1,1'-Carbonyldiimidazole → 6-(5-Methyl-3-phenyl-isoxazol-4-ylmethoxy)-N-(3-oxo-isoxazolidin-5-ylmethyl)-nicotinamide

HRID 83129Notes

Reaction equation

[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[CH2:13][O:14][C:15]1[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][N:16]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:36][CH2:37][CH:38]1[O:42][NH:41][C:40](=[O:43])[CH2:39]1>CN(C=O)C.C(OCC)(=O)C>[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:3]=1[CH2:13][O:14][C:15]1[CH:23]=[CH:22][C:18]([C:19]([NH:36][CH2:37][CH:38]2[O:42][NH:41][C:40](=[O:43])[CH2:39]2)=[O:21])=[CH:17][N:16]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid (200 mg, 0.64 mmol) in DMF (2 mL) was added 1,1′-carbonyl-diimidazole (115 mg, 0.71 mmol) and the reaction mixture was stirred for 0.5 h at 80° C. After cooling to ambient temperature 5-aminomethyl-isoxazolidin-3-one (82 mg, 0.71 mmol) was added and stirring was continued for 1 h at this temperature and for 2 h at 80° C. It was diluted with ethyl acetate (10 mL) and washed with water (10 mL) and aqueous sodium chloride (saturated, 10 mL). The organic layer was dried over sodium sulfate and concentrated. Purification by chromatography (SiO2, heptane:ethyl acetate:methanol=40:60:0 to 0:90:10) afforded the title compound (13 mg, 5%) as a white solid. MS: m/e=409.3 [M+H]+.

Workup

additionwas added
stirringstirring
waitwas continued for 1 h at this temperature and for 2 h at 80° C
washwashed with water (10 mL) and aqueous sodium chloride (saturated, 10 mL)
dry with materialThe organic layer was dried over sodium sulfate
concentrationconcentrated
customPurification by chromatography (SiO2, heptane:ethyl acetate:methanol=40:60:0 to 0:90:10)

Sources & evidence

ORD record: ord-25619d5b83ed493e8b2de532e3d1226b
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846719B2

Reaction notes

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