Thiomorpholine → HCID 67543789, compound

HRID 1619828Notes

Reaction equation

HRID 1619828 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.[NH:38]1[CH2:43][CH2:42][S:41][CH2:40][CH2:39]1>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:38]4[CH2:43][CH2:42][S:41][CH2:40][CH2:39]4)(=[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

4

Reactant 2

HCID 67164Thiomorpholine2×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 67543789HCID 67543789, compoundYield 84%

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) (180 mg, 0.335 mmol), thiomorpholine (0.17 mL, 1.68 mmol) in THF (50 mL) was stirred at room temperature for 3 days and then at reflux for 3 hrs. The solvent was removed under vacuum and the residue was dissolved in dioxane (30 mL) and additional thiomorpholine (0.17 mL, 1.68 mmol) was added. The reaction mixture was refluxed for 2 days. The solvent was removed under vacuum and the residue diluted with water. The resulting precipitate was filtered, washed with water and dissolved in CH2Cl2. The solution was dried (Na2SO4) and solvent removed under vacuum. Chromatography on silica, eluting with CH2Cl2/MeOH (98:2), followed by recrystallization from CH2Cl2/hexane gave 180 mg (84% yield) of 2-(difluoromethyl)-4-methoxy-1-[4-(4-morpholinyl)-6-(4-{[2-(4-thiomorpholinyl)ethyl]sulfonyl}-1-piperazinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole: mp (CH2Cl2/hexane) 210-212° C.; 1H NMR (CDCl3) δ 7.86 (dd, J=8.3, 0.5 Hz, 1H), 7.43 (t, JHF=53.5 Hz, 1H), 7.36 (t, J=8.2 Hz, 1H), 6.82 (d, J=7.7 Hz, 1H), 4.05 (s, 3H), 4.00 (br s, 4H), 3.89 (br s, 4H), 3.79 (m, 4H), 3.38 (t, J=5.1 Hz, 4H), 3.11 (dd, J=8.3, 6.1 Hz, 2H), 2.87 (dd, J=8.3, 6.1 Hz, 2H), 2.73 (dd, J=6.1, 3.8 Hz, 4H), 2.63 (m, 4H); Anal. Calcd. for C26H35F2N9O4S2.0.5H2O: C, 48.1; H, 5.6; N, 19.4. Found: C, 48.2; H, 5.4; N, 19.3%.

Workup

  1. temperatureat reflux for 3 hrs
  2. customThe solvent was removed under vacuum
  3. dissolutionthe residue was dissolved in dioxane (30 mL)
  4. temperatureThe reaction mixture was refluxed for 2 days
  5. customThe solvent was removed under vacuum
  6. additionthe residue diluted with water
  7. filtrationThe resulting precipitate was filtered
  8. washwashed with water
  9. dissolutiondissolved in CH2Cl2
  10. dry with materialThe solution was dried (Na2SO4) and solvent
  11. customremoved under vacuum
  12. washChromatography on silica, eluting with CH2Cl2/MeOH (98:2)
  13. customfollowed by recrystallization from CH2Cl2/hexane

Sources & evidence

ORD record
ord-cc0a8e0694b0416999600fd176c6ce54
Source dataset
uspto-grants-2014_07
Patent number
US08772287B2

Reaction notes

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