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 339010Notes

Reaction equation

HRID 339010 reaction equation
[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

Participants

4

Reactant 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

Product 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 dihydrochlorideYield 73%

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-e9db7bd0db474924bf2e21330c325344
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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