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

HRID 1475671ノート

反応式

HRID 1475671 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([CH:9]([O:20][CH3:21])[C:10]2([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:12][CH2:11]2)[CH:5]=[CH:6][C:7]=1[Cl:8].[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.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]([CH:9]([O:20][CH3:21])[C:10]2([C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])[CH2:11][CH2:12]2)=[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 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 acid2 回HCID 68170329(+/-)-tert-Butyl 1-[(3-amino-4-chlorophenyl)(methoxy)methyl]cyclopropanecarboxylate

生成物 1

HCID 68006868tert-butyl 1-[(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)(methoxy)methyl]cyclopropanecarboxylate

試薬・触媒・溶媒 3

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

実験手順

200 mg (0.641 mmol) of (+/−)-tert-butyl 1-[(3-amino-4-chlorophenyl)(methoxy)methyl]cyclopropanecarboxylate and 188 mg (0.706 mmol) of (+)-(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoic acid were dissolved in 2.3 ml of DMF and 0.7 ml of pyridine, and 293 mg (0.770 mmol) of HATU were added at RT. The reaction mixture was stirred at RT overnight. Another 0.6 eq. of (+)-(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoic acid was then added, and the reaction mixture was stirred at 45° C. for 14 h. 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 168 mg of the target compound (39.9% of theory).

後処理

  1. stirringthe reaction mixture was stirred at 45° C. for 14 h
  2. temperatureAfter cooling
  3. washthe solution was washed with 1 N hydrochloric acid and saturated sodium chloride solution
  4. dry with materialdried over magnesium sulphate
  5. concentrationconcentrated under reduced pressure
  6. 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-349e76b90c52415c97e34f3abd36a3db
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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