4-Piperidineethanol → N-(7-(4-(2-hydroxyethyl)piperidin-1-yl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

HRID 1256376Notes

Reaction equation

HRID 1256376 reaction equation
Cl[C:2]1[N:7]2[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]2[N:5]=[C:4]([NH:12][C:13](=[O:24])[C:14]2[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=2)[CH:3]=1.[NH:25]1[CH2:30][CH2:29][CH:28]([CH2:31][CH2:32][OH:33])[CH2:27][CH2:26]1>CN(C=O)C.CS(C)=O.CO>[OH:33][CH2:32][CH2:31][CH:28]1[CH2:29][CH2:30][N:25]([C:2]2[N:7]3[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]3[N:5]=[C:4]([NH:12][C:13](=[O:24])[C:14]3[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=3)[CH:3]=2)[CH2:26][CH2:27]1

Participants

6

Reactant 2

HCID 739534-PiperidineethanolHCID 86652267N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Product 1

HCID 67064624N-(7-(4-(2-hydroxyethyl)piperidin-1-yl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamideYield 58.4%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (2F, 86 mg, 0.25 mmol) and 2-(piperidin-4-yl)ethanol (100 mg, 0.75 mmol) in DMF (1.0 mL) was stirred at 100° C. for 2 h. After cooling to room temperature, the mixture was diluted with a few drops of DMSO and methanol, and was then purified by preparatory HPLC (30-35% MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a white solid (63.9 mg, 58%). Melting point (234.0-234.1° C.). 1H NMR (DMSO-d6) δ: 10.93 (s, 1H), 8.00 (d, J=8.6 Hz, 2H), 7.61 (d, J=8.6 Hz, 2H), 7.20 (s, 1H), 6.20 (s, 1H), 4.51 (d, J=12.6 Hz, 2H), 3.50 (t, J=6.4 Hz, 2H), 3.07 (t, J=11.5 Hz, 2H), 2.38 (s, 3H), 1.84 (d, J=12.9 Hz, 2H), 1.68-1.81 (m, 1H), 1.46 (s, 6H), 1.41-1.45 (m, 2H), 1.29-1.41 (m, 2H); ESI-MS: m/z 438.3 (M+H)+.

Workup

  1. customwas then purified by preparatory HPLC (30-35% MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-2b4ba3bdc55b46338ac4c1531cad4d34
Source dataset
uspto-grants-2013_06
Patent number
US08461163B2

Reaction notes

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