Methanol → HCID 46203075, compound

HRID 1662270Notes

Reaction equation

HRID 1662270 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:10]2([C:21]3[CH:26]=[CH:25][N:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=3)[C:18]3[C:13](=[C:14]([F:19])[CH:15]=[CH:16][CH:17]=3)[C:12]([NH2:20])=[N:11]2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[N:31]1[CH:36]=[C:35](B(O)O)[CH:34]=[N:33][CH:32]=1.C(=O)([O-])[O-].[K+].[K+].CO>CN(C=O)C.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]>[F:19][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]2[C:13]=1[C:12]([NH2:20])=[N:11][C:10]2([C:4]1[CH:5]=[CH:6][C:7]([O:8][CH3:9])=[C:2]([C:35]2[CH:36]=[N:31][CH:32]=[N:33][CH:34]=2)[CH:3]=1)[C:21]1[CH:26]=[CH:25][N:24]=[C:23]([C:27]([F:28])([F:29])[F:30])[CH:22]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 11430Potassium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 58579532HCID 58579532, compound

Product 1

HCID 46203075HCID 46203075, compoundYield 43.3%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

1-(3-Bromo-4-methoxyphenyl)-4-fluoro-1-(2-(trifluoromethyl)pyridin-4-yl)-1H-isoindol-3-amine (1.5 g, 3.12 mmol), pyrimidin-5-ylboronic acid (0.542 g, 4.37 mmol), [1,1′-bis (diphenylphosphino)ferrocene]palladium(II) chloride (0.128 g, 0.16 mmol) and aqueous potassium carbonate (2M, 4.69 mL, 9.37 mmol) were dissolved in DMF (14 mL). The resulting mixture was heated to 150° C. for 20 mins by microwaves. Methanol (20 mL) was added and the mixture concentrated in vacuo. Dichloromethane (40 mL), water (20 mL) and brine (5 mL) were added and the organic phase separated and evaporated directly on silica. The crude product was purified by gradient column chromatography (40 g silica column eluted with 0-10% [0.1M ammonia in methanol] in dichloromethane). The desired fractions were combined and evaporated to give 648 mg (43%) of the title compound.

Workup

  1. concentrationthe mixture concentrated in vacuo
  2. additionDichloromethane (40 mL), water (20 mL) and brine (5 mL) were added
  3. customthe organic phase separated
  4. customevaporated directly on silica
  5. customThe crude product was purified by gradient column chromatography (40 g silica column eluted with 0-10% [0.1M ammonia in methanol] in dichloromethane)
  6. customevaporated

Sources & evidence

ORD record
ord-234729235199446189614b145aa6713a
Source dataset
uspto-grants-2011_10
Patent number
US08030500B2

Reaction notes

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