Sodium Carbonate → HCID 178488971, compound

HRID 1371129Notes

Reaction equation

HRID 1371129 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.[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>O.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(O)C.C1(C)C=CC=CC=1>[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([C:2]2[N:7]=[C:6]([CH3:8])[NH:5][C:4]3=[CH:9][C:10]([C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=4)=[N:11][C:3]=23)=[CH:22][CH:21]=1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 201262(4-Methoxyphenyl)boronic acidHCID 178432852HCID 178432852, compound

Product 1

HCID 178488971HCID 178488971, compoundYield 89%

Reagents, catalysts & solvents 4

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 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), 4-methoxyphenylboronic acid (Aldrich Chemical Company) (44 mg, 0.287 mmol), tris(dibenzylideneacetone) 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) 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 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(0-50%):hexanes(100-50%) to afford 57 mg (89%) of the title compound as a yellow solid. Mp: 225-227° C. 1H NMR (Acetone-d6, 400 MHz): δ 10.72 (s, 1), 8.14 (d, 2, J=7.0), 8.00 (d, 2, J=8.0), 7.51 (t, 2, J=7.0), 7.44 (t, 1, J=7.0), 7.11 (d, 2, J=8.0), 6.95 (s, 1), 3.91 (s, 3), 2.70 (s, 3). MS m/z: 320 (M+1), 318 (M−1). HRMS (NBA-NaI) m/z Calcd for M++H, C20H17N3O: 316.1450. Found: 316.1450.

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(0-50%)

Sources & evidence

ORD record
ord-67e768febc3f4f85941ea604c4acccac
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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