Dichloromethane → (R)-2-(2-(6-((R)-1-((S)-3-aminopyrrolidin-1-yl)-2,2,2-trifluoroethyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)propan-1-ol dihydrochloride

HRID 339010노트

반응식

HRID 339010 반응식
[Si]([O:8][CH2:9][C@H:10]([O:12][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[N:21]=[C:20]([C:23]1[N:27]3[CH:28]=[C:29]([C@@H:32]([N:37]4[CH2:41][CH2:40][C@H:39]([NH:42]C(=O)OC(C)(C)C)[CH2:38]4)[C:33]([F:36])([F:35])[F:34])[CH:30]=[CH:31][C:26]3=[N:25][N:24]=1)[CH:19]=[CH:18]2)[CH3:11])(C(C)(C)C)(C)C.FC(F)(F)C(O)=O.[Cl:57]CCl>>[ClH:57].[ClH:57].[NH2:42][C@H:39]1[CH2:40][CH2:41][N:37]([C@H:32]([C:29]2[CH:30]=[CH:31][C:26]3[N:27]([C:23]([C:20]4[CH:19]=[CH:18][C:17]5[C:22](=[C:13]([O:12][C@H:10]([CH3:11])[CH2:9][OH:8])[CH:14]=[CH:15][CH:16]=5)[N:21]=4)=[N:24][N:25]=3)[CH:28]=2)[C:33]([F:35])([F:36])[F:34])[CH2:38]1

참가 물질

4

반응물 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 86707510tert-butyl (S)-1-((R)-1-(3-(8-((R)-1-(tert-butyldimethylsilyloxy)propan-2-yloxy)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-2,2,2-trifluoroethyl)pyrrolidin-3-ylcarbamate

생성물 1

HCID 86707511(R)-2-(2-(6-((R)-1-((S)-3-aminopyrrolidin-1-yl)-2,2,2-trifluoroethyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)propan-1-ol dihydrochloride수율 73%

실험 절차

To a solution of tert-butyl (S)-1-((R)-1-(3-(8-((R)-1-(tert-butyldimethylsilyloxy)propan-2-yloxy)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-2,2,2-trifluoroethyl)pyrrolidin-3-ylcarbamate (0.29 g, 0.41 mmol) in dichloromethane (1 mL) was added trifluoroacetic acid (2 mL) was stirred at ambient temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure. The residue was purified by reverse phase chromatography on C18 (0-80% acetonitrile/water). The material isolated after purification was dissolved in methanol (0.5 mL) and added dropwise to hydrochloric acid (2M in diethyl ether; 5 mL). The resulting salt was collected by vacuum filtration to provide the title compound (0.17 g, 73%). LCMS APCI (+) m/z 487 (M+H).

후처리

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customThe residue was purified by reverse phase chromatography on C18 (0-80% acetonitrile/water)
  3. customThe material isolated
  4. customafter purification
  5. dissolutionwas dissolved in methanol (0.5 mL)
  6. additionadded dropwise to hydrochloric acid (2M in diethyl ether; 5 mL)
  7. filtrationThe resulting salt was collected by vacuum filtration

출처 및 근거

ORD 기록
ord-e9db7bd0db474924bf2e21330c325344
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08889704B2

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