Sodium Carbonate → 6-(Quinoxalin-6-yl)-N-(4-(trifluoromethyl)phenyl)pyrimidin-4-amine

HRID 2249713Notes

Reaction equation

HRID 2249713 reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=2)[CH:3]=1.Cl.[N:20]1[C:25]2[CH:26]=[CH:27][C:28](B(O)O)=[CH:29][C:24]=2[N:23]=[CH:22][CH:21]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[N:20]1[C:25]2[C:24](=[CH:29][C:28]([C:2]3[N:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]4[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=4)[CH:3]=3)=[CH:27][CH:26]=2)[N:23]=[CH:22][CH:21]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 45073595Quinoxalin-6-ylboronic acid hydrochlorideHCID 467399256-chloro-N-(4-(trifluoromethyl)phenyl)pyrimidin-4-amine

Product 1

HCID 112571286-(Quinoxalin-6-yl)-N-(4-(trifluoromethyl)phenyl)pyrimidin-4-amine

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 6-chloro-N-(4-(trifluoromethyl)phenyl)pyrimidin-4-amine (273 mg, 1.0 mmol), benzopyrazine-6-boronic acid hydrochloride (Asymchem, 211 mg, 1.0 mmol), Na2CO3 (529 mg, 5.0 mmol) and PdCl2(PPh3)2 (Strem, 60 mg, 0.1 mmol) in 7 mL DME/3 mL H2O/2 mL EtOH was heated to 120° C. for 17 min in the Smith Optimizer microwave. The reaction mixture was partitioned between EtOAc/brine and the aqueous layer was extracted with EtOAc (3×). The combined organics were evaporated onto SiO2 and purified by flash column chromatography eluting with EtOAc/Hexane/2M NH3 in MeOH/CH2Cl2 (0:1:0:0→1:1:0:0→0:0:19:1). The fractions containing desired compound were combined and concentrated in vacuo giving a solid. The solid was washed with a minimal amount of CH2Cl2 and dried in vacuo to give a light pink amorphous solid. MS (ESI, pos ion.) m/z: 368 (M+1).

Workup

  1. customThe reaction mixture was partitioned between EtOAc/brine
  2. extractionthe aqueous layer was extracted with EtOAc (3×)
  3. customThe combined organics were evaporated onto SiO2
  4. custompurified by flash column chromatography
  5. washeluting with EtOAc/Hexane/2M NH3 in MeOH/CH2Cl2 (0:1:0:0→1:1:0:0→0:0:19:1)
  6. additionThe fractions containing desired compound
  7. concentrationconcentrated in vacuo
  8. customgiving a solid
  9. washThe solid was washed with a minimal amount of CH2Cl2
  10. customdried in vacuo
  11. customto give a light pink amorphous solid

Sources & evidence

ORD record
ord-770fc082ddbc4ed9be1c676564cdafa2
Source dataset
uspto-grants-2008_01
Patent number
US07314933B2

Reaction notes

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