1,1'-Carbonyldiimidazole → 6-[3-(4-Fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-N-(3-methyl-oxetan-3-yl)-nicotinamide

HRID 1514690Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([CH2:13][O:14][C:15]3[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][N:16]=3)=[C:11]([CH2:24][OH:25])[O:10][N:9]=2)=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:38][C:39]1([NH2:43])[CH2:42][O:41][CH2:40]1>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([CH2:13][O:14][C:15]3[CH:23]=[CH:22][C:18]([C:19]([NH:43][C:39]4([CH3:38])[CH2:42][O:41][CH2:40]4)=[O:21])=[CH:17][N:16]=3)=[C:11]([CH2:24][OH:25])[O:10][N:9]=2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 6-[3-(4-fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-nicotinic acid (100 mg, 0.29 mmol) in DMF (3.3 mL) was added 1,1′-carbonyl-diimidazole (58.2 mg, 0.35 mmol). The reaction mixture was stirred for 1 h at 60° C. 3-Methyl-3-oxetanamine (27.8 mg, 0.32 mmol) was then added at room temperature and the mixture was stirred overnight. Extraction with water/ethyl acetate and chromatography (silica, ethyl acetate:heptane=1:4 to 1:1) afforded the title compound (10 mg, 8%) as a white solid. MS: m/e=414.2 [M+H]+.

Workup

stirringthe mixture was stirred overnight
extractionExtraction with water/ethyl acetate and chromatography (silica, ethyl acetate:heptane=1:4 to 1:1)

Sources & evidence

ORD record: ord-0442391ff2944452ad2f475920936ff4
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08222246B2

Reaction notes

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