Sodium Carbonate → HCID 59627653, compound

HRID 1930161Notes

Reaction equation

HRID 1930161 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].[F:21][C:22]1[CH:23]=[C:24]([CH:37]([CH3:42])[C:38]([O:40][CH3:41])=[O:39])[CH:25]=[C:26]([F:36])[C:27]=1OS(C(F)(F)F)(=O)=O.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:27]3[C:26]([F:36])=[CH:25][C:24]([CH:37]([CH3:42])[C:38]([O:40][CH3:41])=[O:39])=[CH:23][C:22]=3[F:21])=[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 59627637HCID 59627637, compound2×HCID 596277414-(6-Carbamoyl-3,5-dimethylpyrazin-2-yl)phenylboronic acid

Product 1

HCID 59627653HCID 59627653, compoundYield 67.6%

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 (175 mg, 0.65 mmol) and methyl 2-(3,5-difluoro-4-(trifluoromethylsulfonyloxy)phenyl)propanoate (Intermediate 21-2; 200 mg, 0.57 mmol) and Sodium carbonate (0.467 mL, 0.93 mmol), tetrakis(triphenylphosphine)palladium(0) (41.1 mg, 0.04 mmol) and lithium chloride (42.6 mg, 1.01 mmol) in DME (14.300 mL) was degassed and then stirred at 85° C. for 17 hours. The reaction mixture was partitioned between EtOAc (10 mL) and saturated brine (15 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)-2,6-difluorobiphenyl-4-yl)propanoate (164 mg, 67.1%) as a white solid.

Workup

  1. customThe reaction mixture was partitioned between EtOAc (10 mL) and saturated brine (15 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customto afford crude product
  6. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in isohexane
  7. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-d78c107465614ad0aaed448ddab93a9d
Source dataset
uspto-grants-2012_05
Patent number
US08188092B2

Reaction notes

Loading…