5-((2R,4S)-4-carbamoyl-2-(3-fluorophenyl)pyrrolidin-1-yl)-N,N-bis(4-methoxybenzyl)pyrazolo[1,5-a]pyridine-3-carboxamide → 5-((2R,4S)-4-carbamoyl-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxamide

HRID 513057Notes

Reaction equation

HRID 513057 reaction equation
[C:1]([C@@H:4]1[CH2:8][N:7]([C:9]2[CH:14]=[CH:13][N:12]3[N:15]=[CH:16][C:17]([C:18]([N:20](CC4C=CC(OC)=CC=4)CC4C=CC(OC)=CC=4)=[O:19])=[C:11]3[CH:10]=2)[C@@H:6]([C:39]2[CH:44]=[CH:43][CH:42]=[C:41]([F:45])[CH:40]=2)[CH2:5]1)(=[O:3])[NH2:2]>C(O)(C(F)(F)F)=O.CS(C)=O>[C:1]([C@@H:4]1[CH2:8][N:7]([C:9]2[CH:14]=[CH:13][N:12]3[N:15]=[CH:16][C:17]([C:18]([NH2:20])=[O:19])=[C:11]3[CH:10]=2)[C@@H:6]([C:39]2[CH:44]=[CH:43][CH:42]=[C:41]([F:45])[CH:40]=2)[CH2:5]1)(=[O:3])[NH2:2]

Participants

4

Reactant 1

HCID 682821825-((2R,4S)-4-carbamoyl-2-(3-fluorophenyl)pyrrolidin-1-yl)-N,N-bis(4-methoxybenzyl)pyrazolo[1,5-a]pyridine-3-carboxamide

Product 1

HCID 601718265-((2R,4S)-4-carbamoyl-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 5-((2R,4S)-4-carbamoyl-2-(3-fluorophenyl)pyrrolidin-1-yl)-N,N-bis(4-methoxybenzyl)pyrazolo[1,5-a]pyridine-3-carboxamide (I-54) (10 mg, 0.016 mmol) in TFA (0.5 mL) was heated to 60° C. for 2 hours. The reaction was reduced to dryness and the crude material was taken up in DMSO and purified by preparative LCMS and lyophilized to give 5-((2R,4S)-4-carbamoyl-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxamide (X-26). 1H NMR (400 MHz, DMSO) δ 8.38 (d, J=7.7 Hz, 1 H), 8.26 (s, 1 H), 7.53 (s, 1 H), 7.44-7.31 (m, 1H), 7.15-7.01 (m, 2 H), 6.96 (s, 1 H), 6.31 (d, J=7.1 Hz, 1 H), 5.13 (d, J=8.0 Hz, 1 H), 3.98-3.85 (m, 1 H), 3.65-3.54 (m, 1 H), 3.20-3.07 (m, 1 H), 2.60-2.52 (m, 1 H), 2.08 (dd, J=6.9, 12.0 Hz, 1 H). MS m/z 368.1 (M+1)+.

Workup

  1. custompurified by preparative LCMS

Sources & evidence

ORD record
ord-7507d4a844d8498f9d1407fe9593381b
Source dataset
uspto-grants-2015_08
Patent number
US09102671B2

Reaction notes

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