3,4-Dichlorophenyl isocyanate → N-(3,4-dichlorophenyl)-4-[(1-ethylpiperidin-3-yl)methyl]-1,4-diazepane-1-carboxamide

HRID 603186Notes

Reaction equation

HRID 603186 reaction equation
[N:1]1([C:8]([O:10]C(C)(C)C)=O)[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.CC1C=CC(S(O[CH2:26][CH:27]2[CH2:32][CH2:31][CH2:30][N:29]([CH2:33][CH3:34])[CH2:28]2)(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+].C(N(C(C)C)CC)(C)C.[Cl:50][C:51]1[CH:52]=[C:53]([N:58]=C=O)[CH:54]=[CH:55][C:56]=1[Cl:57]>C(#N)C.ClCCl.CN(C)C=O>[Cl:50][C:51]1[CH:52]=[C:53]([NH:58][C:8]([N:1]2[CH2:7][CH2:6][CH2:5][N:4]([CH2:26][CH:27]3[CH2:32][CH2:31][CH2:30][N:29]([CH2:33][CH3:34])[CH2:28]3)[CH2:3][CH2:2]2)=[O:10])[CH:54]=[CH:55][C:56]=1[Cl:57]

Participants

9

Reactant 5

HCID 76073,4-Dichlorophenyl isocyanateHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 2756058Tert-butyl 1,4-diazepane-1-carboxylateHCID 57656762(1-Ethylpiperidin-3-yl)methyl 4-methylbenzenesulfonate

Product 1

HCID 11524440N-(3,4-dichlorophenyl)-4-[(1-ethylpiperidin-3-yl)methyl]-1,4-diazepane-1-carboxamideYield 56.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of tert-butyl 1,4-diazepane-1-carboxylate (81 mg), (1-ethylpiperidin-3-yl)methyl 4-methylbenzenesulfonate (100 mg) and potassium carbonate (186 mg) in acetonitrile (3 mL) was heated to 100° C. in the microwave for 1 hour 15 minutes. The mixture was filtered and evaporated. The residue was purified by silica column chromatography, eluting with a gradient of 0 to 5% 7M NH3/MeOH in dichloromethane. To a solution of the isolated material (100 mg) in methanol (5 mL) was added 4M hydrochloric acid in dioxane (2 mL). The mixture was stirred for 6 hours at room temperature and then evaporated to give a colourless oil. To a mixture of this oil (150 mg) in dichloromethane (10 mL) and dimethylformamide (1 mL) was added di-iso-propylethylamine (0.31 mL) and 3,4-dichlorophenylisocyanate (100 mg). The mixture was stirred for 15 minutes and then evaporated. The residue was purified using reverse phase HPLC eluting with a mixture of 5-95% acetonitrile in water to give the title compound as a white solid (78 mg, 56%).

Workup

  1. filtrationThe mixture was filtered
  2. customevaporated
  3. customThe residue was purified by silica column chromatography
  4. washeluting with a gradient of 0 to 5% 7M NH3/MeOH in dichloromethane
  5. additionTo a solution of the isolated material (100 mg) in methanol (5 mL) was added 4M hydrochloric acid in dioxane (2 mL)
  6. customevaporated
  7. customto give a colourless oil
  8. stirringThe mixture was stirred for 15 minutes
  9. customevaporated
  10. customThe residue was purified
  11. washeluting with a mixture of 5-95% acetonitrile in water

Sources & evidence

ORD record
ord-b3db6ef9f0684dcab7554c4e237e372d
Source dataset
uspto-grants-2011_03
Patent number
US07906645B2

Reaction notes

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