Thiophenol → 2-(difluoromethyl)-1-[4-(4-morpholinyl)-6-(phenylsulfanyl)-1,3,5-triazin-2-yl]-1H-benzimidazole

HRID 450148Notes

Reaction equation

HRID 450148 reaction equation
[C:1]1([SH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+].Cl[C:11]1[N:16]=[C:15]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[N:14]=[C:13]([N:23]2[C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=3[N:25]=[C:24]2[CH:32]([F:34])[F:33])[N:12]=1.COCCOCCN(CCOCCOC)CCOCCOC>O.O1CCOCC1>[F:34][CH:32]([F:33])[C:24]1[N:23]([C:13]2[N:14]=[C:15]([N:17]3[CH2:18][CH2:19][O:20][CH2:21][CH2:22]3)[N:16]=[C:11]([S:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[N:12]=2)[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2[N:25]=1

Participants

7

Reactant 4

HCID 7969ThiophenolHCID 14798Sodium HydroxideHCID 112414Ethanamine, 2-(2-methoxyethoxy)-N,N-bis[2-(2-methoxyethoxy)ethyl]-HCID 220368724-(4-chloro-6-(2-(difluoromethyl)-1H-benzo[d]imidazol-1-yl)-1,3,5-triazin-2-yl)morpholine

Product 1

HCID 581028072-(difluoromethyl)-1-[4-(4-morpholinyl)-6-(phenylsulfanyl)-1,3,5-triazin-2-yl]-1H-benzimidazoleYield 76%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

Thiophenol (230 mg, 2.1 mmol) and NaOH (85 mg, 2.1 mmol) were combined in water to give a clear solution, which was then evaporated to dryness. 1-[4-Chloro-6-(4-morpholinyl)-1,3,5-triazin-2-yl]-2-(difluoromethyl)-1H-benzimidazole (184 mg, 0.5 mmol) and tris[2-(2-methoxyethoxy)ethyl]amine (TDA-1; 16 mg, 0.05 mmol) were added and the mixture was heated under reflux in dioxane (10 mL) for 2 hr. After cooling, the mixture was diluted with water to give a solid, which was recrystallised from EtOH to give 167 mg (76% yield) of 2-(difluoromethyl)-1-[4-(4-morpholinyl)-6-(phenylsulfanyl)-1,3,5-triazin-2-yl]-1H-benzimidazole: mp 245-248° C.; 1H NMR (CDCl3) δ 7.83 (t, J=8.6 Hz, 2H), 7.67 (dd, J=8.1, 1.3 Hz, 2H), 7.58 (br t, J=7.4 Hz, 1H), 7.52 (br t, J=7.3 Hz, 2H), 7.34 (dt, J=7.9, 1.2 Hz, 1H), 7.25 (dd, J=7.8, 1.2 Hz, 1H), 6.91 (t, JHF=53.5 Hz, 1H), 3.89 (m, 4H), 3.82-3.77 (m, 4H); Anal. Calc. for C21H18F2N6OS: C, 57.3; H, 4.1; N, 19.1. Found: C, 57.2; H, 4.1; N, 19.2%.

Workup

  1. customto give a clear solution, which
  2. customwas then evaporated to dryness
  3. temperaturethe mixture was heated
  4. temperatureAfter cooling
  5. customto give a solid, which
  6. customwas recrystallised from EtOH

Sources & evidence

ORD record
ord-78925b5dac474be099305e2e41b5c4ad
Source dataset
uspto-grants-2013_07
Patent number
US08486939B2

Reaction notes

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