Phosgene → HCID 56677933, compound

HRID 1992090Notes

Reaction equation

HRID 1992090 reaction equation
[C:1](Cl)(Cl)=[O:2].[CH3:5][C:6]1[N:10]([CH:11]2[CH2:17][CH:16]3[N:18]([CH2:19][CH2:20][C:21]4([C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=5)[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]4)[CH:13]([CH2:14][CH2:15]3)[CH2:12]2)[C:9]2[CH:33]=[CH:34][CH:35]=[CH:36][C:8]=2[N:7]=1.[CH2:37]([N:39](CC)[CH2:40]C)C>C(Cl)Cl>[CH3:37][N:39]([CH3:40])[C:1]([N:24]1[CH2:23][CH2:22][C:21]([CH2:20][CH2:19][N:18]2[CH:16]3[CH2:15][CH2:14][CH:13]2[CH2:12][CH:11]([N:10]2[C:9]4[CH:33]=[CH:34][CH:35]=[CH:36][C:8]=4[N:7]=[C:6]2[CH3:5])[CH2:17]3)([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:26][CH2:25]1)=[O:2]

Participants

5

Reactant 3

HCID 6371PhosgeneHCID 8471TriethylamineHCID 587278272-Methyl-1-{8-[2-(4-phenyl-4-piperidinyl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-1H-benzimidazole

Product 1

HCID 56677933HCID 56677933, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

At 0° C., to a stirred solution of phosgen (0.25 mL, 2.0 in toluene) was added a solution of 2-methyl-1-{8-[2-(4-phenylpiperidin-4-yl)ethyl]-8-azabicyclo[3.2.1]-oct-3-yl}-1H-benzimidazole (71 mg, 0.17 mmol) in methylene chloride and triethylamine (excess). The mixture was stirred for 30 minutes at 0° C. and further one hour at room temperature. Nitrogene gas was then introduced to remove the excess phosgen. To this mixture was added excess dimethylamine and the resulting mixture was stirred overnight at ambient temperature. After being diluted with methylene chloride, the organic phase was washed with brine, dried over anhydrous sodium sulfate and purified by flash chromatography. N,N-dimethyl-4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidine-1-carboxamid was obtained as foam (52 mg, 63%). 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J=7.3 Hz, 1H), 7.37-7.34 (m, 2H), 7.31-7.29 (m, 3H), 7.23-7.12 (m, 3H), 4.61 (br, 1H), 3.44-3.38 (m, 2H), 3.25 (br, 2H), 3.12-3.06 (m, 2H), 2.80 (s, 6H), 2.58 (s, 3H), 2.38-2.36 (m, 2H), 2.19-2.15 (m, 2H), 1.93-1.81 (m, 10H), 1.61 (d, J=7.3 Hz, 2H). HRMS m/z (M+H)+ calcd: 500.3389, obsd: 500.3386.

Workup

  1. additionNitrogene gas was then introduced
  2. customto remove the excess phosgen
  3. additionTo this mixture was added excess dimethylamine
  4. stirringthe resulting mixture was stirred overnight at ambient temperature
  5. additionAfter being diluted with methylene chloride
  6. washthe organic phase was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. custompurified by flash chromatography

Sources & evidence

ORD record
ord-4f39c035e9d44a8d9f2e10f0fa4ed003
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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