(Piperidin-4-yl)urea hydrochloride → N-(2-methyl-7-(4-ureidopiperidin-1-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-2-(pyridin-4-yl)cyclopropanecarboxamide

HRID 1409259Notes

Reaction equation

HRID 1409259 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]([C@@H:15]2[CH2:17][C@H:16]2[C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)=[O:14])[CH:3]=1.Cl.[NH:25]1[CH2:30][CH2:29][CH:28]([NH:31][C:32]([NH2:34])=[O:33])[CH2:27][CH2:26]1>CN1C(=O)CCC1.CS(C)=O.CO>[CH3:11][C:9]1[CH:10]=[C:6]2[N:5]=[C:4]([NH:12][C:13]([CH:15]3[CH2:17][CH:16]3[C:18]3[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=3)=[O:14])[CH:3]=[C:2]([N:25]3[CH2:30][CH2:29][CH:28]([NH:31][C:32]([NH2:34])=[O:33])[CH2:27][CH2:26]3)[N:7]2[N:8]=1

Participants

6

Reactant 2

HCID 17750380(Piperidin-4-yl)urea hydrochlorideHCID 86652268HCID 86652268, compound

Product 1

HCID 67064441N-(2-methyl-7-(4-ureidopiperidin-1-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-2-(pyridin-4-yl)cyclopropanecarboxamideYield 5.9%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideCatalystHCID 887MethanolSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-2-(pyridin-4-yl)cyclopropanecarboxamide (7E, 154 mg, 0.469 mmol) and 1-(piperidin-4-yl)urea hydrochloride (169 mg, 0.939 mmol) in NMP (1.5 mL) was stirred at room temperature 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 (10-40% MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a white solid (12 mg, 2%). 1H NMR (DMSO-d6) δ: 10.97 (s, 1H), 8.33-8.52 (m, 2H), 7.07-7.37 (m, 4H), 6.08 (s, 2H), 5.41 (s, 2H), 4.24 (br. s., 2H), 3.65 (br. s., 2H), 3.16 (br. s., 2H), 2.35 (s, 3H), 1.89 (br. s., 2H), 1.50 (br. s., 4H). ESI-MS: m/z 435.0 (M+H)+.

Workup

  1. customwas then purified by preparatory HPLC (10-40% MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-8ff926490ffa433585dfb9db5c8bdfc7
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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