(S)-3-fluoropyrrolidine → N-(7-((S)-3-fluoropyrrolidin-1-yl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-2-phenylcyclopropanecarboxamide

HRID 1256393Notes

Reaction equation

HRID 1256393 reaction equation
Cl[C:2]1[N:7]2[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]2[N:5]=[C:4]([NH:12][C:13]([CH:15]2[CH2:17][CH:16]2[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:14])[CH:3]=1.[F:24][C@H:25]1[CH2:29][CH2:28][NH:27][CH2:26]1>CN1C(=O)CCC1.CS(C)=O.CO>[F:24][C@H:25]1[CH2:29][CH2:28][N:27]([C:2]2[N:7]3[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]3[N:5]=[C:4]([NH:12][C:13]([CH:15]3[CH2:17][CH:16]3[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:14])[CH:3]=2)[CH2:26]1

Participants

6

Reactant 2

HCID 7016277(S)-3-fluoropyrrolidineHCID 86652269N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-2-phenylcyclopropanecarboxamide

Product 1

HCID 67064272N-(7-((S)-3-fluoropyrrolidin-1-yl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-2-phenylcyclopropanecarboxamideYield 44%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideCatalystHCID 887MethanolSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-2-phenylcyclopropanecarboxamide (8C, 200 mg, 1.69 mmol) and (S)-3-fluoropyrrolidine (302 mg, 3.38 mmol) in NMP (5 mL) was stirred at 100° C. overnight. After cooling to room temperature, the mixture was diluted with a few drops of DMSO and methanol, and was then purified by preparatory HPLC (35-40% MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a white solid (59 mg, 44%). 1H NMR (DMSO-d6) δ: 10.87 (s, 1H), 7.26-7.35 (m, 2H), 7.13-7.24 (m, 3H), 6.83 (s, 1H), 5.99 (s, 1H), 5.29-5.58 (m, 1H), 3.72-4.50 (m, 4H), 2.40-2.47 (m, 1H), 2.22-2.36 (m, 5H), 2.15 (br. s., 1H), 1.50 (dt, J=9.2, 4.6 Hz, 1H), 1.35-1.44 (m, 1H). ESI-MS: m/z 380.0 (M+H)+.

Workup

  1. customwas then purified by preparatory HPLC (35-40% MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-ebc685fc889b4e14848a931f5ed81203
Source dataset
uspto-grants-2013_06
Patent number
US08461163B2

Reaction notes

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