Water → 2-(3-Chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid [4-chloro-2-methyl-6-(3-methyl-thietan-3-ylcarbamoyl)-phenyl]-amide

HRID 660124노트

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HRID 660124 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([CH3:29])[C:5]2[N:10]=[C:9]([C:11]3[N:15]([C:16]4[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][N:17]=4)[N:14]=[C:13]([C:23]([F:26])([F:25])[F:24])[CH:12]=3)[O:8][C:7](=[O:27])[C:6]=2[CH:28]=1.[NH2:30][C:31]1([CH3:35])[CH2:34][S:33][CH2:32]1.O>O1CCCC1>[Cl:1][C:2]1[CH:28]=[C:6]([C:7](=[O:27])[NH:30][C:31]2([CH3:35])[CH2:34][S:33][CH2:32]2)[C:5]([NH:10][C:9]([C:11]2[N:15]([C:16]3[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][N:17]=3)[N:14]=[C:13]([C:23]([F:26])([F:25])[F:24])[CH:12]=2)=[O:8])=[C:4]([CH3:29])[CH:3]=1

참가 물질

5

반응물 3

HCID 962WaterHCID 231503516-chloro-2-[2-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazol-3-yl]-8-methylbenzo[d][1,3]oxazin-4-oneHCID 552816773-Methylthietan-3-amine2회

생성물 1

HCID 593935852-(3-Chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid [4-chloro-2-methyl-6-(3-methyl-thietan-3-ylcarbamoyl)-phenyl]-amide수율 40%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
50 °C

실험 절차

To a solution of 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazin-4-one (1.13 g, 2.56 mmol) (prepared according to WO 02/48115, example 2D) in tetrahydrofuran (15 ml) is added 3-amino-3-methyl-thietane (the product of step 3) (0.66 g, 6.40 mmol), and the mixture is heated for 48 hours at 50° C., then to reflux for 12 hours. The cooled reaction mixture is poured into water, extracted with ethyl acetate, the combined organic layers washed with water and brine, dried (Na2SO4), filtered, and concentrated. The crude product is purified by flash chromatography (ethyl acetate/hexane 1:2) to afford 560 mg (40%) of the title compound as a white solid, m.p. 238-241° C.

후처리

  1. temperatureto reflux for 12 hours
  2. customThe cooled reaction mixture
  3. extractionextracted with ethyl acetate
  4. washthe combined organic layers washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product is purified by flash chromatography (ethyl acetate/hexane 1:2)

출처 및 근거

ORD 기록
ord-8c1ca71d6ef74173a4af3f5c8b120ab3
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08084474B2

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