Potassium Carbonate → 6-(1-Methylisoquinolin-4-yloxy)nicotinonitrile

HRID 2060856Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[CH:15][N:14]=2)=[CH:4][N:3]=1.[CH3:21]B1OB(C)OB(C)O1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH3:21][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][C:13]2[CH:20]=[CH:19][C:16]([C:17]#[N:18])=[CH:15][N:14]=2)=[CH:4][N:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 6-(1-chloroisoquinolin-4-yloxy)nicotinonitrile (Preparation 17) (300 mg, 1.1 mmol) in DMF (8 mL) under argon was added trimethylboroxine (148 μL, 1.1 mmol) followed by K2CO3 (442 mg, 3.2 mmol) and palladium tetrakistriphenylphosphine (123 mg, 0.1 mmol). The mixture was purged with argon for 5 min and then heated to 80° C. for 16 h. Solvent was removed in vacuo. The residue was partitioned between EtOAc (100 mL) and water (40 mL), the organic phase was washed with water (40 mL), NaHCO3 (40 mL), brine (30 mL) and dried (MgSO4). Solvent was removed in vacuo and the residue purified by column chromatography (2% MeOH: DCM) to give the title compound: RT=2.40 min; m/z (ES+)=262.4 [M+H]+.

Workup

customThe mixture was purged with argon for 5 min
customSolvent was removed in vacuo
customThe residue was partitioned between EtOAc (100 mL) and water (40 mL)
washthe organic phase was washed with water (40 mL), NaHCO3 (40 mL), brine (30 mL)
dry with materialdried (MgSO4)
customSolvent was removed in vacuo
customthe residue purified by column chromatography (2% MeOH: DCM)

Sources & evidence

ORD record: ord-61ff624063f54ad3a618cb99ab98a386
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08278442B2

Reaction notes

Loading…