broad), 3.71 ppm (d, 2H), 1.09 ppm (m, 4H).

후처리

  1. extractionthe reaction mixture was extracted twice with dichloromethane
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custom1095 mg of crude material was obtained as a pale brown sticky oil
  6. customThis residue was purified by chromatography on silica gel with cyclohexane/ethyl acetate (3:1) as a eluent

출처 및 근거

ORD 기록
ord-81d53c1efa0c4d398a22c854ae5a6395
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08987465B2

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