Sodium Bicarbonate → [(r)-3-(5,6-Difluoro-benzothiazol-2-ylamino)-pyrrolidin-1-yl]-(5-methyl-2-trifluoromethyl-phenyl)-methanone

HRID 598522노트

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HRID 598522 반응식
[F:1][C:2]1[C:3]([F:14])=[CH:4][C:5]2[S:9][C:8](S(C)=O)=[N:7][C:6]=2[CH:13]=1.[NH2:15][C@@H:16]1[CH2:20][CH2:19][N:18]([C:21]([C:23]2[CH:28]=[C:27]([CH3:29])[CH:26]=[CH:25][C:24]=2[C:30]([F:33])([F:32])[F:31])=[O:22])[CH2:17]1.C([O-])(O)=O.[Na+]>CS(C)=O.O>[F:1][C:2]1[C:3]([F:14])=[CH:4][C:5]2[S:9][C:8]([NH:15][C@@H:16]3[CH2:20][CH2:19][N:18]([C:21]([C:23]4[CH:28]=[C:27]([CH3:29])[CH:26]=[CH:25][C:24]=4[C:30]([F:33])([F:31])[F:32])=[O:22])[CH2:17]3)=[N:7][C:6]=2[CH:13]=1

참가 물질

6

반응물 3

HCID 516892Sodium BicarbonateHCID 577489385,6-Difluoro-2-(methylsulfinyl)benzo[d]thiazoleHCID 57748952((R)-3-Amino-pyrrolidin-1-yl)-(5-methyl-2-trifluoromethyl-phenyl)-methanone2회

생성물 1

HCID 42641617[(r)-3-(5,6-Difluoro-benzothiazol-2-ylamino)-pyrrolidin-1-yl]-(5-methyl-2-trifluoromethyl-phenyl)-methanone수율 47.6%

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 962Water용매

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온도
100 °C

실험 절차

A mixture of 30 mg (0.129 mmol) rac-5,6-difluoro-2-methanesulfinyl-benzothiazole and 70.3 mg (0.258 mmol) ((R)-3-Amino-pyrrolidin-1-yl)-(5-methyl-2-trifluoromethyl-phenyl)-methanone (intermediate 13) in 540 μL dimethyl sulfoxide was heated in a 100° C. oil-bath for 4 h. The solution was cooled to room temperature, diluted with water and basified with a saturated NaHCO3 solution. The mixture was stirred for 1 h. The solid was filtered, washed with water and dissolved in dichloromethane. The solution was dried over Na2SO4, filtered and concentrated in vacuo. The crude compound was purified with flash column chromatography on silica eluting with a gradient formed from n-heptane and ethyl acetate to provide 27 mg (47.6%) of the title compound as a white solid. MS(m/e): 442.2 (M+H+).

후처리

  1. temperatureThe solution was cooled to room temperature
  2. filtrationThe solid was filtered
  3. washwashed with water
  4. dissolutiondissolved in dichloromethane
  5. dry with materialThe solution was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude compound was purified with flash column chromatography on silica eluting with a gradient
  9. customformed from n-heptane and ethyl acetate

출처 및 근거

ORD 기록
ord-cfd520eb60e74003b6fef6c9257ca90f
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07897627B2

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