1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinecarbothioamide → 1-[4-[4-[(5R)-4,5-dihydro-5-phenyl-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone

HRID 1528553ノート

反応式

HRID 1528553 の反応式
[CH3:1][C:2]1[N:6]([CH2:7][C:8]([N:10]2[CH2:15][CH2:14][CH:13]([C:16](=[S:18])[NH2:17])[CH2:12][CH2:11]2)=[O:9])[N:5]=[C:4]([C:19]([F:22])([F:21])[F:20])[CH:3]=1.Br[CH2:24][C:25]([C:27]1[CH2:31][C@H:30]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[O:29][N:28]=1)=O>C(O)C.O>[C:32]1([C@@H:30]2[O:29][N:28]=[C:27]([C:25]3[N:17]=[C:16]([CH:13]4[CH2:14][CH2:15][N:10]([C:8](=[O:9])[CH2:7][N:6]5[C:2]([CH3:1])=[CH:3][C:4]([C:19]([F:22])([F:20])[F:21])=[N:5]5)[CH2:11][CH2:12]4)[S:18][CH:24]=3)[CH2:31]2)[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1

参加物

5

反応物 2

HCID 580788971-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinecarbothioamide2 回HCID 866312472-bromo-1-[(5R)-4,5-dihydro-5-phenyl-3-isoxazolyl]ethanone2 回

生成物 1

HCID 666012751-[4-[4-[(5R)-4,5-dihydro-5-phenyl-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 962Water溶媒

反応条件

温度
50 °C

実験手順

A mixture of 1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidine-carbothioamide (i.e. the product of Example 8, Step C) (1.7 g, 5.0 mmol) and 2-bromo-1-[(5R)-4,5-dihydro-5-phenyl-3-isoxazolyl]ethanone (i.e. the product of Example 12, Step E or E1) (1.35 g, 5 mmol) in ethanol (15 mL) was heated at 50° C. for 30 minutes. The reaction mixture was diluted with water and extracted with dichloromethane. The extract was washed with brine, dried (MgSO4), and concentrated under reduced pressure to give the title product, a compound of the present invention, as a pale-yellow gum. High performance liquid chromatography (HPLC) analysis showed that the title product was about 95% pure and contained the (R)-enantiomer in about 98% enantiomeric excess.

後処理

  1. extractionextracted with dichloromethane
  2. washThe extract was washed with brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-9bf95581a8414df9aedba1f245cc1b55
出典データセット
uspto-grants-2015_07
特許番号
US09090604B2

反応ノート

読み込み中…