4-Hydroxypyrrolidine → HCID 67064172, compound

HRID 1409191Notes

Reaction equation

HRID 1409191 reaction equation
Cl[C:2]1[N:7]2[N:8]=[C:9](C)[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][CH:27]([OH:30])[CH2:26]1>O1CCOCC1.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:25]3[CH2:29][CH2:28][CH:27]([OH:30])[CH2:26]3)[N:7]3[N:8]=[CH:9][CH:10]=[C:6]3[N:5]=2)=[O:24])=[CH:15][CH:16]=1)([CH3:22])[CH3:21]

Participants

6

Reactant 2

HCID 982104-HydroxypyrrolidineHCID 86652267N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Product 1

HCID 67064172HCID 67064172, compoundYield 23%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideCatalystHCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of N-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (2D, 200 mg, 0.604 mmol) and pyrrolidin-3-ol (80 mg, 0.906 mmol) in Dioxane (6 mL) was stirred 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 preparatory HPLC, 5-95% (MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a white solid (52.5 mg, 23%). 1H NMR (400 MHz, DMSO-d6) δ: 10.63 (s, 1H), 7.82-8.10 (m, 3H), 7.58 (d, 2H), 7.05 (s, 1H), 6.17 (d, J=2.3 Hz, 1H), 5.17 (s, 1H), 5.10 (d, J=3.3 Hz, 1H), 4.43 (br. s., 1H), 3.87-4.13 (m, 4H), 1.87-2.12 (m, 2H), 1.45 (s, 6H). ESI-MS: m/z 382.0 (M+H)+.

Workup

  1. customwas then purified by preparatory HPLC, 5-95% (MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-af64e0ad1f944112ac624589316bf20c
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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