Diisopropylethylamine → HCID 67064741, compound

HRID 1256375Notes

Reaction equation

HRID 1256375 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.[F:26][CH:27]1[CH2:31][CH2:30][NH:29][CH2:28]1.C(N(CC)C(C)C)(C)C>CN(C=O)C.CS(C)=O.CO>[F:26][CH:27]1[CH2:31][CH2:30][N:29]([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)[CH2:28]1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 219752283-Fluoropyrrolidine hydrochlorideHCID 86652267N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Product 1

HCID 67064741HCID 67064741, compoundYield 74%

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, 86 mg, 0.25 mmol), 3-fluoropyrrolidine hydrochloride (63 mg, 0.75 mmol), and N,N-diisopropylethylamine (116 mg, 0.90 mmol) in DMF (1.0 mL) was stirred at 100° C. for 2 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 (30-30% MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a white solid (73.5 mg, 74%). 1H NMR (DMSO-d6) δ: 10.82 (s, 1H), 7.98 (d, J=8.6 Hz, 2H), 7.61 (d, J=8.3 Hz, 2H), 6.89 (s, 1H), 6.11 (s, 1H), 5.50 (d, J=52.0 Hz, 1H), 4.05-4.45 (m, 3H), 3.86-3.96 (m, 1H), 2.35 (s, 3H), 2.24-2.33 (m, 1H), 2.11-2.24 (m, 1H), 1.45 (s, 6H); ESI-MS: m/z 398.3 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-163c2e9baa6d47e9a1c6bd0002965f40
Source dataset
uspto-grants-2013_06
Patent number
US08461163B2

Reaction notes

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