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

HRID 660129노트

반응식

HRID 660129 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.C(N(CC)CC)C.Br.[S:38]1[CH2:41][CH:40]([NH2:42])[CH2:39]1.O>O1CCCC1>[Cl:1][C:2]1[CH:28]=[C:6]([C:7](=[O:27])[NH:42][CH:40]2[CH2:41][S:38][CH2:39]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:24])([F:25])[F:26])[CH:12]=2)=[O:8])=[C:4]([CH3:29])[CH:3]=1

참가 물질

6

반응물 4

HCID 962WaterHCID 8471TriethylamineHCID 231503516-chloro-2-[2-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazol-3-yl]-8-methylbenzo[d][1,3]oxazin-4-oneHCID 53346555Thietan-3-amine hydrobromide2회

생성물 1

HCID 593935962-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazole-3-carboxylic acid [4-chloro-2-methyl-6-(thietan-3-ylcarbamoyl)-phenyl]-amide수율 41%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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 (500 mg, 1.13 mmol) [prepared according to WO 02/48115, example 2D] in tetrahydrofuran (10 ml) is added triethylamine (0.4 ml, 2.87 mmol) and 3-thietanamine hydrobromide salt [the product of step 2] (250 mg, 1.47 mmol), and the mixture is heated to reflux overnight. 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 250 mg (41%) of the title compound as a white solid.

후처리

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

출처 및 근거

ORD 기록
ord-86eb829963ad4b1396532726bd6e2ca5
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08084474B2

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