Sodium Carbonate → 7-methyl-5-{1-methyl-5-[4-(trifluoromethyl)phenyl]-1H-pyrazol-4-yl}imidazo[5,1-f][1,2,4]triazin-4(3H)-one

HRID 1907209Notes

Reaction equation

Br[C:2]1[N:6]([CH3:7])[N:5]=[CH:4][C:3]=1[C:8]1[N:9]=[C:10]([CH3:18])[N:11]2[C:16]=1[C:15](=[O:17])[NH:14][CH:13]=[N:12]2.[F:19][C:20]([F:31])([F:30])[C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:18][C:10]1[N:11]2[C:16]([C:15](=[O:17])[NH:14][CH:13]=[N:12]2)=[C:8]([C:3]2[CH:4]=[N:5][N:6]([CH3:7])[C:2]=2[C:24]2[CH:25]=[CH:26][C:21]([C:20]([F:31])([F:30])[F:19])=[CH:22][CH:23]=2)[N:9]=1

Participants

Conditions

Temperature: 100 °C

Procedure

5-(5-Bromo-1-methyl-1H-pyrazol-4-yl)-7-methylimidazo[5,1-f][1,2,4]triazin-4(3H)-one (200 mg, 0.647 mmol), [4-(trifluoromethyl)phenyl]boronic acid (96%, 128 mg, 0.647 mmol), tetrakis(triphenylphosphine)palladium(0) (60.1 mg, 0.052 mmol) and sodium carbonate (206 mg, 1.94 mmol) were combined in ethanol (4 mL) and subjected to microwave irradiation at 130° C. for 45 minutes, then heated at 100° C. for 18 hours. The solvent was removed in vacuo, and the residue was partitioned between ethyl acetate and water. The aqueous layer was extracted three times with ethyl acetate, and the combined organic layers were concentrated in vacuo and purified via silica gel chromatography (Gradient: 50% to 100% [5% methanol/5% triethylamine/90% ethyl acetate] in heptane) to provide the product. Yield: 90 mg, 0.24 mmol, 37%. LCMS m/z 375.4 (M+1). 1H NMR (400 MHz, CD3OD) δ 2.47 (s, 3H), 3.84 (s, 3H), 7.56 (br d, J=8 Hz, 2H), 7.63 (s, 1H), 7.71 (br d, J=8 Hz, 2H), 7.98 (s, 1H).

Workup

customirradiation at 130° C. for 45 minutes
customThe solvent was removed in vacuo
customthe residue was partitioned between ethyl acetate and water
extractionThe aqueous layer was extracted three times with ethyl acetate
concentrationthe combined organic layers were concentrated in vacuo
custompurified via silica gel chromatography (Gradient: 50% to 100% [5% methanol/5% triethylamine/90% ethyl acetate] in heptane)
customto provide the product

Sources & evidence

ORD record: ord-658e7e31a37949989e65e7c326ca481d
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08598155B2

Reaction notes

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