Lithium Hydroxide → tert-butyl (S)-1-((R)-2,2,2-trifluoro-1-(3-(6-fluoro-7-(2-hydroxyethoxy)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-ylcarbamate

HRID 338936Notes

Reaction equation

HRID 338936 reaction equation
C([O:4][CH2:5][CH2:6][O:7][C:8]1[CH:17]=[C:16]2[C:11]([CH:12]=[CH:13][C:14]([C:18]3[N:22]4[CH:23]=[C:24]([C@@H:27]([N:32]5[CH2:36][CH2:35][C@H:34]([NH:37][C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:33]5)[C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:26][C:21]4=[N:20][N:19]=3)=[N:15]2)=[CH:10][C:9]=1[F:45])(=O)C.[Li+].[OH-]>CO>[F:31][C:28]([F:29])([F:30])[C@H:27]([N:32]1[CH2:36][CH2:35][C@H:34]([NH:37][C:38](=[O:39])[O:40][C:41]([CH3:44])([CH3:42])[CH3:43])[CH2:33]1)[C:24]1[CH:25]=[CH:26][C:21]2[N:22]([C:18]([C:14]3[CH:13]=[CH:12][C:11]4[C:16](=[CH:17][C:8]([O:7][CH2:6][CH2:5][OH:4])=[C:9]([F:45])[CH:10]=4)[N:15]=3)=[N:19][N:20]=2)[CH:23]=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 709830682-(2-(6-((R)-1-((S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl)-2,2,2-trifluoroethyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-6-fluoroquinolin-7-yloxy)ethyl acetate

Product 1

HCID 86707460tert-butyl (S)-1-((R)-2,2,2-trifluoro-1-(3-(6-fluoro-7-(2-hydroxyethoxy)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-ylcarbamateYield 90%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To 2-(2-(6-((R)-1-((S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl)-2,2,2-trifluoroethyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-6-fluoro quinolin-7-yloxy)ethyl acetate (250 mg, 0.395 mmol) (Example 122, Step A) in MeOH (5 mL) was added 2N LiOH (1 mL) and the reaction was stirred at ambient temperature for 1 hour. The reaction was concentrated and the residue purified by reverse phase chromatography (SP4, 12M, eluting with a gradient of water/ACN 100:0 to 0:100, 25 column volumes) to yield tert-butyl (S)-1-((R)-2,2,2-trifluoro-1-(3-(6-fluoro-7-(2-hydroxyethoxy)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-ylcarbamate (210 mg, 90.0% yield) as a white solid.

Workup

  1. concentrationThe reaction was concentrated
  2. customthe residue purified by reverse phase chromatography (SP4, 12M
  3. washeluting with a gradient of water/ACN 100:0 to 0:100, 25 column volumes)

Sources & evidence

ORD record
ord-9d7e793ad6be4c509124cd72c4e70ce5
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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