2-Methylpyrrolidine → 4-(2-hydroxypropan-2-yl)-N-(7-(2-methylpyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-5-yl)benzamide

HRID 1256314Notes

Reaction equation

HRID 1256314 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][CH:25]1[CH2:29][CH2:28][CH2:27][NH:26]1>CN1C(=O)CCC1.CS(C)=O.CO>[OH:22][C:19]([C:16]1[CH:17]=[CH:18][C:13]([C:12]([NH:11][C:4]2[CH:3]=[C:2]([N:26]3[CH2:27][CH2:28][CH2:29][CH:25]3[CH3:24])[N:7]3[N:8]=[CH:9][CH:10]=[C:6]3[N:5]=2)=[O:23])=[CH:14][CH:15]=1)([CH3:21])[CH3:20]

Participants

6

Reactant 2

HCID 130032-MethylpyrrolidineHCID 86652272N-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Product 1

HCID 670639594-(2-hydroxypropan-2-yl)-N-(7-(2-methylpyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-5-yl)benzamideYield 59%

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, 151 mmol) and 2-methylpyrrolidine (26 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 orange solid (34 mg, 59%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.26 (d, J=6.06 Hz, 3 H) 1.45 (s, 6 H) 1.71-1.81 (m, 1 H) 1.90-2.01 (m, 1 H) 2.03-2.26 (m, 2 H) 3.75-3.91 (m, 1 H) 3.96-4.12 (m, 1 H) 4.96 (br. s., 1 H) 6.27 (d, J=2.27 Hz, 1 H) 6.98 (s, 1 H) 7.61 (d, J=8.34 Hz, 2 H) 7.91-8.09 (m, 3 H) 10.81 (s, 1 H). ESI-MS: m/z 380.3 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-f8b30685b03a457087a53821a1ae78d0
Source dataset
uspto-grants-2013_06
Patent number
US08461163B2

Reaction notes

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