Diisopropylethylamine → 1-[5-[[4-(1-Hydroxy-1-methylethyl)benzoyl]amino]-2-methylpyrazolo[1,5-a]pyrimidin-7-yl]-4-piperidineacetamide

HRID 1256402Notes

Reaction equation

HRID 1256402 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](=[O:24])[C:14]2[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=2)[CH:3]=1.Cl.[NH:26]1[CH2:31][CH2:30][CH:29]([CH2:32][C:33]([NH2:35])=[O:34])[CH2:28][CH2:27]1.C(N(CC)C(C)C)(C)C>CN(C=O)C.CS(C)=O.CO>[NH2:35][C:33](=[O:34])[CH2:32][CH:29]1[CH2:30][CH2:31][N:26]([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](=[O:24])[C:14]3[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=3)[CH:3]=2)[CH2:27][CH2:28]1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 665247942-(Piperidin-4-yl)acetamide hydrochlorideHCID 86652267N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Product 1

HCID 670647371-[5-[[4-(1-Hydroxy-1-methylethyl)benzoyl]amino]-2-methylpyrazolo[1,5-a]pyrimidin-7-yl]-4-piperidineacetamideYield 34%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (2F, 100 mg, 0.290 mmol), 2-(piperidin-4-yl)acetamide hydrochloride (82 mg, 0.58 mmol), and N,N-diisopropylethylamine (112 mg, 0.870 mmol) in DMF (2.0 mL) was stirred at 100° C. for 3 h. After cooling to room temperature, the mixture was diluted with a few drops of DMSO and methanol, and was then purified by preparatory HPLC (30-35% MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a white solid (44.4 mg, 34%). 1H NMR (DMSO-d6) δ: 10.84 (s, 1H), 7.89-8.10 (m, 2H), 7.53-7.66 (m, 2H), 7.33 (br. s., 1H), 7.28 (s, 1H), 6.81 (br. s., 1H), 6.16 (s, 1H), 4.44 (d, J=12.6 Hz, 2H), 3.00-3.12 (m, 2H), 2.37 (s, 3H), 1.94-2.14 (m, 3H), 1.81 (d, J=13.1 Hz, 2H), 1.41-1.53 (m, 6H), 1.30-1.41 (m, 2H); ESI-MS: m/z 451.2 (M+H)+.

Workup

  1. customwas then purified by preparatory HPLC (30-35% MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-c3fb9cf2ea5c47b3b4916c287b681233
Source dataset
uspto-grants-2013_06
Patent number
US08461163B2

Reaction notes

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