(R)-3-Pyrrolidinol → HCID 67064056, compound

HRID 1409172Notes

Reaction equation

HRID 1409172 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][C@@H:27]([OH:30])[CH2:26]1>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:25]3[CH2:29][CH2:28][C@@H:27]([OH:30])[CH2:26]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

6

Reactant 2

HCID 2759337(R)-3-PyrrolidinolHCID 86652267N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Product 1

HCID 67064056HCID 67064056, compoundYield 35.3%

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, 52 mg, 0.151 mmol) and (R)-pyrrolidin-3-ol (53 mg, 0.603 mmol) in DMF (0.5 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 (25-25% MeCN/H2O+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a white solid (21.1 mg, 35%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.46 (s, 6H), 1.91-2.12 (m, 2H), 2.34 (s, 3H), 3.82-4.13 (m, 5H), 4.44 (br. s., 1H), 6.16 (s, 1H), 6.71 (s, 1H), 7.63 (d, J=8.59 Hz, 2H), 7.98 (d, J=8.34 Hz, 2H), 10.95 (s, 1H); ESI-MS: m/z 396.2 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-cdf3146c1041402fa4d9bac842d47284
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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