3-Hydroxyazetidine → HCID 67064613, compound

HRID 1409154Notes

Reaction equation

HRID 1409154 reaction equation
Cl[C:2]1[N:7]2[N:8]=[CH:9][CH:10]=[C:6]2[N:5]=[C:4]([NH:11][C:12](=[O:23])[C:13]2[CH:18]=[CH:17][C:16]([C:19]([OH:22])([CH3:21])[CH3:20])=[CH:15][CH:14]=2)[CH:3]=1.[NH:24]1[CH2:27][CH:26]([OH:28])[CH2:25]1>CN1C(=O)CCC1.CS(C)=O.CO>[OH:28][CH:26]1[CH2:27][N:24]([C:2]2[N:7]3[N:8]=[CH:9][CH:10]=[C:6]3[N:5]=[C:4]([NH:11][C:12](=[O:23])[C:13]3[CH:18]=[CH:17][C:16]([C:19]([OH:22])([CH3:21])[CH3:20])=[CH:15][CH:14]=3)[CH:3]=2)[CH2:25]1

Participants

6

Reactant 2

HCID 15142903-HydroxyazetidineHCID 86652272N-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide

Product 1

HCID 67064613HCID 67064613, compoundYield 32%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideCatalystHCID 887MethanolSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of N-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (2D, 50 mg, 151 mmol) and azetidin-3-ol (22 mg, 0.302 mmol) in NMP (0.950 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, 15-40% (MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a white solid (17 mg, 32%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.45 (s, 6H) 4.21 (br. s., 2H) 4.52-4.89 (m, 3H) 6.22 (d, J=2.27 Hz, 1H) 6.74 (s, 1H) 7.60 (d, J=8.59 Hz, 2H) 7.91-8.10 (m, 3H) 10.79 (s, 1H). ESI-MS: m/z 368.2 (M+H)+.

Workup

  1. customwas then purified by preparatory HPLC, 15-40% (MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-f3a1e10a74d84fe891c32f66870b3de5
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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