Sodium Carbonate → 4-(3-Amino-pyrido[2,3-b]pyrazin-6-yl)-2-methoxy-phenol

HRID 43250

Reaction equation

HRID 43250 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[C:6]([N:12]=1)=[N:7][C:8]([NH2:11])=[CH:9][N:10]=2.[CH3:13][O:14][C:15]1[CH:20]=[C:19](B2OC(C)(C)C(C)(C)O2)[CH:18]=[CH:17][C:16]=1[OH:30].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.FC1(F)C(F)(C(F)(F)F)C(F)(F)C(F)(F)C(F)(F)C1(F)F>[NH2:11][C:8]1[N:7]=[C:6]2[N:12]=[C:2]([C:19]3[CH:18]=[CH:17][C:16]([OH:30])=[C:15]([O:14][CH3:13])[CH:20]=3)[CH:3]=[CH:4][C:5]2=[N:10][CH:9]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27346502-Methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol2×HCID 866355376-Chloro-pyrido[2,3-b]pyrazin-3-ylamine

Product 1

HCID 1361664224-(3-Amino-pyrido[2,3-b]pyrazin-6-yl)-2-methoxy-phenolYield 94.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 9637Perfluoro(methylcyclohexane)Solvent

Conditions

Temperature
75 °C

Procedure

To a suspension of 1.13 g 6-Chloro-pyrido[2,3-b]pyrazin-3-ylamine (5.94 mmol; 1 eq) and 1.67 g 2-Methoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenol (6.55 mmol; 1.1 eq.) in ethylene glycol dimethyl ether (45 mL) under Ar, a solution of 6.29 g sodium carbonate (59.3 mmol; 10 eq.) in water (20 mL) and a suspension of 378 mg FluoroFlash catalyst (0.24 mmol; 0.04 eq.) in undecafluoro(trifluoromethyl)cyclohexane (45 mL) were added. The mixture was heated to 75° C. for 5 hours. Additional 0.76 g (2.97 mmol; 0.5 eq) of 2-Methoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenol were added and the resulting mixture was stirred at 75° C. for 7.5 hours. After cooling to room temperature, the aqueous and organic phase were separated from the fluorous phase and concentrated in vacuo. The residue was dissolved in methanol and methylene dichloride and filtered. The black solution was again concentrated in vacuo. The residue was taken up in water and the resulting solution was neutralized with 1 N HCl whereas the product crystallizes. The brown solid was filtered of, washed with water and dried in vacuo to afford 1.5 g (80.2% yield) of 4-(3-Amino-pyrido[2,3-b]pyrazin-6-yl)-2-methoxy-phenol.

Workup

  1. additionwere added
  2. temperatureAfter cooling to room temperature
  3. customthe aqueous and organic phase were separated from the fluorous phase
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in methanol
  6. filtrationmethylene dichloride and filtered
  7. concentrationThe black solution was again concentrated in vacuo
  8. customcrystallizes
  9. filtrationThe brown solid was filtered of,
  10. washwashed with water
  11. customdried in vacuo

Sources & evidence

ORD record
ord-6d175a88e4d84227bd76dce4e95f35c9
Source dataset
uspto-grants-2013_09
Patent number
US08536332B2

Linked notes

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