3-Methylpiperidin-4-one → 4-(2-hydroxypropan-2-yl)-N-(7-(3-methyl-4-oxopiperidin-1-yl)pyrazolo[1,5-a]pyrimidin-5-yl)benzamide

HRID 1409159Notes

Reaction equation

HRID 1409159 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[C:30](=[O:31])[CH2:29][CH2:28][NH:27][CH2:26]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:27]3[CH2:28][CH2:29][C:30](=[O:31])[CH:25]([CH3:24])[CH2:26]3)[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 122842773-Methylpiperidin-4-oneHCID 86652272N-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Product 1

HCID 670646554-(2-hydroxypropan-2-yl)-N-(7-(3-methyl-4-oxopiperidin-1-yl)pyrazolo[1,5-a]pyrimidin-5-yl)benzamideYield 56%

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-methylpiperidin-4-one (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, 30-55% (MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a white solid (34 mg, 56%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.02 (d, J=6.57 Hz, 3H) 1.46 (s, 6H) 2.74-2.97 (m, 2H) 3.30 (t, J=11.87 Hz, 1H) 3.57-3.69 (m, 1H) 4.56-4.70 (m, 2H) 6.38 (d, J=2.27 Hz, 1H) 7.48 (s, 1H) 7.60 (d, J=8.59 Hz, 2H) 8.00 (d, J=8.59 Hz, 2H) 8.13 (d, J=2.27 Hz, 1H) 10.93 (s, 1H). ESI-MS: m/z 408.2 (M+H)+.

Workup

  1. customwas then purified by preparatory HPLC, 30-55% (MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-b4ea9a74eec44b4ba2d0892e83107e1d
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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