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

HRID 220134

Reaction equation

HRID 220134 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-b92ca4da2c9f4ce8b2b03dbf65bb7fd1
Source dataset
uspto-grants-2012_06
Patent number
US08202883B2

Linked notes

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