Tricyclohexylphosphine → 4-[4'-(Ethylsulfonyl)-6-fluorobiphenyl-3-yl]-7-(propan-2-yl)-7H-imidazo[4,5-c]pyridazine

HRID 1845987Notes

Reaction equation

[CH2:1]([S:3]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:17]([F:18])=[CH:16][CH:15]=[C:14](B(O)O)[CH:13]=2)=[CH:8][CH:7]=1)(=[O:5])=[O:4])[CH3:2].Cl[C:23]1[C:24]2[N:31]=[CH:30][N:29]([CH:32]([CH3:34])[CH3:33])[C:25]=2[N:26]=[N:27][CH:28]=1.P([O-])([O-])[O-].[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>O1CCOCC1.O>[CH2:1]([S:3]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:17]([F:18])=[CH:16][CH:15]=[C:14]([C:23]3[C:24]4[N:31]=[CH:30][N:29]([CH:32]([CH3:34])[CH3:33])[C:25]=4[N:26]=[N:27][CH:28]=3)[CH:13]=2)=[CH:8][CH:7]=1)(=[O:5])=[O:4])[CH3:2]

Participants

Conditions

Temperature: 100 °C

Procedure

A stirred solution of 4′-ethylsulfonyl-6-fluorobiphenyl-3-yl-boronic acid (Preparation 65, 30 mg, 0.097 mmol), 4-chloro-7-isopropyl-7H-imidazo[4,5-c]pyridazine (Preparation 6, 15 mg, 0.077 mmol) and potassium phosphite (33 mg, 0.154 mmol) in dioxane (3 mL) and water (0.7 mL) was degassed with argon for 10 minutes followed by the addition of tricyclohexylphosphine (1.72 mg, 0.006 mmol) and tris(dibenzylideneacetone)palladium(0) (2.82 mg, 0.003 mmol). The resulting mixture was heated at 100° C. for 16 hours. The reaction mixture was filtered to remove inorganics and the filtrate was concentrated in vacuo to remove the volatiles. Purification of the crude residue by preparative TLC eluting with 2% MeOH in DCM afforded the title compound as off white solid in 27% yield, 9 mg.

Workup

filtrationThe reaction mixture was filtered
customto remove inorganics
concentrationthe filtrate was concentrated in vacuo
customto remove the volatiles
customPurification of the crude residue by preparative TLC
washeluting with 2% MeOH in DCM

Sources & evidence

ORD record: ord-53b8cb4a168b4f01accf7de5ad725fa9
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08952008B2

Reaction notes

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