Water → N-[(3-Fluorophenyl)-methyl]-4-methyl-6-morpholin-4-yl-2-(oxetan-3-yloxy)-pyridine-3-carboxylic acid amide

HRID 1753891Notes

Reaction equation

[OH:1][CH:2]1[CH2:5][O:4][CH2:3]1.CC([O-])(C)C.[K+].Cl[C:13]1[C:18]([C:19]([NH:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=2)=[O:20])=[C:17]([CH3:30])[CH:16]=[C:15]([N:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)[N:14]=1.O>C1COCC1>[F:29][C:25]1[CH:24]=[C:23]([CH2:22][NH:21][C:19]([C:18]2[C:13]([O:1][CH:2]3[CH2:5][O:4][CH2:3]3)=[N:14][C:15]([N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)=[CH:16][C:17]=2[CH3:30])=[O:20])[CH:28]=[CH:27][CH:26]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A solution of 209 mg (2.82 mmol) 3-hydroxy-oxetane in THF (6 ml) was treated with 316 mg (2.81 mmol) KOtBu and was heated at 50° C. for 15 min. After cooling to RT a solution of 205 mg (0.56 mmol) 2-chloro-N-[(3-fluorophenyl)-methyl]-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide (synthesis is described in section a) of example 9) in THF (3 ml) was added and the mixture was heated at 80° C. for 8 h. The mixture was then poured into water and extracted with EtOAc. The organic layer was washed with water and brine, dried over Na2SO4 and concentrated in vacuo. Purification of the residue by CC (hexane/EtOAc 7:3) provided 190 mg (0.47 mmol, 84%) N-[(3-Fluorophenyl)-methyl]-4-methyl-6-morpholin-4-yl-2-(oxetan-3-yloxy)-pyridine-3-carboxylic acid amide (example 317). [M+H]+402.2.

Workup

customsynthesis
additionwas added
temperaturethe mixture was heated at 80° C. for 8 h
extractionextracted with EtOAc
washThe organic layer was washed with water and brine
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customPurification of the residue by CC (hexane/EtOAc 7:3)

Sources & evidence

ORD record: ord-2981e1e6c98841629687ada879852971
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09168259B2

Reaction notes

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