1,4-Dioxane → HCID 46918341, compound

HRID 516377Notes

Reaction equation

HRID 516377 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.[CH3:38][N:39]1[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1.O1CCOCC1>C1COCC1>[F:37][CH:2]([F:1])[C:3]1[N:7]([C:8]2[N:9]=[C:10]([N:20]3[CH2:21][CH2:22][N:23]([S:26]([CH2:29][CH2:30][N:42]4[CH2:43][CH2:44][N:39]([CH3:38])[CH2:40][CH2:41]4)(=[O:28])=[O:27])[CH2:24][CH2:25]3)[N:11]=[C:12]([N:14]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)[N:13]=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 312751,4-DioxaneHCID 531671-Methylpiperazine2×HCID 469174972-(difluoromethyl)-4-methoxy-1-{4-(4-morpholinyl)-6-[4-(vinylsulfonyl)-1-piperazinyl]-1,3,5-triazin-2-yl}-1H-benzimidazole

Product 1

HCID 46918341HCID 46918341, compoundYield 65.1%

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 1-methylpiperazine (0.16 mL, 1.44 mmol) in THF (20 mL) was refluxed for 5 hrs and then stirred at room temperature for 3 days. Additional 1-methylpiperazine (0.16 mL, 1.44 mmol) and 1,4-dioxane (20 mL) were added and the reaction mixture was refluxed for 20 hrs. The mixture was cooled to room temperature and the solvents were removed under vacuum. The residue was partitioned between CH2Cl2 and H2O. The layers were separated and the aqueous layer was extracted with CH2Cl2 (1×). The combined organic extracts were dried (Na2SO4) and the solvent was removed under vacuum. Chromatography on silica eluting with CH2Cl2/MeOH (100:0 to 95:5) followed by recrystallization from CH2Cl2/hexanes gave 2-(difluoromethyl)-4-methoxy-1-[4-(4-{[2-(4-methyl-1-piperazinyl)ethyl]sulfonyl}-1-piperazinyl)-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (116 mg, 65%).

Workup

  1. temperaturewas refluxed for 5 hrs
  2. temperaturethe reaction mixture was refluxed for 20 hrs
  3. temperatureThe mixture was cooled to room temperature
  4. customthe solvents were removed under vacuum
  5. customThe residue was partitioned between CH2Cl2 and H2O
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with CH2Cl2 (1×)
  8. dry with materialThe combined organic extracts were dried (Na2SO4)
  9. customthe solvent was removed under vacuum
  10. customChromatography on silica eluting with CH2Cl2/MeOH (100:0 to 95:5) followed by recrystallization from CH2Cl2/hexanes

Sources & evidence

ORD record
ord-212d13a41f084f37a387ccd276ae0aaf
Source dataset
uspto-grants-2015_08
Patent number
US09108980B2

Reaction notes

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