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

HRID 1662261Notes

Reaction equation

Br[C:2]1[CH:7]=[C:6]([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:4][N:3]=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:6]3[CH:5]=[CH:4][N:3]=[C:2]([C:32]4[CH:33]=[N:28][CH:29]=[N:30][CH:31]=4)[CH:7]=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-(2-Bromopyridin-4-yl)-1-(2-(difluoromethyl)pyridin-4-yl)-4-fluoro-1H-isoindol-3-amine (64 mg, 0.15 mmol), 5-pyrimidinylboronic acid (23.80 mg, 0.19 mmol), [1,1′-bis (diphenylphosphino)ferrocene]palladium(II) chloride (6.03 mg, 7.39 μmol), cesium carbonate (0.035 mL, 0.44 mmol) and DME:EtOH:water (6:3:1) (3.00 mL) were put in a microwave vial and heated at 150° C. in a microwave reactor for 20 min. The reaction mixture was filtered through a syringe filter and purified by prep-HPLC. The desired fractions were pooled and freeze dried over night to give the title compound (25.7 mg, 39%).

Workup

filtrationThe reaction mixture was filtered through a syringe
filtrationfilter
custompurified by prep-HPLC
customfreeze dried over night

Sources & evidence

ORD record: ord-fc951f805751437a86c026d3357e0bac
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08030500B2

Reaction notes

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