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

반응식

HRID 75174 반응식
[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

참가 물질

4

반응물 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]hexahydropyridazine2회

생성물 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

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-0c4c8040853043be8315d94e4fb8bec8
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08835427B2

연결된 노트

불러오는 중…