Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → Ethyl(2R)-3-(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}-phenyl)-2-methylpropanoate

HRID 1476086ノート

反応式

HRID 1476086 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([CH2:9][C@@H:10]([CH3:16])[C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8].[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([C@H:24]([C@@H:28]([CH3:33])[C:29]([F:32])([F:31])[F:30])[C:25](O)=[O:26])=[CH:20][CH:19]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.N1C=CC=CC=1.C(OCC)(=O)C>[Cl:8][C:7]1[CH:6]=[CH:5][C:4]([CH2:9][C@@H:10]([CH3:16])[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:3][C:2]=1[NH:1][C:25](=[O:26])[C@H:24]([C:21]1[CH:20]=[CH:19][C:18]([Cl:17])=[CH:23][CH:22]=1)[C@@H:28]([CH3:33])[C:29]([F:30])([F:31])[F:32]

参加物

7

反応物 3

HCID 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 58288409ethyl(-)-(2R)-3-(3-amino-4-chlorophenyl)-2-methylpropanoate

生成物 1

HCID 58288446Ethyl(2R)-3-(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}-phenyl)-2-methylpropanoate

試薬・触媒・溶媒 3

HCID 1049Pyridine溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

500 mg (2.07 mmol) of ethyl (−)-(2R)-3-(3-amino-4-chlorophenyl)-2-methylpropanoate and 607 mg (2.28 mmol) of (2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoic acid were dissolved in a mixture of 2.0 ml of DMF and 1.0 ml of pyridine, and 1022 mg (2.69 mmol) of HATU were added at room temperature. The reaction mixture was stirred at RT overnight. The mixture was diluted with ethyl acetate, and the solution was washed successively with 1 N hydrochloric acid, water, saturated sodium bicarbonate solution and saturated sodium chloride solution. The organic phase was dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 40:1). This gave 998 mg (98.4% of theory) of the target compound.

後処理

  1. additionwere added at room temperature
  2. washthe solution was washed successively with 1 N hydrochloric acid, water, saturated sodium bicarbonate solution and saturated sodium chloride solution
  3. dry with materialThe organic phase was dried over magnesium sulphate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 40:1)

出典と根拠

ORDレコード
ord-acc784070cd5428998b16114e3fa199e
出典データセット
uspto-grants-2015_04
特許番号
US09018414B2

反応ノート

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