Potassium Carbonate → {5-[3-(2-Aza-bicyclo[3.1.0]hex-2-yl)-propoxy]-1H-indol-2-yl}-morpholin-4-yl-methanone

HRID 132822Notes

Reaction equation

HRID 132822 reaction equation
Cl.[CH:2]12[CH2:7][CH:6]1[CH2:5][CH2:4][NH:3]2.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:15][CH2:16][CH2:17][O:18][C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[NH:24][C:23]([C:28]([N:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1)=[O:29])=[CH:22]2>C(#N)C>[CH:2]12[CH2:7][CH:6]1[CH2:5][CH2:4][N:3]2[CH2:15][CH2:16][CH2:17][O:18][C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[NH:24][C:23]([C:28]([N:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1)=[O:29])=[CH:22]2

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 673581562-Azabicyclo[3.1.0]hexane hydrochlorideHCID 67527317[5-(3-Chloro-propoxy)-1H-indol-2-yl]-morpholin-4-yl-methanone

Product 1

HCID 16754252{5-[3-(2-Aza-bicyclo[3.1.0]hex-2-yl)-propoxy]-1H-indol-2-yl}-morpholin-4-yl-methanoneYield 9.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 2-aza-bicyclo[3.1.0]hexane hydrochloride (example 4 step 7, 49 mg, 1.2 eq.) and potassium carbonate (118 mg, 2.5 eq.) in acetonitrile was stirred 1 h at 60° C. The reaction mixture was cooled to 30° C. and [5-(3-chloro-propoxy)-1H-indol-2-yl]-morpholin-4-yl-methanone (example 4, step 3, 110 mg, 1.0 eq.) was added. The resulting mixture was stirred 24 h at 80° C. The reaction mixture was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with an aqueous solution of sodium hydrogencarbonate and water and dried over sodium sulphate and evaporated in vacuo. The residue was purified on silica, eluting with a 98:2 to 9:1 gradient of dichloromethane/methanol, to yield 12 mg (8%) of the desired product as light yellow solid. MS (m/e): 370.4 (MH+, 100%).

Workup

  1. temperatureThe reaction mixture was cooled to 30° C.
  2. stirringThe resulting mixture was stirred 24 h at 80° C
  3. customThe reaction mixture was partitioned between ethyl acetate and water
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. washthe combined organic layers were washed with an aqueous solution of sodium hydrogencarbonate and water
  6. dry with materialdried over sodium sulphate
  7. customevaporated in vacuo
  8. customThe residue was purified on silica
  9. washeluting with a 98:2 to 9:1 gradient of dichloromethane/methanol

Sources & evidence

ORD record
ord-b63192ca715d46cca4cf20bad06bcf06
Source dataset
uspto-grants-2008_06
Patent number
US07388095B2

Reaction notes

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