2-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetic acid → 1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]tetrahydro-1(2H)-pyridazinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone

HRID 75174

反応式

HRID 75174 の反応式
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[CH:9]1[O:13][N:12]=[C:11]([C:14]2[N:15]=[C:16]([CH:19]3[CH2:24][CH2:23][NH:22][NH:21][CH2:20]3)[S:17][CH:18]=2)[CH2:10]1.[CH3:25][C:26]1[N:30]([CH2:31][C:32](O)=[O:33])[N:29]=[C:28]([C:35]([F:38])([F:37])[F:36])[CH:27]=1>ClCCl>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[CH:9]1[O:13][N:12]=[C:11]([C:14]2[N:15]=[C:16]([CH:19]3[CH2:24][CH2:23][N:22]([C:32](=[O:33])[CH2:31][N:30]4[C:26]([CH3:25])=[CH:27][C:28]([C:35]([F:38])([F:37])[F:36])=[N:29]4)[NH:21][CH2:20]3)[S:17][CH:18]=2)[CH2:10]1

参加物

4

反応物 2

HCID 5961182-(5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetic acidHCID 673224374-[4-[5-(2,6-Difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]hexahydropyridazine2 回

生成物 1

HCID 866744671-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]tetrahydro-1(2H)-pyridazinyl]-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

A mixture of 4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]hexahydropyridazine (i.e. the product of Step H) (0.29 g, 0.83 mmol), 5-methyl-3-(trifluoromethyl)-1H-pyrazole-1-acetic acid (0.19 g, 0.91 mmol) and N,N-dicyclohexylcarbodiimide (0.19 g, 0.91 mmol) in dichloromethane (5 mL) was stirred at room temperature for 48 h. More dichloromethane was added to the reaction mixture, the mixture was filtered, washing thoroughly with dichloromethane. The filtrate was concentrated under reduced pressure and loaded onto a chromatotron plate (4 mm). The plate was eluted with dichloromethane, followed by a gradient of 0.5% to 2% methanol in dichloromethane. Fractions containing product material were further purified by HPLC using an Alltima C18 column (250×22 mm), monitored at wavelength 225 nm and eluted with 60% methanol and 0.1% 2,2,2-trifluoroacetic acid in water to provide the title compound (69 mg), a compound of the present invention.

後処理

  1. filtrationthe mixture was filtered
  2. washwashing thoroughly with dichloromethane
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. washThe plate was eluted with dichloromethane
  5. additionFractions containing product material
  6. customwere further purified by HPLC
  7. washeluted with 60% methanol and 0.1% 2,2,2-trifluoroacetic acid in water

出典と根拠

ORDレコード
ord-0c4c8040853043be8315d94e4fb8bec8
出典データセット
uspto-grants-2014_09
特許番号
US08835427B2

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