Diisopropylethylamine → 4-(2-hydroxypropan-2-yl)-N-(2-methyl-7-(4-ureidopiperidin-1-yl)pyrazolo[1,5-a]pyrimidin-5-yl)benzamide

HRID 1409246Notes

Reaction equation

HRID 1409246 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]([NH: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>[OH:23][C:20]([C:17]1[CH:18]=[CH:19][C:14]([C:13]([NH:12][C:4]2[CH:3]=[C:2]([N:26]3[CH2:31][CH2:30][CH:29]([NH:32][C:33]([NH2:35])=[O:34])[CH2:28][CH2:27]3)[N:7]3[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]3[N:5]=2)=[O:24])=[CH:15][CH:16]=1)([CH3:22])[CH3:21]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 17750380(Piperidin-4-yl)urea hydrochlorideHCID 86652267N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Product 1

HCID 670644904-(2-hydroxypropan-2-yl)-N-(2-methyl-7-(4-ureidopiperidin-1-yl)pyrazolo[1,5-a]pyrimidin-5-yl)benzamideYield 45.4%

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), 1-(piperidin-4-yl)urea hydrochloride (83 mg, 0.580 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 (25-35% MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a white solid (59.4 mg, 45%). Decomposition was observed at 225.4° C. 1H NMR (DMSO-d6) δ: 10.81 (s, 1H), 7.92 (d, J=8.6 Hz, 2H), 7.53 (d, J=8.6 Hz, 2H), 7.23 (s, 1H), 6.11 (s, 1H), 6.06 (br. s., 1H), 4.26 (d, J=12.9 Hz, 2H), 3.63 (t, J=9.6 Hz, 1H), 3.17 (t, J=11.0 Hz, 2H), 2.31 (s, 3H), 1.88 (dd, J=13.0, 2.9 Hz, 2H), 1.40-1.53 (m, 2H), 1.39 (s, 6H); ESI-MS: m/z 452.2 (M+H)+.

Workup

  1. customwas then purified by preparatory HPLC (25-35% MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-488835c5e74f42e2a47305d4c3bda321
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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