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

HRID 1475665ノート

反応式

HRID 1475665 の反応式
[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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
40 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-25ea0ee45fbf4ad587603ba6bbac5882
出典データセット
uspto-grants-2015_04
特許番号
US09018258B2

反応ノート

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