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

HRID 578865ノート

反応式

HRID 578865 の反応式
[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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-d443e200b3db493fb450d122ac21dec7
出典データセット
uspto-grants-2015_05
特許番号
US09040708B2

反応ノート

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