Benzyl isocyanate → N-benzyl-N'-{4-[4-(3-bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}urea

HRID 1663477Notes

Reaction equation

[NH2:1][C:2]1[C:3]([C:7]2[N:11]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[C:14]([Br:19])[CH:13]=3)[C:10](=[O:20])[O:9][N:8]=2)=[N:4][O:5][N:6]=1.[CH2:21]([N:28]=[C:29]=[O:30])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[CH2:21]([NH:28][C:29]([NH:1][C:2]1[C:3]([C:7]2[N:11]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[C:14]([Br:19])[CH:13]=3)[C:10](=[O:20])[O:9][N:8]=2)=[N:4][O:5][N:6]=1)=[O:30])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

Conditions

Temperature: 150 °C

Procedure

A solution of 3-(4-amino-1,2,5-oxadiazol-3-yl)-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one (30 mg, 88 μmol) and 4-dimethylaminopyridine (5 mg, 40 μmol) in pyridine (0.5 mL) was treated with benzyl isocyanate (29 mg, 0.2 mmol) and heated in the microwave at 150° C. for 20 min. The reaction mixture was concentrated and purified by preparative LCMS to give the intermediate N-benzyl-N′-{4-[4-(3-bromo-4-fluorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}urea. This material was diluted with ethanol (1.5 mL), treated with 2.0 M sodium hydroxide in water (0.3 mL), and stirred for 30 min. Purification of the crude reaction mixture by preparative HPLC gave the desired product (11 mg, 28%). LCMS for C17H15BrFN6O3 (M+H)+: m/z=448.9, 451.0.

Workup

concentrationThe reaction mixture was concentrated
custompurified by preparative LCMS

Sources & evidence

ORD record: ord-ccbe141d4e69463ca1b1b2b1c5ce4f5c
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08034953B2

Reaction notes

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