5-Bromo-1-methyl-1H-imidazole → (2,4-Dimethylthiazol-5-yl)(1-methyl-1H-imidazol-5-yl)methanone

HRID 1478502Notes

Reaction equation

Br[C:2]1[N:6]([CH3:7])[CH:5]=[N:4][CH:3]=1.CON(C)[C:11]([C:13]1[S:17][C:16]([CH3:18])=[N:15][C:14]=1[CH3:19])=[O:12]>C1COCC1>[CH3:18][C:16]1[S:17][C:13]([C:11]([C:2]2[N:6]([CH3:7])[CH:5]=[N:4][CH:3]=2)=[O:12])=[C:14]([CH3:19])[N:15]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a flask containing 5-bromo-1-methyl-1H-imidazole (390 mg, 2.42 mmol) was added THF (8 mL) and the solution was cooled to 0° C. To this solution was added isopropylmagnesium chloride-LiC1 complex (1.3 M in THF, 2.5 mL, 3.25 mmol) which resulted in a white suspension. The reaction mixture was stirred in a 0° C. bath for 30 minutes, then a THF (2 mL) solution of N-methoxy-N,2,4-trimethylthiazole-5-carboxamide (550 mg, 2.75 mmol, Intermediate 17: step a) was introduced. The reaction mixture was stirred at 50° C. for 18 hours, cooled to room temperature and quenched with aqueous NH4Cl solution. The aqueous portion was extracted with DCM (4×50 mL) and the combined organics were washed with brine, dried over Na2SO4, filtered and concentrated. Chromatography on silica gel (25% EtOAc-DCM increasing to 5% MeOH-DCM) afforded the title compound as an amber solid.

Workup

customresulted in a white suspension
stirringThe reaction mixture was stirred at 50° C. for 18 hours
temperaturecooled to room temperature
customquenched with aqueous NH4Cl solution
extractionThe aqueous portion was extracted with DCM (4×50 mL)
washthe combined organics were washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-7ab66fdce8364f18aa724f4e35d1b3cd
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09403816B2

Reaction notes

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