Sodium Carbonate → 1-(2-(Difluoromethyl)-6-methylpyridin-4-yl)-4-fluoro-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-3-amine

HRID 1662253Notes

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]([CH:26]([F:28])[F:27])[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:29]1[CH:34]=[C:33](B(O)O)[CH:32]=[N:31][CH:30]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[F:27][CH:26]([F:28])[C:21]1[CH:20]=[C:19]([C:8]2([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([C:33]4[CH:34]=[N:29][CH:30]=[N:31][CH:32]=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: 140 °C

Procedure

1-(3-Bromophenyl)-1-(2-(difluoromethyl)-6-methylpyridin-4-yl)-4-fluoro-1H-isoindol-3-amine (40 mg, 0.09 mmol), pyrimidin-5-ylboronic acid (12.22 mg, 0.10 mmol) and (1,1′-bis (diphenylphosphino)ferrocene)-dichloropalladium(II) (7.37 mg, 8.96 μmol) were mixed in THF (3 mL). Aqueous sodium carbonate (2M) (0.134 mL, 0.27 mmol) was added and the mixture was heated in a microwave reactor for 40 min at 140° C. The mixture was filtered through a pad of Celite®, eluated with DCM (15 mL) and concentrated in vacuo. Purification by preparative HPLC afforded 11.0 mg (27%) of the title compound.

Workup

filtrationThe mixture was filtered through a pad of Celite®
concentrationconcentrated in vacuo
customPurification by preparative HPLC

Sources & evidence

ORD record: ord-1b8e182516784d54af49071696c888f7
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08030500B2

Reaction notes

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