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 339010Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 339010
[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

Komponenten

4

Edukt 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

Produkt 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 dihydrochlorideAusbeute 73 %

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-e9db7bd0db474924bf2e21330c325344
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08889704B2

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