2,4-Difluoroaniline → 8-(2,4-difluorophenyl)-3-(2,4-difluorophenylamino)-1-methylpyrido[3,2-d]pyridazin-2(1H)-one

HRID 1966388Notes

Reaction equation

Br[C:2]1[C:11](=[O:12])[N:10]([CH3:13])[C:9]2[C:8]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=3[F:21])=[N:7][N:6]=[CH:5][C:4]=2[CH:3]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[F:70][C:71]1[CH:76]=[C:75]([F:77])[CH:74]=[CH:73][C:72]=1[NH2:78]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:21][C:15]1[CH:16]=[C:17]([F:20])[CH:18]=[CH:19][C:14]=1[C:8]1[C:9]2[N:10]([CH3:13])[C:11](=[O:12])[C:2]([NH:78][C:72]3[CH:73]=[CH:74][C:75]([F:77])=[CH:76][C:71]=3[F:70])=[CH:3][C:4]=2[CH:5]=[N:6][N:7]=1

Participants

Conditions

Temperature: 110 °C

Procedure

To a suspension of 3-bromo-8-(2,4-difluorophenyl)-1-methylpyrido[3,2-d]pyridazin-2(1H)-one (8) (60.0 mg, 0.170 mmol) in toluene (2 mL) was added palladium (II) acetate (1.91 mg, 0.00852 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos) (9.86 mg, 0.0170 mmol) and cesium carbonate (83.3 mg, 0.256 mmol) followed by 2,4-difluorobenzenamine (0.0260 mL, 0.256 mmol). The reaction mixture was stirred and heated in a microwave at 110° C. for 75 min and then cooled to RT to afford a suspension. The solid was collected by suction filtration, washed with toluene and water, and dried in vacuo to give 8-(2,4-difluorophenyl)-3-(2,4-difluorophenylamino)-1-methylpyrido[3,2-d]pyridazin-2(1H)-one as a pale yellow solid. MS (ESI, pos. ion) m/z: 401 (M+1).

Workup

temperaturecooled to RT
customto afford a suspension
filtrationThe solid was collected by suction filtration
washwashed with toluene and water
customdried in vacuo

Sources & evidence

ORD record: ord-3eeee4d3b1af4267978b2c55c24ab616
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08420649B2

Reaction notes

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