Acetic Acid → N-((1S,3S,4R)-3-(3-(4-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)propylamino)-4-ethylcyclopentyl)cyclopropanesulfonamide

HRID 1969875노트

반응식

HRID 1969875 반응식
[Cl:1][C:2]1[C:7]([CH2:8][CH2:9][CH:10]=O)=[CH:6][N:5]=[C:4]2[N:12]([S:15]([C:18]3[CH:24]=[CH:23][C:21]([CH3:22])=[CH:20][CH:19]=3)(=[O:17])=[O:16])[CH:13]=[CH:14][C:3]=12.[CH2:25]([C@H:27]1[C@@H:31]([N:32]=C=O)[CH2:30][C@@H:29]([NH:35][S:36]([CH:39]2[CH2:41][CH2:40]2)(=[O:38])=[O:37])[CH2:28]1)[CH3:26].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl.C(Cl)Cl>[Cl:1][C:2]1[C:7]([CH2:8][CH2:9][CH2:10][NH:32][C@@H:31]2[C@H:27]([CH2:25][CH3:26])[CH2:28][C@H:29]([NH:35][S:36]([CH:39]3[CH2:41][CH2:40]3)(=[O:38])=[O:37])[CH2:30]2)=[CH:6][N:5]=[C:4]2[N:12]([S:15]([C:18]3[CH:24]=[CH:23][C:21]([CH3:22])=[CH:20][CH:19]=3)(=[O:17])=[O:16])[CH:13]=[CH:14][C:3]=12

참가 물질

8

반응물 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 585575753-(4-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)propanalHCID 58557883N-((1S,3R,4S)-3-ethyl-4-isocyanatocyclopentyl)cyclopropanesulfonamide

생성물 1

HCID 58557549N-((1S,3S,4R)-3-(3-(4-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)propylamino)-4-ethylcyclopentyl)cyclopropanesulfonamide수율 55%

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매HCID 6344Dichloromethane용매

실험 절차

To a mixture of 3-(4-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)propanal (0.420 g, 1.04 mmol) and N-((1S,3S,4R)-3-amino-4-ethylcyclopentyl)cyclopropanesulfonamide (0.290 g, 1.25 mmol, prepared using OOO from Example #23 step E with NaOH) in DCE (4.00 mL) was added glacial acetic acid (0.089 mL, 1.6 mmol). The reaction mixture stirred for about 15 min at ambient temperature and sodium triacetoxyborohydride (0.331 g, 1.56 mmol) was added. The reaction was left stirring at ambient temperature for about 72 h. Saturated aqueous NaHCO3 (about 5 mL) was slowly added followed by DCM (5 mL). The layers were separated and the aqueous phase was extracted with DCM (2×5 mL). The combined organics were dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The remaining yellow oil was purified by silica gel chromatography eluting with a gradient of 0-50% EtOAc in heptane to give N-((1S,3S,4R)-3-(3-(4-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-5-yl)propylamino)-4-ethylcyclopentyl)cyclo-propanesulfonamide (0.330 g, 55%) as a white foam: LC/MS (Table 1, Method b) Rt=2.10 min; MS m/z: 579 (M+H)+.

후처리

  1. waitThe reaction was left
  2. stirringstirring at ambient temperature for about 72 h
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with DCM (2×5 mL)
  5. dry with materialThe combined organics were dried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe remaining yellow oil was purified by silica gel chromatography
  9. washeluting with a gradient of 0-50% EtOAc in heptane

출처 및 근거

ORD 기록
ord-76f963c714d94da4a8cda69f8d8167f4
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08426411B2

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