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(1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine hydrochloride → 1-((1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3-(4-(1,3-dihydroxypropan-2-yl)-3-fluorophenyl)urea

HRID 1842962
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HRID 1842962 반응식
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([N:9]2[C:13]([CH2:14][NH2:15])=[CH:12][C:11]([C:16]([F:19])([F:18])[F:17])=[N:10]2)[CH:6]=[CH:7][CH:8]=1.[OH:20][CH2:21][CH:22]([C:25]1[CH:30]=[CH:29][C:28]([NH:31][C:32](=O)[O:33]C2C=CC=CC=2)=[CH:27][C:26]=1[F:41])[CH2:23][OH:24]>CN(C=O)C.O>[Cl:2][C:3]1[CH:4]=[C:5]([N:9]2[C:13]([CH2:14][NH:15][C:32]([NH:31][C:28]3[CH:29]=[CH:30][C:25]([CH:22]([CH2:21][OH:20])[CH2:23][OH:24])=[C:26]([F:41])[CH:27]=3)=[O:33])=[CH:12][C:11]([C:16]([F:17])([F:18])[F:19])=[N:10]2)[CH:6]=[CH:7][CH:8]=1
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참가 물질

5

반응물 2

HCID 70816151(1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine hydrochlorideHCID 86672159Phenyl 4-(1,3-dihydroxypropan-2-yl)-3-fluorophenylcarbamate

생성물 1

HCID 708163971-((1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3-(4-(1,3-dihydroxypropan-2-yl)-3-fluorophenyl)urea수율 36%

시약·촉매·용매 2

HCID 962Water용매
HCID 6228
Dimethylformamide
용매

실험 절차

To a stirred solution of (1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methanamine hydrochloride (153 mg, 0.4918 mmol, 1.0 eq) in DMF (5 mL) was added TEA (0.205 mL, 1.4754 mmol, 3.0 eq) followed by phenyl 4-(1,3-dihydroxypropan-2-yl)-3-fluorophenylcarbamate (150 mg, 0.4918 mmol, 1.0 eq) at RT and the mixture stirred for 16 h. The reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (15 mL). The organic layer was washed with water (10 mL) and brine (5 mL), dried over anhydrous Na2SO4, and evaporated under vacuum. The crude product was purified by neutral alumina column chromatography using MeOH/CHCl3 (1:19) as eluent to get 1-((1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-3-(4-(1,3-dihydroxypropan-2-yl)-3-fluorophenyl)urea (85.5 mg; 36%) as off white solid; TLC system: MeOH/CHCl3 (1:9); Rf: 0.5).

후처리

  1. extractionextracted with ethyl acetate (15 mL)
  2. washThe organic layer was washed with water (10 mL) and brine (5 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. customevaporated under vacuum
  5. customThe crude product was purified by neutral alumina column chromatography

출처 및 근거

ORD 기록
ord-f838c0ba47ab487d9e51d939891470f2
출처 데이터셋
uspto-grants-2015_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08946204B2

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