Dichloromethane → Methyl 4-(3-aminopyrazin-2-yl)-2-fluorobenzoate

HRID 595988Notes

Reaction equation

HRID 595988 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].C(Cl)Cl>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]>[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

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 2762242-Amino-3-chloropyrazineHCID 221715283-Fluoro-4-methoxycarbonylphenylboronic acid, pinacol ester

Product 1

HCID 118045820Methyl 4-(3-aminopyrazin-2-yl)-2-fluorobenzoateYield 84%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

To 3-chloropyrazin-2-amine (27 g, 208 mmol) in DME (391 mL) and sodium carbonate (66.3 g, 625 mmol) was added methyl 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (64.2 g, 229 mmol) and PdCl2(dppf).CH2Cl2 adduct (8.51 g, 10.42 mmol). The reaction mixture was purged with N2 and heated in oil bath at 100° C. for 3h. The reaction mixture was partitioned between EtOAc and water. The organic layer was separated, washed with brine, dried over sodium sulfate, filtered and evaporated. The crude product was recrystallized by EtOAc and heptane (2:3) to give methyl 4-(3-aminopyrazin-2-yl)-2-fluorobenzoate in 84% yield. LCMS (m/z): 248.1 (MH+), 0.58 min.

Workup

  1. customThe reaction mixture was purged with N2
  2. customThe reaction mixture was partitioned between EtOAc 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 product was recrystallized by EtOAc and heptane (2:3)

Sources & evidence

ORD record
ord-3c8108b0520048ff9cc01e0f663f045b
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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