4-Piperidinemethanol → N-(7-(4-(hydroxymethyl)piperidin-1-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

HRID 1409168Notes

Reaction equation

HRID 1409168 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.[NH:24]1[CH2:29][CH2:28][CH:27]([CH2:30][OH:31])[CH2:26][CH2:25]1>CN1C(=O)CCC1.CS(C)=O.CO>[OH:31][CH2:30][CH:27]1[CH2:28][CH2:29][N:24]([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)[CH2:25][CH2:26]1

Participants

6

Reactant 2

HCID 4207714-PiperidinemethanolHCID 86652272N-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Product 1

HCID 67063920N-(7-(4-(hydroxymethyl)piperidin-1-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamideYield 89%

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 piperidin-4-ylmethanol (35 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, 20-50% (MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a white solid (55 mg, 89%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.46 (s, 8H) 1.65-1.95 (m, 3H) 2.96-3.15 (m, 2H) 3.34 (d, J=6.06 Hz, 2H) 4.39-4.56 (m, 2H) 6.35 (d, J=2.02 Hz, 1H) 7.38 (s, 1H) 7.60 (d, J=8.59 Hz, 2H) 8.00 (d, J=8.59 Hz, 2H) 8.08 (d, J=2.27 Hz, 1H) 10.87 (s, 1H). ESI-MS: m/z 410.3 (M+H)+.

Workup

  1. customwas then purified by preparatory HPLC, 20-50% (MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-2703939dadb24f5cb922ab18ae40c5ca
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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