Diethylamine → HCID 46918339, compound

HRID 1619846Notes

Reaction equation

HRID 1619846 reaction equation
[F:1][CH:2]([F:37])[C:3]1[N:7]([C:8]2[N:13]=[C:12]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:11]=[C:10]([N:20]3[CH2:25][CH2:24][N:23]([S:26]([CH:29]=[CH2:30])(=[O:28])=[O:27])[CH2:22][CH2:21]3)[N:9]=2)[C:6]2[CH:31]=[CH:32][CH:33]=[C:34]([O:35][CH3:36])[C:5]=2[N:4]=1.[CH2:38]([NH:40][CH2:41][CH3:42])[CH3:39].O1CCOCC1>C1COCC1>[F:37][CH:2]([F:1])[C:3]1[N:7]([C:8]2[N:13]=[C:12]([N:14]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)[N:11]=[C:10]([N:20]3[CH2:21][CH2:22][N:23]([S:26]([CH2:29][CH2:30][N:40]([CH2:41][CH3:42])[CH2:38][CH3:39])(=[O:28])=[O:27])[CH2:24][CH2:25]3)[N:9]=2)[C:6]2[CH:31]=[CH:32][CH:33]=[C:34]([O:35][CH3:36])[C:5]=2[N:4]=1

Participants

5

Reactant 3

HCID 8021Diethylamine2×HCID 312751,4-DioxaneHCID 469174972-(difluoromethyl)-4-methoxy-1-{4-(4-morpholinyl)-6-[4-(vinylsulfonyl)-1-piperazinyl]-1,3,5-triazin-2-yl}-1H-benzimidazole

Product 1

HCID 46918339HCID 46918339, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-(difluoromethyl)-4-methoxy-1-{4-(4-morpholinyl)-6-[4-(vinylsulfonyl)-1-piperazinyl]-1,3,5-triazin-2-yl}-1H-benzimidazole (Example 3) (150 mg, 0.280 mmol) and N,N-diethylamine (0.14 mL, 1.35 mmol) in THF (20 mL) was stirred at room temperature for 17 hrs, refluxed for 1 hr, and then stirred at room temperature for 4 hrs. 1,4-Dioxane (20 mL) was added and the mixture was refluxed for 21 hrs. Additional N,N-diethylamine (0.14 mL, 1.35 mmol) was then added and the mixture was refluxed for another 4.5 hrs. The reaction mixture was cooled to room temperature and the solvents were removed under vacuum. The residue was diluted with water and extracted with CH2Cl2 (2×). The organic layers were combined, dried (Na2SO4), and concentrated under vacuum. Chromatography on silica, eluting with CH2Cl2/MeOH (100:0 to 98:2), gave N-[2-({4-[4-[2-(difluoromethyl)-4-methoxy-1H-benzimidazol-1-yl]-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-1-piperazinyl}sulfonyl)ethyl]-N,N-diethylamine (54 mg, 53%).

Workup

  1. temperaturerefluxed for 1 hr
  2. stirringstirred at room temperature for 4 hrs
  3. temperaturethe mixture was refluxed for 21 hrs
  4. temperaturethe mixture was refluxed for another 4.5 hrs
  5. temperatureThe reaction mixture was cooled to room temperature
  6. customthe solvents were removed under vacuum
  7. additionThe residue was diluted with water
  8. extractionextracted with CH2Cl2 (2×)
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated under vacuum
  11. washChromatography on silica, eluting with CH2Cl2/MeOH (100:0 to 98:2)

Sources & evidence

ORD record
ord-0faa3c123c02484c948136c01e446734
Source dataset
uspto-grants-2014_07
Patent number
US08772287B2

Reaction notes

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