Dimethyl Sulfoxide → Methyl 6-(((5-methyl-3-phenylisoxazol-4-yl)methyl)amino)nicotinate

HRID 1897186Notes

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]=1NC.Cl[C:16]1[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][N:17]=1.[CH:26]([N:29](CC)C(C)C)(C)C.CS(C)=O>C(OCC)(=O)C>[CH3:23][O:22][C:20](=[O:21])[C:19]1[CH:24]=[CH:25][C:16]([NH:29][CH2:26][C:3]2[C:4]([C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=3)=[N:5][O:6][C:2]=2[CH3:1])=[N:17][CH:18]=1

Participants

Conditions

Temperature: 160 °C

Procedure

A mixture of (5-methyl-3-phenyl-4-isoxazolyl)-methylamine (200 mg, 1.06 mmol), methyl 6-chloronicotinate (182 mg, 1.06 mmol), N,N-diisopropyl ethyl amine (364 μL, 2.13 mmol) and DMSO (2 mL) was heated in the microwave to 160° C. for 0.5 h. It was diluted with ethyl acetate (8 mL) and washed with aqueous sodium carbonate (saturated, 8 mL), water (8 mL) and brine (8 mL). The combined aqueous layers were extracted with ethyl acetate (10 mL) and the combined organic layers were dried over sodium sulfate. Concentration and purification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 50:50) afforded the title compound (158 mg, 46%) as a light yellow oil. MS: m/e=324.3 [M+H]+.

Workup

washwashed with aqueous sodium carbonate (saturated, 8 mL), water (8 mL) and brine (8 mL)
extractionThe combined aqueous layers were extracted with ethyl acetate (10 mL)
dry with materialthe combined organic layers were dried over sodium sulfate
concentrationConcentration and purification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 50:50)

Sources & evidence

ORD record: ord-52e91fceaa5b4e379ac938affe938b97
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08518974B2

Reaction notes

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