Cesium carbonate → 1-(2-(Difluoromethyl)pyridin-4-yl)-4-fluoro-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-3-amine

HRID 1662260Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([C:8]2([C:19]3[CH:24]=[CH:23][N:22]=[C:21]([CH:25]([F:27])[F:26])[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:5]=[CH:6][CH:7]=1.[N:28]1[CH:33]=[C:32](B(O)O)[CH:31]=[N:30][CH:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>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].COCCOC.CCO.O>[F:26][CH:25]([F:27])[C:21]1[CH:20]=[C:19]([C:8]2([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([C:32]4[CH:33]=[N:28][CH:29]=[N:30][CH:31]=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]=[CH:23][N:22]=1

Participants

Conditions

Temperature: 150 °C

Procedure

1-(3-Bromophenyl)-1-(2-(difluoromethyl)pyridin-4-yl)-4-fluoro-1H-isoindol-3-amine (0.168 g, 0.39 mmol), 5-pyrimidinylboronic acid (0.063 g, 0.51 mmol), [1,1′-bis (diphenylphosphino)ferrocene]palladium(II) chloride (0.016 g, 0.02 mmol), cesium carbonate (0.093 mL, 1.17 mmol) and DME:EtOH:water (6:3:1) (10.0 mL) were added to a microwave vial and heated at 150° C. in a microwave reactor for 20 min. Additional 5-pyrimidinylboronic acid (0.048 g, 0.39 mmol) was added. The reaction mixture was heated at 150° C. in a microwave reactor for 20 min. The reaction mixture was filtered through a syringe filter, concentrated in vacuo, redissolved in methanol and purified by preparative HPLC to afford the title compound (0.115 g, 60%).

Workup

temperatureThe reaction mixture was heated at 150° C. in a microwave reactor for 20 min
filtrationThe reaction mixture was filtered through a syringe
filtrationfilter
concentrationconcentrated in vacuo
dissolutionredissolved in methanol
custompurified by preparative HPLC

Sources & evidence

ORD record: ord-7a3cb134281845038b120b3544c8576e
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08030500B2

Reaction notes

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