Cesium carbonate → (5-(3-Amino-4-fluoro-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-1-yl)-2-methoxy-3-methylphenyl)methanol

HRID 1662201Notes

Reaction equation

HRID 1662201 reaction equation
[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[F:11])[C:4]([C:19]2[CH:20]=[C:21]([CH3:29])[C:22]([O:27][CH3:28])=[C:23]([CH2:25][OH:26])[CH:24]=2)([C:12]2[CH:17]=[CH:16][CH:15]=[C:14](Br)[CH:13]=2)[N:3]=1.[N:30]1[CH:35]=[C:34](B(O)O)[CH:33]=[N:32][CH:31]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.CCO.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]>[NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[F:11])[C:4]([C:19]2[CH:20]=[C:21]([CH3:29])[C:22]([O:27][CH3:28])=[C:23]([CH2:25][OH:26])[CH:24]=2)([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:34]3[CH:35]=[N:30][CH:31]=[N:32][CH:33]=3)[CH:13]=2)[N:3]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 58579488(5-(3-Amino-1-(3-bromophenyl)-4-fluoro-1H-isoindol-1-yl)-2-methoxy-3-methylphenyl)methanol

Product 1

HCID 58579497(5-(3-Amino-4-fluoro-1-(3-(pyrimidin-5-yl)phenyl)-1H-isoindol-1-yl)-2-methoxy-3-methylphenyl)methanolYield 74.3%

Reagents, catalysts & solvents 2

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

Procedure

(5-(3-Amino-1-(3-bromophenyl)-4-fluoro-1H-isoindol-1-yl)-2-methoxy-3-methylphenyl)methanol (338 mg, 0.74 mmol), pyrimidine-5-boronic acid (110 mg, 0.89 mmol), cesium carbonate (726 mg, 2.23 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (60.6 mg, 0.07 mmol) were dissolved in DME:EtOH:water (6:3:1) (5 mL) and irradiated in a microwave oven for 20 min at 150° C. The solvent was evaporated in vacuo and to the residue was added water, 2 M HCl solution to reach pH˜7, and EtOAc. The organic phase was collected, dried and filtered. The solvent was removed under reduced pressure and the residue was purified by preparative HPLC to give 250 mg (74%) of the title compound.

Workup

  1. customirradiated in a microwave oven for 20 min at 150° C
  2. customThe solvent was evaporated in vacuo and to the residue
  3. additionwas added water, 2 M HCl solution
  4. customThe organic phase was collected
  5. customdried
  6. filtrationfiltered
  7. customThe solvent was removed under reduced pressure
  8. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-0d854741bca347e5980e91958ca2c20d
Source dataset
uspto-grants-2011_10
Patent number
US08030500B2

Reaction notes

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