Sodium Carbonate → HCID 178432605, compound

HRID 635675Notes

Reaction equation

HRID 635675 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH3:8])[NH:5][C:4]2=[CH:9][C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[N:11][C:3]=12.[S:18]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(O)C.C1(C)C=CC=CC=1>[CH3:8][C:6]1[NH:5][C:4]2[C:3]([N:11]=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:9]=2)=[C:2]([C:20]2[CH:21]=[CH:22][S:18][CH:19]=2)[N:7]=1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 581760Thiophene-3-boronic acidHCID 178432852HCID 178432852, compound

Product 1

HCID 178432605HCID 178432605, compoundYield 73%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture of 4-chloro-2-methyl-6-phenylpyrrolo[3,2-d]pyrimidine (Example 1(e)) (50 mg, 0.21 mmol), thiophene-3-boronic acid (37 mg, 0.287 mmol), tris(dibenzylidene-acetone)dipalladium(0) (Aldrich Chemical Company) (4.7 mg, 0.0051 mmol, 0.025 eq) and triphenylphosphine (Aldrich Chemical Company) (10.8 mg, 0.041 mmol, 0.2 eq) in a mixed solvent (600 μL of toluene, 300 μL of 1.0 M Na2CO3, and 150 μL of ethanol) was heated at reflux under N2 for 17 h. Upon cooling to the room temperature, the reaction mixture was diluted with H2O (20 mL) and extracted with CHCl3 (3×20 mL). The organic phase was dried over Na2SO4, filtered and concentrated with a rotary evaporator. The crude material was purified by flash chromatography on silica gel a gradient eluant of EtOAc(0-25%):hexanes(100-75%) to afford 43.3 mg (73%) of an off-white solid. Mp: 232-233° C. 1H NMR (CDCl3; 400 MHz): δ 8.57 (s, 1), 8.04 (dd, 1, J=1.2, 2.9), 7.66 (m, 3), 7.59 (dd, 1, J=2.9, 5.0), 7.52 (t, 2, J=7.7), 7.46 (t, 1, J=7.7), 6.94 (d, 1, J=2.0), 2.86 (s, 3). MS m/z: 292 (M+1), 290 (M−1).

Workup

  1. temperaturewas heated
  2. temperatureat reflux under N2 for 17 h
  3. extractionextracted with CHCl3 (3×20 mL)
  4. dry with materialThe organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated with a rotary evaporator
  7. customThe crude material was purified by flash chromatography on silica gel a gradient eluant of EtOAc(0-25%)

Sources & evidence

ORD record
ord-950e161ef94d456fa9a2f25b0a1eead5
Source dataset
uspto-grants-2001_02
Patent number
US06187777B1

Reaction notes

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