Sodium Hydroxide → HCID 14075467, compound

HRID 1073771Notes

Reaction equation

HRID 1073771 reaction equation
[CH2:1]([N:3]([CH2:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][N:8]1[CH2:13][C:14]([OH:16])=O)[CH2:4][CH3:5])[CH3:2].[H-].[Na+].[H][H].[Cl:21][C:22]1[CH:37]=[CH:36][C:25]2[C:26](=[O:35])[NH:27][C:28]3[CH:34]=[CH:33][CH:32]=[N:31][C:29]=3[NH:30][C:24]=2[CH:23]=1.[Na].P(Cl)(Cl)(Cl)=O.[OH-].[Na+]>CN(C)C=O>[Cl:21][C:22]1[CH:37]=[CH:36][C:25]2[C:26](=[O:35])[NH:27][C:28]3[CH:34]=[CH:33][CH:32]=[N:31][C:29]=3[N:30]([C:14](=[O:16])[CH2:13][N:8]3[CH2:9][CH2:10][CH2:11][CH2:12][CH:7]3[CH2:6][N:3]([CH2:1][CH3:2])[CH2:4][CH3:5])[C:24]=2[CH:23]=1

Participants

9

Reactant 7

HCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 24813Phosphorus oxychlorideHCID 5360545SodiumHCID 14075456HCID 14075456, compoundHCID 14075465{2-[(Diethylamino)methyl]piperidin-1-yl}acetic acidHCID 178418361HCID 178418361, compound

Product 1

HCID 14075467HCID 14075467, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 14.43 g (0.0632 mole) of 2-[(diethylamino)-methyl]-1-piperidine acetic acid and 2.0 g of a 75% sodium hydride dispersion in liquid paraffin in 160 ml of dimethyl formamide was heated at 50° to 80° C. until evolution of hydrogen had stopped. 15.35 g (0.0625 mole) of 9-chloro-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one were added to the resulting sodium salt of the said acid, and, at -10° C., 9.9 g (0.0646 mole) of phosphorus oxychloride were added dropwise within 10 minutes. The mixture was stirred at -10° C. for 4 hours, at 0° C. for 4 hours and at room temperature for 20 hours. The mixture was stirred into 300 g of ice, the pH was adjusted to 9 with sodium hydroxide solution, and the mixture was exhaustively extracted with dichloromethane. The combined organic phases were washed once with a little ice-water, dried over sodium sulphate and evaporated. The residue was recrystallised from acetonitrile using active charcoal. Colourless crystals of m.p. 167.5-169° C., according to the thin-layer chromatogram, mixed melting point, IR, UV and 1H NMR spectrum completely identical to a sample were obtained as in Example 2. Yield: 5.1 g (18% of theory).

Workup

  1. extractionthe mixture was exhaustively extracted with dichloromethane
  2. washThe combined organic phases were washed once with a little ice-water
  3. dry with materialdried over sodium sulphate
  4. customevaporated
  5. customThe residue was recrystallised from acetonitrile using active charcoal
  6. additionmixed
  7. customwere obtained as in Example 2

Sources & evidence

ORD record
ord-1f3658f088b6413f8c722b7e5cd4db72
Source dataset
uspto-grants-1990_11
Patent number
US04971966

Reaction notes

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