Diisopropylethylamine → HCID 178423986, compound

HRID 1912652Notes

Reaction equation

HRID 1912652 reaction equation
C([O:8][C:9]1[C:10]([C:22](O)=O)=[N:11][CH:12]=[N:13][C:14]=1[C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=1)C1C=CC=CC=1.[NH2:25][C:26]1[CH:27]=[C:28]([CH:31]=[CH:32][C:33]=1[NH2:34])[C:29]#[N:30].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C>[OH:8][C:9]1[C:10]([C:22]2[NH:34][C:33]3[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][C:26]=3[N:25]=2)=[N:11][CH:12]=[N:13][C:14]=1[C:15]1[CH:16]=[CH:17][C:18]([CH3:21])=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 7372853,4-DiaminobenzonitrileHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66958350HCID 66958350, compound

Product 1

HCID 178423986HCID 178423986, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-(benzyloxy)-6-p-tolylpyrimidine-4-carboxylic acid P72 (80 mg, 0.25 mmol) in DMF (3 mL) was added 3,4-diaminobenzonitrile (40 mg, 0.30 mmol), HATU (124 mg, 0.33 mmol) and diisopropylethylamine (48 mg, 0.37 mmol). The reaction mixture was stirred at room temperature for 18 hours. The organic solvent was evaporated under reduced pressure. Ethyl acetate and 1 N hydrochloric acid were added. The organic layer was washed with water and saturated brine. The organic layer was dried over anhydrous sodium sulfate. The organic solvent was evaporated under reduced pressure. The intermediate was purified by flash column chromatography. The intermediate was dissolved in acetic acid (5 mL) and heated in a microwave reactor at 160° C. for 1 hour. The organic solvent was evaporated under reduced pressure. Trifluoroacetic acid (5 mL) was added and the solution was heated in a microwave reactor at 120° C. for 30 minutes. The organic solvent was evaporated under reduced pressure. The crude product was purified by RP-HPLC to afford the desired 2-(5-hydroxy-6-p-tolylpyrimidin-4-yl)-1H-benzo[d]imidazole-5-carbonitrile P73 (16 mg, 0.049 mmol).

Workup

  1. customThe organic solvent was evaporated under reduced pressure
  2. additionEthyl acetate and 1 N hydrochloric acid were added
  3. washThe organic layer was washed with water and saturated brine
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. customThe organic solvent was evaporated under reduced pressure
  6. customThe intermediate was purified by flash column chromatography
  7. dissolutionThe intermediate was dissolved in acetic acid (5 mL)
  8. temperatureheated in a microwave reactor at 160° C. for 1 hour
  9. customThe organic solvent was evaporated under reduced pressure
  10. additionTrifluoroacetic acid (5 mL) was added
  11. temperaturethe solution was heated in a microwave reactor at 120° C. for 30 minutes
  12. customThe organic solvent was evaporated under reduced pressure
  13. customThe crude product was purified by RP-HPLC

Sources & evidence

ORD record
ord-c060387717e54eb19f13e8213b1648fc
Source dataset
uspto-grants-2013_12
Patent number
US08609676B2

Reaction notes

Loading…