Sodium Hydroxide → HCID 14374295, compound

HRID 1681816Notes

Reaction equation

HRID 1681816 reaction equation
[N:1]1([CH2:7][CH2:8][CH2:9][CH:10]2[CH2:15][CH2:14][N:13]([CH2:16][C:17]([OH:19])=O)[CH2:12][CH2:11]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[H][H].[Na].[N:25]1[C:30]2[NH:31][C:32]3[CH:40]=[CH:39][CH:38]=[CH:37][C:33]=3[C:34](=[O:36])[NH:35][C:29]=2[CH:28]=[CH:27][CH:26]=1.P(Cl)(Cl)(Cl)=O.[OH-].[Na+]>CN(C)C=O>[N:1]1([CH2:7][CH2:8][CH2:9][CH:10]2[CH2:11][CH2:12][N:13]([CH2:16][C:17]([N:31]3[C:32]4[CH:40]=[CH:39][CH:38]=[CH:37][C:33]=4[C:34](=[O:36])[NH:35][C:29]4[CH:28]=[CH:27][CH:26]=[N:25][C:30]3=4)=[O:19])[CH2:14][CH2:15]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

9

Reactant 7

HCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 24813Phosphorus oxychlorideHCID 701695,11-Dihydro-6H-pyrido(2,3-b)(1,4)benzodiazepin-6-oneHCID 5360545SodiumHCID 19804231HCID 19804231, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 14374295HCID 14374295, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 16.90 g (0.063 mol) of 4-[3-(1-piperidinyl)-propyl]piperidinoacetic acid and 2.0 g of a 75% sodium hydride dispersion in paraffin oil is heated in 160 ml of dimethylformamide at 50°-80° C. until the development of hydrogen has ended. To the resulting sodium salt of the above-mentioned acid are added 13.0 g (0.062 mol) of 5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin- 6-one and at -10° C. 9.8 g (0.064 mol) of phosphorus oxychloride are added dropwise within 10 minutes. The resulting mixture is stirred for 4 hours at -10° C., for 4 hours at 0° C. and for 20 hours at ambient temperature. Then the mixture is stirred into 300 g of ice, adjusted to pH 9 with sodium hydroxide solution and extracted exhaustively with dichloromethane. The combined organic phases are washed once with a little ice water, dried over sodium sulphate and concentrated by evaporation. The residue is recrystallised from ethyl acetate using activated charcoal. Colourless crystals, m.p. 202°-203° C., totally identical to a sample obtained in Example 3 according to thin layer chromatography, mixed melting point, IR, UV and 1H-NMR spectra. Yield: 4.57 g (16% of theory).

Workup

  1. customat -10° C
  2. extractionextracted exhaustively with dichloromethane
  3. washThe combined organic phases are washed once with a little ice water
  4. dry with materialdried over sodium sulphate
  5. concentrationconcentrated by evaporation
  6. customThe residue is recrystallised from ethyl acetate using activated charcoal
  7. customColourless crystals, m.p. 202°-203° C., totally identical to a sample obtained in Example 3 according to thin layer chromatography
  8. additionmixed

Sources & evidence

ORD record
ord-714a66e4617242a2aca00e839796ebb8
Source dataset
uspto-grants-1992_12
Patent number
US05175158

Reaction notes

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