Dichloromethane → Ethyl 5-amino-6-(4-(tert-butoxycarbonyl)-3-fluorophenyl)pyrazine-2-carboxylate

HRID 596124Notes

Reaction equation

HRID 596124 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[N:6][C:7]=1Br.[F:14][C:15]1[CH:27]=[C:26](B2OC(C)(C)C(C)(C)O2)[CH:25]=[CH:24][C:16]=1[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.CCOC(C)=O.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]>[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[N:6][C:7]=1[C:26]1[CH:25]=[CH:24][C:16]([C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])=[C:15]([F:14])[CH:27]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 75486460tert-Butyl 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoateHCID 118045269Ethyl 5-amino-6-bromopyrazine-2-carboxylate

Product 1

HCID 118045523Ethyl 5-amino-6-(4-(tert-butoxycarbonyl)-3-fluorophenyl)pyrazine-2-carboxylateYield 74%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of ethyl 5-amino-6-bromopyrazine-2-carboxylate (210 mg, 0.853 mmol), tert-butyl 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (357 mg, 1.109 mmol), PdCl2(dppf).CH2Cl2 adduct (69.7 mg, 0.085 mmol) and Na2CO3 (362 mg, 3.41 mmol) (2M solution was used) in DME (5 mL) was placed into a 20 ml vial and sealed. The mixture was microwaved for 15 min at 110° C. The mixture was diluted with EtOAc, washed with water twice and brine, dried, filtered, and concentrated to afford the crude as a light yellow solid. The crude product was purified by ISCO (12 g, 10-55% EtOAc in heptane, 30 min) to afford 228 mg (74% yield) of light yellow solid. LC-MS (m/z): 362.1 (MH+), 0.89 min.

Workup

  1. customsealed
  2. customThe mixture was microwaved for 15 min at 110° C
  3. washwashed with water twice
  4. dry with materialbrine, dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford the crude as a light yellow solid
  8. customThe crude product was purified by ISCO (12 g, 10-55% EtOAc in heptane, 30 min)
  9. customto afford 228 mg (74% yield) of light yellow solid
  10. custom362.1 (MH+), 0.89 min.

Sources & evidence

ORD record
ord-5d738a43e1c7443b9811dbd777934ac7
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

Loading…