(3R)-(+)-3-(Dimethylamino)pyrrolidine → HCID 67064054, compound

HRID 1409164Notes

Reaction equation

HRID 1409164 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.[CH3:24][N:25]([CH3:31])[C@@H:26]1[CH2:30][CH2:29][NH:28][CH2:27]1>CN1C(=O)CCC1.CS(C)=O.CO>[CH3:24][N:25]([CH3:31])[C@@H:26]1[CH2:30][CH2:29][N:28]([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)[CH2:27]1

Participants

6

Reactant 2

HCID 2758521(3R)-(+)-3-(Dimethylamino)pyrrolidineHCID 86652272N-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Product 1

HCID 67064054HCID 67064054, compoundYield 97.3%

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 (R)—N,N-dimethylpyrrolidin-3-amine (34 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, 10-35% (MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a white solid (60 mg, 97%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.45 (s, 6H) 2.22-2.35 (m, 2H) 2.90 (d, J=3.79 Hz, 6H) 3.78-3.91 (m, 1H) 4.01-4.16 (m, 2H) 4.35 (d, J=6.57 Hz, 2H) 6.26 (d, J=2.27 Hz, 1H) 7.15 (s, 1H) 7.60 (d, J=8.34 Hz, 2H) 7.99 (d, J=8.34 Hz, 2H) 8.04 (d, J=2.27 Hz, 1H) 9.88 (br. s., 1H) 10.77 (s, 1H). ESI-MS: m/z 409.3 (M+H)+.

Workup

  1. customwas then purified by preparatory HPLC, 10-35% (MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-2a78225f0b8d46b381bde1b7dca08a1b
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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