Dimethylformamide → 4-Fluoro-1-(2-fluoro-5-(pyrimidin-5-yl)phenyl)-1-(2-methylpyridin-4-yl)-1H-isoindol-3-amine

HRID 1662225Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]([F:26])=[C:6]([C:8]2([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([CH3:25])[CH: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:7]=1.[N:27]1[CH:32]=[C:31](B(O)O)[CH:30]=[N:29][CH:28]=1.C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>[Cl-].[Na+].O.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe]>[F:17][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[C:11]=1[C:10]([NH2:18])=[N:9][C:8]2([C:6]1[CH:7]=[C:2]([C:31]2[CH:32]=[N:27][CH:28]=[N:29][CH:30]=2)[CH:3]=[CH:4][C:5]=1[F:26])[C:19]1[CH:24]=[CH:23][N:22]=[C:21]([CH3:25])[CH:20]=1

Participants

Conditions

Temperature: 150 °C

Procedure

1-(5-Bromo-2-fluorophenyl)-4-fluoro-1-(2-methylpyridin-4-yl)-1H-isoindol-3-amine (80 mg, 0.19 mmol), 5-pyrimidinylboronic acid (31.1 mg, 0.25 mmol), [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (15.77 mg, 0.02 mmol), potassium carbonate (2.5 M, aq, 0.290 mL, 0.58 mmol) and DMF (2 mL) were added to a vial and heated in a microwave reactor at 150° C. for 15 min. Brine was added and the product mixture was extracted EtOAc. The organic phase was dried (Na2SO4), filtered and concentrated in vacuo. Purification by preparative HPLC afforded 34.0 mg (43% yield) of the title compound.

Workup

extractionthe product mixture was extracted EtOAc
dry with materialThe organic phase was dried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customPurification by preparative HPLC

Sources & evidence

ORD record: ord-b57761e9d39146669859980376aeba9b
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08030500B2

Reaction notes

Loading…