Pyridine → tert-butyl 1-(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}benzyl)-2,2-difluorocyclopropanecarboxylate

HRID 1475665노트

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HRID 1475665 반응식
[NH2:1][C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][C:20]=1[Cl:21])[CH2:5][C:6]1([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:8][C:7]1([F:10])[F:9].[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([C@H:29]([C@@H:33]([CH3:38])[C:34]([F:37])([F:36])[F:35])[C:30](O)=[O:31])=[CH:25][CH:24]=1.N1C=CC=CC=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C>[Cl:21][C:20]1[CH:19]=[CH:18][C:4]([CH2:5][C:6]2([C:11]([O:13][C:14]([CH3:17])([CH3:15])[CH3:16])=[O:12])[CH2:8][C:7]2([F:10])[F:9])=[CH:3][C:2]=1[NH:1][C:30](=[O:31])[C@H:29]([C:26]1[CH:25]=[CH:24][C:23]([Cl:22])=[CH:28][CH:27]=1)[C@@H:33]([CH3:38])[C:34]([F:35])([F:36])[F:37]

참가 물질

7

반응물 4

HCID 1049PyridineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58288396(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoic acidHCID 68170287tert-Butyl 1-(3-amino-4-chlorobenzyl)-2,2-difluorocyclopropanecarboxylate

생성물 1

HCID 86667526tert-butyl 1-(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}benzyl)-2,2-difluorocyclopropanecarboxylate

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

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온도
40 °C

실험 절차

1.15 g (3.62 mmol) of (+/−)-tert-butyl 1-(3-amino-4-chlorobenzyl)-2,2-difluorocyclopropane-carboxylate were dissolved in 5 ml of DMF, and 1.49 g (5.43 mmol) of (+)-(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoic acid, 2.5 ml of pyridine and 1.79 g (4.71 mmol) of HATU were added at RT. The reaction mixture was then stirred at 40° C. overnight. After cooling, the mixture was diluted with ethyl acetate and the solution was washed with 1 N hydrochloric acid and saturated sodium chloride solution, dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 30:1). This gave 1.82 g of the title compound (88.8% of theory).

후처리

  1. temperatureAfter cooling
  2. washthe solution was washed with 1 N hydrochloric acid and saturated sodium chloride solution
  3. dry with materialdried over magnesium sulphate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 30:1)

출처 및 근거

ORD 기록
ord-25ea0ee45fbf4ad587603ba6bbac5882
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09018258B2

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