Acetonitrile → N-{3-[2-(4-Cyanophenoxy)ethyl]-3-azabicyclo[3.2.1]oct-8-yl}-N'-ethyl-N-methylurea

HRID 411558Notes

Reaction equation

HRID 411558 reaction equation
[CH2:1]([N:3]=[C:4]=[O:5])[CH3:2].[CH3:6][NH:7][CH:8]1[CH:13]2[CH2:14][CH2:15][CH:9]1[CH2:10][N:11]([CH2:16][CH2:17][O:18][C:19]1[CH:26]=[CH:25]C(C#N)=[CH:21][CH:20]=1)[CH2:12]2.[CH3:27][C:28]#[N:29].C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl>[C:28]([C:27]1[CH:21]=[CH:20][C:19]([O:18][CH2:17][CH2:16][N:11]2[CH2:12][CH:13]3[CH:8]([N:7]([CH3:6])[C:4]([NH:3][CH2:1][CH3:2])=[O:5])[CH:9]([CH2:15][CH2:14]3)[CH2:10]2)=[CH:26][CH:25]=1)#[N:29]

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 8022Ethyl isocyanateHCID 11430Potassium CarbonateHCID 185408764-{2-[8-(Methylamino)-3-azabicyclo[3.2.1]oct-3-yl]ethoxy}benzonitrile

Product 1

HCID 18541006N-{3-[2-(4-Cyanophenoxy)ethyl]-3-azabicyclo[3.2.1]oct-8-yl}-N'-ethyl-N-methylurea

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of ethyl isocyanate (0.8 mL, 9.66 mmol) in DCM (3 mL) was added dropwise, at 0° C., to a mixture of 4-{2-[8-(methylamino)-3-azabicyclo[3.2.1]oct-3-yl]ethoxy}benzonitrile (Preparation K; 2.5 g, 8.76 mmol) and MeCN (50 mL). The mixture was stirred at rt for 3 h, K2CO3 (2 g, 14.4 mmol) was added and the mixture was stirred for a further 2 h. Filtration and evaporation gave 2.96 g of crude product. This was purified twice by chromatography on silica gel, the first time eluting with a gradient of EtOAc:MeOH:ammoniacal methanol (10:1:0 to 10:0:1), and the second time eluting with DCM:MeOH:TEA (190:10:1). This gave 2.3 g (71.4%) of the title compound.

Workup

  1. stirringthe mixture was stirred for a further 2 h
  2. filtrationFiltration and evaporation

Sources & evidence

ORD record
ord-9344e7a13e6d44869431287f5e93ee97
Source dataset
uspto-grants-2003_05
Patent number
US06559162B2

Reaction notes

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