Formamide → methyl[4-(5-bromo-1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl]carbamate

HRID 1498047Notes

Reaction equation

[Br:1][C:2]1[N:6]([CH3:7])[N:5]=[CH:4][C:3]=1[C:8](=O)[CH2:9][N:10]([CH:16]=O)[NH:11][C:12]([O:14][CH3:15])=[O:13].C([O-])(=O)C.[NH4+].C([NH2:26])=O.C(#N)C>O>[CH3:15][O:14][C:12](=[O:13])[NH:11][N:10]1[CH:9]=[C:8]([C:3]2[CH:4]=[N:5][N:6]([CH3:7])[C:2]=2[Br:1])[N:26]=[CH:16]1

Participants

Conditions

Temperature: 130 °C

Procedure

Methyl 2-[2-(5-bromo-1-methyl-1H-pyrazol-4-yl)-2-oxoethyl]-2-formylhydrazine carboxylate (1.20 g, 3.76 mmol) was mixed with ammonium acetate (1.16 g, 15.0 mmol), formamide (4 mL) and acetonitrile (5 mL). The reaction was heated to 130° C., and the acetonitrile was allowed to boil off for 10 minutes. Heating was continued for an additional 4 hours. After addition of water, the crude mixture was extracted eight times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo; purification via silica gel chromatography (Gradient: 0% to 100% [10% methanol in ethyl acetate] in heptane) afforded the product as a pinkish solid. Yield: 800 mg, 2.67 mmol, 19% over two steps. LCMS m/z 299.8 (M+1). 1H NMR (400 MHz, CD3OD) δ 3.80 (br s, 3H), 3.90 (s, 3H), 7.52 (d, J=1.3 Hz, 1H), 7.77 (d, J=1.3 Hz, 1H), 7.85 (s, 1H).

Workup

temperatureHeating
waitwas continued for an additional 4 hours
extractionthe crude mixture was extracted eight times with ethyl acetate
dry with materialThe combined organic layers were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
custompurification via silica gel chromatography (Gradient: 0% to 100% [10% methanol in ethyl acetate] in heptane)

Sources & evidence

ORD record: ord-5c202d5aa6d24e4da14388fc90d903bc
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09200000B2

Reaction notes

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