Sodium Carbonate → Methyl 2-(4'-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2,5-dichlorobiphenyl-4-yl)acetate

HRID 1930120Notes

Reaction equation

HRID 1930120 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].[Cl:21][C:22]1[CH:27]=[C:26](OS(C(F)(F)F)(=O)=O)[C:25]([Cl:36])=[CH:24][C:23]=1[CH2:37][C:38]([O:40][CH3:41])=[O:39].C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[Li+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([C:4]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:26]3[CH:27]=[C:22]([Cl:21])[C:23]([CH2:37][C:38]([O:40][CH3:41])=[O:39])=[CH:24][C:25]=3[Cl:36])=[CH:12][CH:11]=2)[C:7]([CH3:19])=[N:6][C:5]=1[CH3:20])(=[O:3])[NH2:2]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 59627706Methyl 2-(2,5-dichloro-4-(trifluoromethylsulfonyloxy)phenyl)acetate2×HCID 596277414-(6-Carbamoyl-3,5-dimethylpyrazin-2-yl)phenylboronic acid2×

Product 1

HCID 59627666Methyl 2-(4'-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2,5-dichlorobiphenyl-4-yl)acetateYield 32.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A solution of 4-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)phenylboronic acid (Intermediate 5-1; 312 mg, 1.15 mmol) and methyl 2-(2,5-dichloro-4-(trifluoromethylsulfonyloxy)phenyl)acetate (Intermediate 4-2; 375 mg, 1.02 mmol) and 2M sodium carbonate (0.830 mL, 1.66 mmol), tetrakis(triphenylphosphine)palladium(0) (73.2 mg, 0.06 mmol) and lithium chloride (76 mg, 1.79 mmol) in DME (10 mL) was degassed and then stirred at 85° C. for 17 hours. The reaction mixture was concentrated and diluted with EtOAc (75 mL), and washed sequentially with 2M HCl (25 mL) and saturated brine (25 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford methyl 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2,5-dichlorobiphenyl-4-yl)acetate (148 mg, 32.6%) as a yellow solid.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with EtOAc (75 mL)
  3. washwashed sequentially with 2M HCl (25 mL) and saturated brine (25 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto afford crude product
  8. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in isohexane
  9. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-0fe85a1304e747edb86947e7f033bb45
Source dataset
uspto-grants-2012_05
Patent number
US08188092B2

Reaction notes

Loading…