Sodium Carbonate → Methyl 4-(3-aminopyrazin-2-yl)-2-fluorobenzoate

HRID 596087Notes

Reaction equation

HRID 596087 reaction equation
Cl[C:2]1[C:3]([NH2:8])=[N:4][CH:5]=[CH:6][N:7]=1.C(=O)([O-])[O-].[Na+].[Na+].[F:15][C:16]1[CH:25]=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:23]=[CH:22][C:17]=1[C:18]([O:20][CH3:21])=[O:19]>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>[NH2:8][C:3]1[C:2]([C:24]2[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[C:16]([F:15])[CH:25]=2)=[N:7][CH:6]=[CH:5][N:4]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2762242-Amino-3-chloropyrazineHCID 221715283-Fluoro-4-methoxycarbonylphenylboronic acid, pinacol ester

Product 1

HCID 118045820Methyl 4-(3-aminopyrazin-2-yl)-2-fluorobenzoateYield 111.1%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 3-chloropyrazin-2-amine (5 g, 38.6 mmol) in DME (160 mL) and aq. 2 M sodium carbonate (40 mL, 80 mmol) was added methyl 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (12.97 g, 46.3 mmol) followed by PdCl2(dppf)-CH2Cl2 adduct (3.15 g, 3.86 mmol). The reaction mixture was purged with N2 and heated in an oil bath at 100° C. for 3-4 h. The reaction mixture was partitioned between ethylacetate and water. The organic layer was separated, washed with brine, dried over sodium sulfate, filtered and evaporated. The crude was triturated with DCM. Solid observed was filtered, washed with ether and dried under reduced pressure to provide product as an off white solid. Filtrate was purified by flash chromatography eluting with 0-50-80% EtOAc/heptane to provide 10.6 g of product in 93% yield. LCMS (m/z): 248.1 (MH+), 0.563 min.

Workup

  1. customThe reaction mixture was purged with N2
  2. customThe reaction mixture was partitioned between ethylacetate and water
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude was triturated with DCM
  9. filtrationSolid observed was filtered
  10. washwashed with ether
  11. customdried under reduced pressure
  12. customto provide product as an off white solid
  13. customFiltrate was purified by flash chromatography
  14. washeluting with 0-50-80% EtOAc/heptane

Sources & evidence

ORD record
ord-80f8d6ffad4f497d9efd08d49c5d3705
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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