Isopropylamine → tert-butyl (3S)-1-(2,2,2-trifluoro-1-(3-(7-(isopropylcarbamoyl)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-ylcarbamate

HRID 338863Notes

Reaction equation

HRID 338863 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][CH2:12][N:11]([CH:14]([C:19]2[CH:20]=[CH:21][C:22]3[N:23]([C:25]([C:28]4[CH:37]=[CH:36][C:35]5[C:30](=[CH:31][C:32]([C:38]([OH:40])=O)=[CH:33][CH:34]=5)[N:29]=4)=[N:26][N:27]=3)[CH:24]=2)[C:15]([F:18])([F:17])[F:16])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=[N:56][C:51]2[CH:52]=CC=N[C:50]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CC(N)C.CCN(C(C)C)C(C)C>CN(C=O)C>[F:18][C:15]([F:17])([F:16])[CH:14]([N:11]1[CH2:12][CH2:13][C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:10]1)[C:19]1[CH:20]=[CH:21][C:22]2[N:23]([C:25]([C:28]3[CH:37]=[CH:36][C:35]4[C:30](=[CH:31][C:32]([C:38](=[O:40])[NH:56][CH:51]([CH3:52])[CH3:50])=[CH:33][CH:34]=4)[N:29]=3)=[N:26][N:27]=2)[CH:24]=1

Participants

6

Reactant 4

HCID 6363IsopropylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 709845972-(6-(1-((S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl)-2,2,2-trifluoroethyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinoline-7-carboxylic acid

Product 1

HCID 86707421tert-butyl (3S)-1-(2,2,2-trifluoro-1-(3-(7-(isopropylcarbamoyl)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-ylcarbamateYield 28.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(6-(1-((S)-3-(tert-butoxycarbonylamino)pyrrolidin-1-yl)-2,2,2-trifluoroethyl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinoline-7-carboxylic acid (0.075 g, 0.135 mmol), HATU (0.062 g, 0.16 mmol) and propan-2-amine (0.057 ml, 0.67 mmol) in DMF (1 mL) was added DIEA (0.047 mL, 0.27 mmol) and the reaction mixture was stirred at ambient temperature for 4 hours. The reaction mixture was purified directly by C-18 reverse phase flash chromatography (Biotage SP4 unit, C-18 25M column, 0-90% CH3CN/water gradient; 30 CV)) to give tert-butyl (3S)-1-(2,2,2-trifluoro-1-(3-(7-(isopropylcarbamoyl)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)ethyl)pyrrolidin-3-ylcarbamate (0.023 g, 28.6%) as a solid.

Workup

  1. customThe reaction mixture was purified directly by C-18 reverse phase flash chromatography (Biotage SP4 unit

Sources & evidence

ORD record
ord-be7edfec7e9c4b5783ea2dc987acd9a3
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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