L-Prolinol → HCID 67064656, compound

HRID 1409207Notes

Reaction equation

HRID 1409207 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.[NH:25]1[CH2:29][CH2:28][CH2:27][C@H:26]1[CH2:30][OH:31]>CN(C=O)C.CS(C)=O.CO>[OH:31][CH2:30][C@@H:26]1[CH2:27][CH2:28][CH2:29][N:25]1[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

Participants

6

Reactant 2

HCID 640091L-ProlinolHCID 86652267N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Product 1

HCID 67064656HCID 67064656, compoundYield 81%

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) and (S)-pyrrolidin-2-ylmethanol (78 mg, 0.75 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 (25-25% MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a white solid (82.8 mg, 81%). Melting point (167.0-197.7° C.). 1H NMR (DMSO-d6) δ: 11.06 (s, 1H), 7.99 (d, J=8.6 Hz, 2H), 7.64 (d, J=8.6 Hz, 2H), 6.80 (s, 1H), 6.21 (s, 1H), 5.01 (br. s., 1H), 3.99 (t, J=8.2 Hz, 1H), 3.77-3.92 (m, 1H), 3.55-3.62 (m, 1H), 3.49 (dd, J=10.9, 6.6 Hz, 1H), 2.36 (s, 3H), 2.02-2.18 (m, 3H), 1.88-2.00 (m, 1H), 1.46 (s, 6H); ESI-MS: m/z 410.3 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-08f1acc51b3440ccb6830e45157b009b
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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