Ethanol → HCID 136160552, compound

HRID 1930131Notes

Reaction equation

HRID 1930131 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([NH2:10])=[O:9])[C:5]([CH3:11])=[N:4][C:3]=1[CH3:12].[F:13][C:14]1[CH:19]=[C:18](B2OC(C)(C)C(C)(C)O2)[CH:17]=[CH:16][C:15]=1[OH:29].P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(O)C>COCCOC.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].C(Cl)Cl.O>[F:13][C:14]1[CH:19]=[C:18]([C:2]2[N:7]=[C:6]([C:8]([NH2:10])=[O:9])[C:5]([CH3:11])=[N:4][C:3]=2[CH3:12])[CH:17]=[CH:16][C:15]=1[OH:29]

Participants

8

Reactant 4

HCID 702EthanolHCID 62657Potassium Phosphate, TribasicHCID 115722382-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol2×HCID 57992034HCID 57992034, compound2×

Product 1

HCID 136160552HCID 136160552, compoundYield 69.6%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 6-chloro-3,5-dimethylpyrazine-2-carboxamide (Intermediate A) (492 mg, 2.65 mmol) and 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (Intermediate 6-6; 630 mg, 2.65 mmol) and potassium phosphate, tri-basic (674 mg, 3.18 mmol) in DME (10 mL), ethanol (5 mL) and water (2.5 mL) was thoughroughly degassed. The mixture was treated with PdCl2(dppf)-DCM adduct (108 mg, 0.13 mmol), degassed again and the atmosphere replaced with nitrogen before being heated to 80° C. for 4 hours. The reaction mixture was allowed to cool to room temperature and then evaporated. The crude product was partitioned between EtOAc (75 mL), and 1N citric acid (25 mL) and the precipitate was collected by filtration, washed with water (10 mL) and air dried to afford 6-(3-fluoro-4-hydroxyphenyl)-3,5-dimethylpyrazine-2-carboxamide (481 mg, 69.6%) as a beige solid, which was used without further purification.

Workup

  1. customdegassed again
  2. temperatureto cool to room temperature
  3. customevaporated
  4. customThe crude product was partitioned between EtOAc (75 mL), and 1N citric acid (25 mL)
  5. filtrationthe precipitate was collected by filtration
  6. washwashed with water (10 mL) and air
  7. customdried

Sources & evidence

ORD record
ord-660d910e16e3499a8853834e3d672b13
Source dataset
uspto-grants-2012_05
Patent number
US08188092B2

Reaction notes

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