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

HRID 513055Notes

Reaction equation

HRID 513055 reaction equation
[C:1]([C@@H:3]1[CH2:7][N:6]([C:8]2[CH:13]=[CH:12][N:11]3[N:14]=[CH:15][C:16]([C:17]([N:19](CC4C=CC(OC)=CC=4)CC4C=CC(OC)=CC=4)=[O:18])=[C:10]3[CH:9]=2)[C@@H:5]([C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([F:44])[CH:39]=2)[CH2:4]1)#[N:2]>C(O)(C(F)(F)F)=O.CS(C)=O>[C:1]([C@@H:3]1[CH2:7][N:6]([C:8]2[CH:13]=[CH:12][N:11]3[N:14]=[CH:15][C:16]([C:17]([NH2:19])=[O:18])=[C:10]3[CH:9]=2)[C@@H:5]([C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([F:44])[CH:39]=2)[CH2:4]1)#[N:2]

Participants

4

Reactant 1

HCID 682824635-((2R,4S)-4-cyano-2-(3-fluorophenyl)pyrrolidin-1-yl)-N,N-bis(4-methoxybenzyl)pyrazolo[1,5-a]pyridine-3-carboxamide

Product 1

HCID 601718255-((2R,4S)-4-cyano-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-cyano-2-(3-fluorophenyl)pyrrolidin-1-yl)-N,N-bis(4-methoxybenzyl)pyrazolo[1,5-a]pyridine-3-carboxamide (I-35) (15 mg, 0.025 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-cyano-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyridine-3-carboxamide (X-25). 1H NMR (400 MHz, CD3CN) δ 8.22 (d, J=7.8 Hz, 1 H), 8.05 (s, 1 H), 7.43-7.28 (m, 1 H), 7.10 (d, J=7.7 Hz, 1 H), 7.06-6.96 (m, 3 H), 6.38 (dd, J=2.8, 7.7 Hz, 1 H), 5.09 (dd, J=3.0, 8.1 Hz, 1 H), 4.18 (dd, J=7.6, 9.6 Hz, 1 H), 3.82-3.70 (m, 1 H), 3.49-3.34 (m, 1 H), 2.86-2.68 (m, 1 H), 2.38-2.28 (m, 1 H). MS m/z 350.1 (M+1)+.

Workup

  1. custompurified by preparative LCMS

Sources & evidence

ORD record
ord-af13821ac2e54328b3c6f618473d01d0
Source dataset
uspto-grants-2015_08
Patent number
US09102671B2

Reaction notes

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