2-Amino-4,6-dichloropyrimidine → HCID 21949205, compound

HRID 2376896Notes

Reaction equation

HRID 2376896 reaction equation
[NH2:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4](Cl)[N:3]=1.[NH2:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][CH:15]=[CH:14]2.C(N(C(C)C)CC)(C)C>CN(C)C=O>[NH2:1][C:2]1[N:7]=[C:6]([NH:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[NH:16][CH:15]=[CH:14]3)[CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 655222-Amino-4,6-dichloropyrimidineHCID 788675-AminoindoleHCID 81531Diisopropylethylamine

Product 1

HCID 21949205HCID 21949205, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 2-amino-4,6-dichloropyrimidine (1.64 g, 10 mmol), 5-aminoindole (1.32 g, 10 mmol), diisopropylethylamine (5.23 ml, 30 mmol) and N,N-dimethylformamide (30 ml) was heated at 60° C. and stirred overnight under nitrogen atmosphere. The reaction mixture was partitioned between ethyl acetate and water after cooled to room temperature; and the organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was distilled off; the obtained residue was dissolved in tetrahydrofuran (100 ml); 10% Palladium on carbon (50% wet, 1.0 g) was added thereto under nitrogen atmosphere; and the reaction mixture was stirred for 4 days under hydrogen atmosphere at atmospheric pressure. The reaction system was purged with nitrogen; the catalyst was filtered off; the filtrate was concentrated under reduced pressure; the residue was purified by NH silica gel column chromatography (eluent; ethyl acetate:methanol=95:5); diethyl ether was added to the residue to crystallize; and the crystals were filtered off, and dried under aeration to yield the title compound (852 mg, 3.8 mmol, 38%) as pale brown crystals.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and water
  2. temperatureafter cooled to room temperature
  3. washand the organic layer was washed with water and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationThe solvent was distilled off
  6. dissolutionthe obtained residue was dissolved in tetrahydrofuran (100 ml)
  7. addition10% Palladium on carbon (50% wet, 1.0 g) was added
  8. stirringand the reaction mixture was stirred for 4 days under hydrogen atmosphere at atmospheric pressure
  9. customThe reaction system was purged with nitrogen
  10. filtrationthe catalyst was filtered off
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customthe residue was purified by NH silica gel column chromatography (eluent; ethyl acetate:methanol=95:5)
  13. additiondiethyl ether was added to the residue
  14. customto crystallize
  15. filtrationand the crystals were filtered off
  16. customdried under aeration

Sources & evidence

ORD record
ord-ffa864e575f24355b2eba0650cca561c
Source dataset
uspto-grants-2008_12
Patent number
US07468380B2

Reaction notes

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