Pyrrolidine, 3-fluoro- → HCID 67064572, compound

HRID 1409156Notes

Reaction equation

HRID 1409156 reaction equation
Cl[C:2]1[N:7]2[N:8]=[CH:9][CH:10]=[C:6]2[N:5]=[C:4]([NH:11][C:12](=[O:23])[C:13]2[CH:18]=[CH:17][C:16]([C:19]([OH:22])([CH3:21])[CH3:20])=[CH:15][CH:14]=2)[CH:3]=1.[F:24][CH:25]1[CH2:29][CH2:28][NH:27][CH2:26]1>CN1C(=O)CCC1.CS(C)=O.CO>[F:24][CH:25]1[CH2:29][CH2:28][N:27]([C:2]2[N:7]3[N:8]=[CH:9][CH:10]=[C:6]3[N:5]=[C:4]([NH:11][C:12](=[O:23])[C:13]3[CH:18]=[CH:17][C:16]([C:19]([OH:22])([CH3:21])[CH3:20])=[CH:15][CH:14]=3)[CH:3]=2)[CH2:26]1

Participants

6

Reactant 2

HCID 3744989Pyrrolidine, 3-fluoro-HCID 86652272N-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Product 1

HCID 67064572HCID 67064572, compoundYield 54%

Reagents, catalysts & solvents 3

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

Procedure

A solution of N-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (2D, 50 mg, 0.151 mmol) and 3-fluoropyrrolidine (27 mg, 0.302 mmol) in NMP (0.950 mL) was stirred at 85° 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, 25-50% (MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a white solid (31 mg, 54%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.45 (s, 6H) 2.02-2.45 (m, 2H) 3.86-4.02 (m, 1H) 4.05-4.47 (m, 3H) 5.35-5.64 (m, 1H) 6.26 (s, 1H) 7.01 (br. s., 1H) 7.60 (d, J=8.34 Hz, 2H) 7.88-8.10 (m, 3H) 10.80 (br. s., 1H). ESI-MS: m/z 384.2 (M+H)+.

Workup

  1. customwas then purified by preparatory HPLC, 25-50% (MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-3af4419ce64c4011acad3d1f94ade885
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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