Water → N-[[1-(5-bromo-3-chloro-2-pyridyl)cyclopropyl]methyl]-3-(trifluoromethyl)pyridine-2-carboxamide

HRID 578865노트

반응식

HRID 578865 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]([F:33])([F:32])[C:23]1[C:24]([C:29](Cl)=[O:30])=[N:25][CH:26]=[CH:27][CH:28]=1.O>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]([Cl:13])[C:5]([C:8]2([CH2:11][NH:12][C:29]([C:24]3[C:23]([C:22]([F:33])([F:21])[F:32])=[CH:28][CH:27]=[CH:26][N:25]=3)=[O:30])[CH2:9][CH2:10]2)=[N:6][CH:7]=1

참가 물질

6

반응물 4

HCID 962WaterHCID 8471TriethylamineHCID 450819483-(Trifluoromethyl)pyridine-2-carbonyl chlorideHCID 89544163(1-(5-Bromo-3-chloropyridin-2-yl)cyclopropyl)methanamine

생성물 1

HCID 71558839N-[[1-(5-bromo-3-chloro-2-pyridyl)cyclopropyl]methyl]-3-(trifluoromethyl)pyridine-2-carboxamide수율 96.3%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

350 mg of C-[1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropyl]-methylamine (step 3 of PREPARATION EXAMPLE 3) was dissolved in 7 ml of dichloromethane and 0.37 ml of triethylamine was added at ambient temperature. Then a solution of 308 mg 3-(trifluoromethyl)pyridine-2-carbonyl chloride (1.10 eq, 1.47 mmol, 0.) in 3 ml of dichloromethane was added dropwise. The reaction mixture was stirred at ambient temperature for 14 hours, then water was added, the phases were separated and the water phase was extracted with dichloromethane. The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated. Crude material was obtained as a brown sticky solid, which was purified by flash chromatography on silica gel with cyclohexane/ethyl acetate (2:1) as a solvent. Thus, 560 mg of N-[[1-(5-bromo-3-chloro-2-pyridyl)cyclopropyl]methyl]-3-(trifluoromethyl)pyridine-2-carboxamide was obtained as a sticky solid. 1H-NMR (CDCl3): 8.70 ppm (d, 1H), 8.45 ppm (d, 1H), 8.12 ppm (d, 1H), 7.90 ppm (s, 1H, broad), 7.83 ppm (d, 1H), 7.52 ppm (m, 1H), 3.73 ppm (d, 2H), 1.10 ppm (m, 4H).

후처리

  1. customthe phases were separated
  2. extractionthe water phase was extracted with dichloromethane
  3. dry with materialThe organic phase was dried with anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customCrude material was obtained as a brown sticky solid, which
  7. customwas purified by flash chromatography on silica gel with cyclohexane/ethyl acetate (2:1) as a solvent

출처 및 근거

ORD 기록
ord-d443e200b3db493fb450d122ac21dec7
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09040708B2

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