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

HRID 1256387Notes

Reaction equation

HRID 1256387 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]([CH:15]2[CH2:17][CH:16]2[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:14])[CH:3]=1.[NH:24]1[CH2:29][CH2:28][CH:27]([CH2:30][CH2:31][OH:32])[CH2:26][CH2:25]1>CN1C(=O)CCC1.CS(C)=O.CO>[OH:32][CH2:31][CH2:30][CH:27]1[CH2:28][CH2:29][N:24]([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]([CH:15]3[CH2:17][CH:16]3[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:14])[CH:3]=2)[CH2:25][CH2:26]1

Participants

6

Reactant 2

HCID 739534-PiperidineethanolHCID 86652269N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-2-phenylcyclopropanecarboxamide

Product 1

HCID 66896888N-(7-(4-(2-hydroxyethyl)piperidin-1-yl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-2-phenylcyclopropanecarboxamideYield 4%

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-phenylcyclopropanecarboxamide (8C, 200 mg, 0.612 mmol) and 2-(piperidin-4-yl)ethanol (158 mg, 1.2 mmol) in NMP (1.85 mL) was stirred at 100° 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, 40-50% (MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a white solid (9 mg, 4%). 1H NMR (METHANOL-d4) δ: 7.25-7.31 (m, 2H), 7.14-7.23 (m, 4H), 6.07 (s, 1H), 4.41 (d, J=12.1 Hz, 2H), 3.67 (t, J=6.6 Hz, 2H), 2.98 (td, J=12.4, 2.4 Hz, 2H), 2.51 (ddd, J=9.2, 6.4, 4.3 Hz, 1H), 2.40 (s, 3H), 2.15-2.23 (m, 1H), 1.85 (br. s., 2H), 1.29-1.69 (m, 7H). ESI-MS: m/z 420.0 (M+H)+.

Workup

  1. customwas then purified by preparatory HPLC, 40-50% (MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-02f5e5e913ff45f2989de29588e1ffe5
Source dataset
uspto-grants-2013_06
Patent number
US08461163B2

Reaction notes

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