4-Acetamidopiperidine → (1R,2R)-N-(7-(4-acetamidopiperidin-1-yl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-2-phenylcyclopropanecarboxamide

HRID 1256428Notes

Reaction equation

HRID 1256428 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.[NH:24]1[CH2:29][CH2:28][CH:27]([NH:30][C:31](=[O:33])[CH3:32])[CH2:26][CH2:25]1>CN1C(=O)CCC1.CS(C)=O.CO>[C:31]([NH: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]([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]=2)[CH2:25][CH2:26]1)(=[O:33])[CH3:32]

Participants

6

Reactant 2

HCID 14451564-AcetamidopiperidineHCID 86652282(1R,2R)-N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-2-phenylcyclopropanecarboxamide

Product 1

HCID 67064435(1R,2R)-N-(7-(4-acetamidopiperidin-1-yl)-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-2-phenylcyclopropanecarboxamideYield 66%

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-phenylcyclopropane carboxamide (8D, 0.1 g, 0.306 mmol) and the N-(piperidin-4-yl)acetamide (0.087 g, 0.612 mmol) in NMP (Volume: 1.020 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 45-65% preparatory HPLC (MeCN/MeOH)/H2O+0.01% TFA). Lyophilization of the combined fractions gave 87 mg (66%) of the titled compound as a white solid. Melting point (190.2-231.1° C.). 1H NMR (DMSO-d6) δ: 10.95 (s, 1H), 7.91 (d, J=7.8 Hz, 1H), 7.23-7.37 (m, 3H), 7.12-7.24 (m, 3H), 6.08 (s, 1H), 4.30 (d, J=12.9 Hz, 2H), 3.88 (br. s., 1H), 3.16 (dd, J=24.3, 11.6 Hz, 2H), 2.39-2.47 (m, 1H), 2.25-2.38 (m, 4H), 1.89 (d, J=13.6 Hz, 2H), 1.82 (s, 3H), 1.46-1.62 (m, 3H), 1.40 (ddd, J=8.2, 6.4, 4.0 Hz, 1H); [α]D20=+218° (C=0.6917, MeOH). ESI-MS: m/z 433.0 (M+H)+. Melting point (190.2-231.1° C.).

Workup

  1. customThe title compound was prepared
  2. customwas then purified by 45-65% preparatory HPLC (MeCN/MeOH)/H2O+0.01% TFA)

Sources & evidence

ORD record
ord-e81d560132e247329786e9dce50f1a08
Source dataset
uspto-grants-2013_06
Patent number
US08461163B2

Reaction notes

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