1,2-Dimethoxyethane → HCID 59627681, compound

HRID 1930145Notes

Reaction equation

HRID 1930145 reaction equation
[C:1]([C:4]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13](B(O)O)=[CH:12][CH:11]=2)[C:7]([CH3:19])=[N:6][C:5]=1[CH3:20])(=[O:3])[NH2:2].[CH3:21][C:22]1[CH:23]=[C:24]([CH2:36][C:37]([O:39][CH3:40])=[O:38])[CH:25]=[CH:26][C:27]=1OS(C(F)(F)F)(=O)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH3:49]OCCOC>C(O)C.O.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:1]([C:4]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:27]3[CH:26]=[CH:25][C:24]([CH2:36][C:37]([O:39][CH2:40][CH3:49])=[O:38])=[CH:23][C:22]=3[CH3:21])=[CH:12][CH:11]=2)[C:7]([CH3:19])=[N:6][C:5]=1[CH3:20])(=[O:3])[NH2:2]

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 62657Potassium Phosphate, TribasicHCID 59627642HCID 59627642, compound2×HCID 596277414-(6-Carbamoyl-3,5-dimethylpyrazin-2-yl)phenylboronic acid

Product 1

HCID 59627681HCID 59627681, compoundYield 38.4%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)phenylboronic acid (138 mg, 0.51 mmol), methyl 2-(3-methyl-4-(trifluoromethylsulfonyloxy)phenyl)acetate (Intermediate 12-2; 159 mg, 0.51 mmol) and tripotassium phosphate (162 mg, 0.76 mmol) in DME (3 mL), ethanol (1.5 mL) and water (0.5 mL) was degassed before addition of (1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) (DCM adduct) (33.5 mg, 0.04 mmol). The reaction mixture was heated to 80° C., under nitrogen, and left to stir overnight for 16 hrs. The reaction mixture was allowed to cool to room temperature and then evaporated. The residue was partitioned between water (20 mL) and EtOAc (50 mL). The aqueous was re-extracted with EtOAc (2×10 mL) and the combined organics washed with brine (20 mL), dried (MgSO4) and evaporated to give crude product. The crude product was purified by flash silica chromatography, elution gradient 10 to 100% EtOAc in isohexane on 12 g silicycle column. Pure fractions were evaporated to dryness to afford ethyl 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-methylbiphenyl-4-yl)acetate (79 mg, 38.4%) as a colourless oil which crystallised on standing.

Workup

  1. waitleft
  2. temperatureto cool to room temperature
  3. customevaporated
  4. customThe residue was partitioned between water (20 mL) and EtOAc (50 mL)
  5. extractionThe aqueous was re-extracted with EtOAc (2×10 mL)
  6. washthe combined organics washed with brine (20 mL)
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customto give crude product
  10. customThe crude product was purified by flash silica chromatography, elution gradient 10 to 100% EtOAc in isohexane on 12 g silicycle column
  11. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-97a66bb901724bfe9029fcdce95bd2f1
Source dataset
uspto-grants-2012_05
Patent number
US08188092B2

Reaction notes

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