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

HRID 1256429Notes

Reaction equation

HRID 1256429 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][CH: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]([C@@H:15]3[CH2:17][C@H:16]3[C:18]3[CH:23]=[CH:22][CH: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 86652282(1R,2R)-N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-2-phenylcyclopropanecarboxamide

Product 1

HCID 67064269(1R,2R)-N-(2-methyl-7-(4-ureidopiperidin-1-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-2-phenylcyclopropanecarboxamideYield 59.3%

Reagents, catalysts & solvents 3

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

Procedure

The title compound was prepared by combining (1R,2R)—N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-2-phenylcyclopropanecarboxamide (8D, 0.08 g, 0.245 mmol) and the 1-(piperidin-4-yl)urea hydrochloride (0.088 g, 0.490 mmol) in NMP (0.816 ml) and heating the mixture 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 40-60% preparatory HPLC (ACN/MeOH)/H2O+0.01% TFA). Lyophilization of the combined fractions gave 63 mg (59%) of the titled compound as a yellow solid. Melting point (160.1-165.7° C.). 1H NMR (DMSO-d6) δ: 10.95 (s, 1H), 7.24-7.35 (m, 3H), 7.14-7.24 (m, 3H), 6.08 (s, 3H), 4.24 (d, J=13.1 Hz, 2H), 3.66 (br. s., 2H), 3.17 (dd, J=23.7, 12.1 Hz, 2H), 2.39-2.47 (m, 1H), 2.26-2.38 (m, 4H), 1.90 (d, J=13.1 Hz, 2H), 1.34-1.59 (m, 4H); [α]D20=−202° (c=0.714, MeOH). ESI-MS: m/z 434.0 (M+H)+. Melting point (160.1-165.7° C.).

Workup

  1. customThe title compound was prepared
  2. customwas then purified by 40-60% preparatory HPLC (ACN/MeOH)/H2O+0.01% TFA)

Sources & evidence

ORD record
ord-e5094e7081de46b7a5b528f55263073b
Source dataset
uspto-grants-2013_06
Patent number
US08461163B2

Reaction notes

Loading…