Water → HCID 178506366, compound

HRID 1518139Notes

Reaction equation

HRID 1518139 reaction equation
Cl[C:2](Cl)(Cl)[C:3]1[NH:7][C:6]2[CH:8]=[CH:9][C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[O:18][C:19]([F:22])([F:21])[F:20])=[CH:11][C:5]=2[N:4]=1.[NH2:25][C:26]1([CH2:32][OH:33])[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1.O>O1CCOCC1>[F:20][C:19]([F:22])([F:21])[O:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[C:10]1[CH:9]=[CH:8][C:6]2[NH:7][C:3]([C:2]3[O:33][CH2:32][C:26]4([CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]4)[N:25]=3)=[N:4][C:5]=2[CH:11]=1

Participants

5

Reactant 3

HCID 962WaterHCID 409153(1-Aminocyclohexyl)methanolHCID 178506368HCID 178506368, compound

Product 1

HCID 178506366HCID 178506366, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

2-Trichloromethyl-5-(2-trifluoromethoxy-phenyl)-1H-benzimidazole (241 mg, 0.610 mmol, as prepared in step B of this Example) and (1-amino-cyclohexyl)-methanol (315 mg, 2.44 mmol, as prepared in the previous step) were placed in a 40 mL vial equipped with a magnetic stir bar. Water (8 mL) was added, and the mixture was cooled to 0° C. and stirred at that temperature for 1 h. Complete dissolution of starting materials did not occur, so the mixture was warmed to rt, treated with dioxane (8 mL), and stirred at rt for 14 h. The mixture was extracted three times with EtOAc (20 mL). The combined organic extracts were dried over MgSO4 and concentrated in vacuo. The crude product was purified by column chromatography using a 12-g SiO2 pre-packed column eluting with EtOAc/hexanes, 0:1 to 2:5, v/v over 30 min. The column was repeated under these conditions, yielding 24.6 mg (10%) of the desired compound. 1H-NMR (400 MHz, d6-DMSO) δ: 7.78 (br. s., 1H), 7.46-7.64 (m, 5H), 7.27-7.46 (m, 1H), 4.27 (s, 2H), 1.60-1.82 (m, 6H), 1.47-1.58 (m, 1H), 1.33-1.46 (m, 3H).

Workup

  1. customas prepared in the previous step)
  2. customvial equipped with a magnetic stir bar
  3. dissolutiondissolution of starting materials
  4. temperaturewas warmed to rt
  5. stirringstirred at rt for 14 h
  6. extractionThe mixture was extracted three times with EtOAc (20 mL)
  7. dry with materialThe combined organic extracts were dried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by column chromatography
  10. washeluting with EtOAc/hexanes, 0:1 to 2:5, v/v over 30 min

Sources & evidence

ORD record
ord-7872468e478f4ef1a19a702171065073
Source dataset
uspto-grants-2012_07
Patent number
US08232409B2

Reaction notes

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