N-methyl-2-pyrrolidone → N-(7-(4-acetamidopiperidin-1-yl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-2-(4-fluorophenyl)cyclopropanecarboxamide

HRID 1256431Notes

Reaction equation

HRID 1256431 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][C:21]([F:24])=[CH:20][CH:19]=2)=[O:14])[CH:3]=1.C[N:26]1[C:30](=[O:31])[CH2:29][CH2:28][CH2:27]1>CS(C)=O.CO>[C:30]([NH:26][CH:27]1[CH2:28][CH2:6][N:5]([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][C:21]([F:24])=[CH:20][CH:19]=3)=[O:14])[CH:3]=2)[CH2:4][CH2:3]1)(=[O:31])[CH3:29]

Participants

5

Reactant 2

HCID 13387N-methyl-2-pyrrolidoneHCID 86652284N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-2-(4-fluorophenyl)cyclopropanecarboxamide2×

Product 1

HCID 67064281N-(7-(4-acetamidopiperidin-1-yl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-2-(4-fluorophenyl)cyclopropanecarboxamideYield 44%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideCatalystHCID 887MethanolSolvent

Procedure

The title compound was prepared by combining N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-2-(4-fluorophenyl)cyclopropanecarboxamide (13B, 0.15 g, 0.435 mmol) and the N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-2-(4-fluorophenyl)cyclopropanecarboxamide (0.15 g, 0.435 mmol) in NMP (Volume: 1.450 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 preparatory 60-70% HPLC ([1:1 MeCN/MeOH]/H2O+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a tan solid (86 mg, 44%). 1HNMR (DMSO-d6) δ: 10.95 (s, 1H), 7.91 (d, J=7.8 Hz, 1H), 7.18-7.29 (m, 5H), 7.03-7.17 (m, 4H), 6.08 (s, 1H), 4.30 (d, J=13.1 Hz, 2H), 3.16 (t, J=12.1 Hz, 2H), 2.38-2.48 (m, 2H), 2.35 (s, 3H), 2.24-2.32 (m, 1H), 1.88 (d, J=12.9 Hz, 2H), 1.82 (s, 3H), 1.44-1.62 (m, 4H), 1.35-1.43 (m, 2H), 1.25-1.35 (m, 1H); ESI-MS: m/z 451.3 (M+H)+. It was noted that rotamers were present.

Workup

  1. customThe title compound was prepared
  2. customwas then purified by preparatory 60-70% HPLC ([1:1 MeCN/MeOH]/H2O+0.01% TFA)

Sources & evidence

ORD record
ord-48adf0c19c6d45bbb15181e789085be8
Source dataset
uspto-grants-2013_06
Patent number
US08461163B2

Reaction notes

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