Diisopropylethylamine → N-[(1-(2-Methanesulphonamidoethyl)-4-piperidyl)methyl] 3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carboxamide

HRID 609600

Reaction equation

HRID 609600 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][NH:8][C:9]([C:11]2[C:19]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[N:13]3[CH2:20][CH2:21][CH2:22][O:23][C:12]=23)=[O:10])[CH2:3][CH2:2]1.C(N(C(C)C)CC)(C)C.Br[CH2:34][CH2:35][NH:36][S:37]([CH3:40])(=[O:39])=[O:38]>C(#N)C.C(Cl)(Cl)Cl>[CH3:40][S:37]([NH:36][CH2:35][CH2:34][N:1]1[CH2:6][CH2:5][CH:4]([CH2:7][NH:8][C:9]([C:11]2[C:19]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[N:13]3[CH2:20][CH2:21][CH2:22][O:23][C:12]=23)=[O:10])[CH2:3][CH2:2]1)(=[O:39])=[O:38]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 285330N-(2-bromoethyl)methanesulfonamideHCID 9839803N-(4-Piperidylmethyl) 3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carboxamide

Product 1

HCID 19599423N-[(1-(2-Methanesulphonamidoethyl)-4-piperidyl)methyl] 3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carboxamideYield 11.2%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6342AcetonitrileSolvent

Procedure

A stirred solution of N-(4-piperidylmethyl) 3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carboxarnide (E21, 220 mg, 0.70 mmole) in acetonitrile (8 ml) was treated with diisopropylethylamine (0.24 ml, 1.4 mmole) and N-(2-bromoethyl)methanesulphonamide (D14, 160 mg, 0.77 mmole) and the mixture heated under reflux for 2.5 h. The reaction mixture was concentrated in vacuo and the residue chromatographed on silica gel eluting with dichloromethane/methanol/0.88 ammonia solution (200:10:1). The colourless oil obtained was dissolved in chloroform (30 ml) and washed with water (2×20 ml), then dried (Na2SO4) and concentrated in vacuo. The residue was passed through a short plug of basic alumina eluting with ethyl acetate to afford the title compound as a colourless oil (34 mg, 11%). This was converted to its oxalate salt and crystallised from acetone to give a white solid mp 80-85° C.

Workup

  1. temperaturethe mixture heated
  2. temperatureunder reflux for 2.5 h
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customthe residue chromatographed on silica gel eluting with dichloromethane/methanol/0.88 ammonia solution (200:10:1)
  5. customThe colourless oil obtained
  6. washwashed with water (2×20 ml)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5711a6500e6e49b0bc2937a1673f499b
Source dataset
uspto-grants-1999_12
Patent number
US05998409

Linked notes

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