Sodium Carbonate → HCID 178432587, compound

HRID 1371130Notes

Reaction equation

HRID 1371130 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][CH:20]=[C:19]1B(O)O.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:19]2[S:18][CH:22]=[CH:21][CH:20]=2)[N:7]=1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 27339602-Thiopheneboronic acidHCID 178432852HCID 178432852, compound

Product 1

HCID 178432587HCID 178432587, compoundYield 62%

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-2-boronic acid (37 mg, 0.287 mmol), tris(dibenzylidene-acetone)dipalladium(0) (Aldrich Chemical Company) (4.7 mg, 0.0051 mmol) and triphenylphosphine (Aldrich Chemical Company) (10.8 mg, 0.041 mmol) in a mixed solvent (600 μL of toluene, 300 μL, 1.0 M Na2CO3 and 150 μL of ethanol) was heated at reflux under N2 for 36 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 with a gradient eluant of EtOAc(0-25%):hexanes(100-75%) to afford 37.2 mg (62%) of the title compound as a yellow solid. Mp: 178-179° C. 1H NMR (Acetone-d6; 400 MHz): δ 10.61 (s, 1), 8.21 (d, 1, J=4.5), 8.00 (d, 2, J=7.3), 7.73 (d, 2, J=4.5), 7.54 (t, 2, J=7.3), 7.48 (t, 1, J=7.3) 7.28 (t, 1, J=4.5), 6.96 (s, 1), 2.68 (s, 3). MS m/z: 292 (M+1), 290 (M−1). HRMS (NBA-NaI) m/z Calcd for M+H, C17H13N3S: 292.0908. Found: 292.0900.

Workup

  1. temperaturewas heated
  2. temperatureat reflux under N2 for 36 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 with a gradient eluant of EtOAc(0-25%)

Sources & evidence

ORD record
ord-4c8cda0a4244462b8505f8ee84b3acf2
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

Loading…