3-Fluoropyrrolidine → HCID 67064469, compound

HRID 1409236Notes

Reaction equation

HRID 1409236 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 27591633-FluoropyrrolidineHCID 86652269N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-2-phenylcyclopropanecarboxamide

Product 1

HCID 67064469HCID 67064469, compoundYield 26%

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, 0.612 mmol) and (R)-3-fluoropyrrolidine (109 mg, 1.22 mmol) in NMP (1.85 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 (60 mg, 26%). 1H NMR (DMSO-d6) δ: 10.77 (s, 1H), 7.24-7.35 (m, 2H), 7.11-7.25 (m, 3H), 6.93 (s, 2H), 5.95 (s, 1H), 5.30-5.61 (m, 1H), 3.74-4.41 (m, 4H), 2.01-2.47 (m, 6H), 1.48 (dt, J=9.0, 4.7 Hz, 1H), 1.29-1.42 (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-b310bea47f8f4958b6cee3a2a59daed7
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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