Citric Acid → 5-bromo-6-(4-chloro-phenyl)-3-trifluoromethyl-pyrazine-2-carboxylic acid ((1R,2R)-2-hydroxy-cyclohexyl)-amide

HRID 416468노트

반응식

HRID 416468 반응식
[Br:1][C:2]1[N:3]=[C:4]([C:18]([F:21])([F:20])[F:19])[C:5]([C:15](O)=[O:16])=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=1.ClC(N(C)C)=C(C)C.[NH2:30][C@@H:31]1[CH2:36][CH2:35][CH2:34][CH2:33][C@H:32]1[OH:37].C(N(C(C)C)C(C)C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>ClCCl.C(OCC)(=O)C>[OH:37][C@@H:32]1[CH2:33][CH2:34][CH2:35][CH2:36][C@H:31]1[NH:30][C:15]([C:5]1[C:4]([C:18]([F:20])([F:21])[F:19])=[N:3][C:2]([Br:1])=[C:7]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)[N:6]=1)=[O:16]

참가 물질

8

반응물 5

HCID 311Citric AcidHCID 81531DiisopropylethylamineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 735777(1R,2R)-2-AminocyclohexanolHCID 462210845-Bromo-6-(4-chloro-phenyl)-3-trifluoromethyl-pyrazine-2-carboxylic acid

생성물 1

HCID 462210855-bromo-6-(4-chloro-phenyl)-3-trifluoromethyl-pyrazine-2-carboxylic acid ((1R,2R)-2-hydroxy-cyclohexyl)-amide수율 82.9%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

To a yellow suspension of 1.50 g 5-bromo-6-(4-chloro-phenyl)-3-trifluoromethyl-pyrazine-2-carboxylic acid in 11 ml dichloromethane was added drop wise 0.608 g 1-chloro-N,N, 2-trimethylpropenylamine and the resulting the yellow solution was stirred at room temperature for 30 min. The resulting orange solution was added dropwise to a cooled (ice bath) solution of 0.522 g (1R,2R)-2-amino-cyclohexanol and 0.7868 g ethyldiisopropylamine in 10 ml ethyl acetate. This red solution was stirred at room temperature for 90 min. To the red solution was added 30 ml 10% aqueous citric acid solution. The layers were separated and the organic layer was purified by chromatography on silica gel with a gradient of heptane: ethyl acetate=1:1 to ethyl acetate to yield 1.56 g of the title compound as yellow crystals. MS (M−H) at 479.0 and 476.0.

후처리

  1. additionThe resulting orange solution was added dropwise to
  2. stirringThis red solution was stirred at room temperature for 90 min
  3. customThe layers were separated
  4. customthe organic layer was purified by chromatography on silica gel with a gradient of heptane

출처 및 근거

ORD 기록
ord-ac4c025389014761ae8146eccb6d4fd4
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08088920B2

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