Hydrochloric Acid → HCID 178468861, compound

HRID 230020

Reaction equation

HRID 230020 reaction equation
[C:1]([C@H:5]1[CH2:10][CH2:9][C@H:8]([NH:11][CH:12]([C:14]2[CH:24]=[CH:23][C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:16][CH:15]=2)[CH3:13])[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[CH3:25]CN(C(C)C)C(C)C.C(Cl)(Cl)=S.[CH3:38][NH:39][C:40]1[C:41]([NH2:46])=[CH:42][CH:43]=[CH:44][CH:45]=1.Cl>ClCCl.FC(F)(F)C([O-])=O.[Hg+2].FC(F)(F)C([O-])=O>[C:1]([C@H:5]1[CH2:10][CH2:9][C@H:8]([N:11]([C:38]2[N:46]([CH3:25])[C:41]3[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=3[N:39]=2)[CH:12]([C:14]2[CH:24]=[CH:23][C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:16][CH:15]=2)[CH3:13])[CH2:7][CH2:6]1)([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 10040ThiophosgeneHCID 78498N-Methyl-o-phenylenediamineHCID 81531Diisopropylethylamine2×HCID 178468863HCID 178468863, compound

Product 1

HCID 178468861HCID 178468861, compound

Reagents, catalysts & solvents 2

HCID 2723924Mercury bis(trifluoroacetate)CatalystHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

To a 0° C. solution of ethyl 4-{1-[(trans-4-tert-butylcyclohexyl)amino]ethyl}benzoate (0.55 g, 1.66 mmol) and DIEA (0.35 mL, 1.99 mmol) in dry dichloromethane (15 mL) was slowly added thiophosgene (0.13 mL, 1.66 mmol). After stirring at 0° C. for 10 min and then at room temperature for 45 min, a solution of N-methylbenzene-1,2-diamine (0.22 g, 1.83 mmol) and DIEA (0.35 mL, 1.99 mmol) in dry dichloromethane (5 mL) was added. The reaction mixture was stirred for 1 h at ambient temperature and then diluted with dichloromethane (20 mL) and poured into aqueous HCl (1N, 20 mL). The organic layer was separated and washed with aqueous HCl (1N, 20 mL), saturated aqueous NaHCO3 (20 mL), brine (20 mL), dried over Na2SO4 and then concentrated to dryness. The residue was dissolved in dichloromethane (20 mL) and mercury (II) trifluoroacetate (0.80 g, 1.86 mmol) was added. The reaction mixture was stirred for 30 min at room temperature and then filtered through Celite. The organic solution was washed with saturated NaHCO3 (20 mL), dried over Na2SO4 and concentrated. Chromatography (15% EtOAc in Hexane) afforded ethyl 4-{1-[(trans-4-tert-butylcyclohexyl)(1-methyl-1H-benzimidazol-2-yl)amino]ethyl}benzoate. HPLC/MS: m/z=462.4 (M+1), Rt=3.46 min. 1H NMR (500 MHz, CDCl3): □ 8.03 (2H, d, J=8.2 Hz), 7.78 (1H, m), 7.52 (2H, d, J=8.2 Hz), 7.28 (3H, m), 4.80 (1H, q, J=6.5 Hz), 4.39 (2H, q, J=7.5 Hz), 3.72 (3H, s), 2.86 (1H, m), 2.14 (1H, m), 1.94 (1H, m), 1.72-1.64 (2H, m), 1.48 (1H, m), 1.41 (3H, t, J=7.5 Hz), 1.17 (3H, d, J=6.5 Hz), 0.95-0.75 (4H, m), 0.73 (9H, s).

Workup

  1. customTo a 0° C.
  2. waitat room temperature for 45 min
  3. stirringThe reaction mixture was stirred for 1 h at ambient temperature
  4. customThe organic layer was separated
  5. washwashed with aqueous HCl (1N, 20 mL), saturated aqueous NaHCO3 (20 mL), brine (20 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness
  8. dissolutionThe residue was dissolved in dichloromethane (20 mL)
  9. stirringThe reaction mixture was stirred for 30 min at room temperature
  10. filtrationfiltered through Celite
  11. washThe organic solution was washed with saturated NaHCO3 (20 mL)
  12. dry with materialdried over Na2SO4
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-2b877f7e8745481cafb2e8ba33458b5f
Source dataset
uspto-grants-2009_07
Patent number
US07563815B2

Linked notes

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