Ethyl Acetate → 1-(2,6-Dimethylpyrimidin-4-yl)-4-fluoro-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-3-amine

HRID 1662264Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([C:8]2([C:19]3[CH:24]=[C:23]([CH3:25])[N:22]=[C:21]([CH3:26])[N:20]=3)[C:16]3[C:11](=[C:12]([F:17])[CH:13]=[CH:14][CH:15]=3)[C:10]([NH2:18])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.[N:27]1[CH:32]=[C:31](B(O)O)[CH:30]=[N:29][CH:28]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CCOC(C)=O>COCCOC.CCO.O.[Cl-].[Na+].O.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].O>[CH3:26][C:21]1[N:20]=[C:19]([C:8]2([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([C:31]4[CH:32]=[N:27][CH:28]=[N:29][CH:30]=4)[CH:3]=3)[C:16]3[C:11](=[C:12]([F:17])[CH:13]=[CH:14][CH:15]=3)[C:10]([NH2:18])=[N:9]2)[CH:24]=[C:23]([CH3:25])[N:22]=1

Participants

Conditions

Temperature: 150 °C

Procedure

1-(3-Bromophenyl)-1-(2,6-dimethylpyrimidin-4-yl)-4-fluoro-1H-isoindol-3-amine (300 mg, 0.73 mmol), pyrimidin-5-ylboronic acid (108 mg, 0.88 mmol), cesium carbonate (713 mg, 2.19 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (59.6 mg, 0.07 mmol) were dissolved in DME:EtOH:water (6:3:1) (5 mL) and heated in a microwave oven for 20 min at 150° C. EtOAc, water and brine were added and the organic phase was collected, dried and filtered. The solvent was removed under reduced pressure and the residue was purified by preparative HPLC to afford 49 mg (15%) of the title compound.

Workup

customthe organic phase was collected
customdried
filtrationfiltered
customThe solvent was removed under reduced pressure
customthe residue was purified by preparative HPLC

Sources & evidence

ORD record: ord-e5bd699261474cb4a7f9849b632f83e1
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08030500B2

Reaction notes

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