Potassium Carbonate → 2-Fluoro-5-(6-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazin-3-yl)benzonitrile

HRID 869135Notes

Reaction equation

Cl[C:2]1[N:7]=[N:6][C:5]([NH:8][CH2:9][C:10]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)([CH3:12])[CH3:11])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[C:26]([C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][C:33]=1[F:34])#[N:27]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:34][C:33]1[CH:32]=[CH:31][C:30]([C:2]2[N:7]=[N:6][C:5]([NH:8][CH2:9][C:10]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)([CH3:12])[CH3:11])=[CH:4][CH:3]=2)=[CH:29][C:28]=1[C:26]#[N:27]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 6-chloro-N-(2-(4-fluorophenyl)-2-methylpropyl)pyridazin-3-amine (5.0 g, 23 mmol, 1.0 equiv) and K2CO3 (9.4 g, 68 mmol, 3.0 equiv) in dioxane (35 mL) was added Pd(dppf)Cl2 (1.7 g, 2.3 mmol, 0.1 equiv) and 3-cyano-4-fluorophenylboronic acid (5.0 g, 30 mmol, 1.3 equiv). The mixture was stirred at 80° C. for 3 hours after which it was allowed to cool to room temperature and concentrated in vacuo. The residue was diluted with EtOAc, washed with saturated NaHCO3, dried over Na2SO4 and evaporated to dryness. The residue was purified by reverse phase HPLC using a CH3CN/water gradient to give the desired product (5.3 g, 63%).

Workup

temperatureto cool to room temperature
concentrationconcentrated in vacuo
additionThe residue was diluted with EtOAc
washwashed with saturated NaHCO3
dry with materialdried over Na2SO4
customevaporated to dryness
customThe residue was purified by reverse phase HPLC

Sources & evidence

ORD record: ord-82843fa5972f469e8e4de3e70db4038e
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969346B2

Reaction notes

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