Ethyl Acetate → 1-(3-Chloro-4-methoxyphenyl)-4-fluoro-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-3-amine

HRID 1662196Notes

Reaction equation

HRID 1662196 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([Cl: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:28]1[CH:33]=[C:32](B(O)O)[CH:31]=[N:30][CH:29]=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>[Cl: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][C:22]=1[O:25][CH3:26]

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 585795311-(3-Bromophenyl)-1-(3-chloro-4-methoxyphenyl)-4-fluoro-1H-isoindol-3-amine

Product 1

HCID 585795171-(3-Chloro-4-methoxyphenyl)-4-fluoro-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-3-amineYield 37.2%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 57417360Sodium chloride; waterSolventHCID 86587095Dimethoxyethane ethanol waterSolvent

Procedure

1-(3-Bromophenyl)-1-(3-chloro-4-methoxyphenyl)-4-fluoro-1H-isoindol-3-amine (570 mg, 1.28 mmol), pyrimidin-5-ylboronic acid (190 mg, 1.53 mmol), cesium carbonate (1250 mg, 3.84 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (104 mg, 0.13 mmol) were dissolved in DME:EtOH:Water (6:3:1) (5 mL) and irradiated in a microwave oven for 20 min at 150° C. EtOAc, water and brine were added. The organic phase was collected, dried, filtered and then the solvent was removed under reduced pressure. The residue was purified by preparative HPLC to give 212 mg (37%) of the title product. MS (ES+) m/z 445 [M+1]+.

Workup

  1. customirradiated in a microwave oven for 20 min at 150° C
  2. customThe organic phase was collected
  3. customdried
  4. filtrationfiltered
  5. customthe solvent was removed under reduced pressure
  6. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-ab04555ef1894961903dd62c7cd7989c
Source dataset
uspto-grants-2011_10
Patent number
US08030500B2

Reaction notes

Loading…