Methane → 11-(2-(2-((Diethylamino)methyl)-1-piperidinyl)acetyl)-5,11-dihydro-6H-pyrido(2,3-b)(1,4)benzodiazepin-6-one

HRID 465089Notes

Reaction equation

HRID 465089 reaction equation
Cl[CH2:2][C:3]([N:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[C:9](=[O:16])[NH:8][C:7]2[CH:17]=[CH:18][CH:19]=[N:20][C:6]1=2)=[O:4].Cl.Cl.[CH2:23]([N:25]([CH2:28][CH:29]1[CH2:34][CH2:33][CH2:32][CH2:31][NH:30]1)[CH2:26][CH3:27])[CH3:24].C(=O)([O-])[O-].[Na+].[Na+].C>C(O)CC.Cl.Cl.C(N(CC1CCCCN1)CC)C.C(#N)C>[CH2:23]([N:25]([CH2:28][CH:29]1[CH2:34][CH2:33][CH2:32][CH2:31][N:30]1[CH2:2][C:3]([N:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[C:9](=[O:16])[NH:8][C:7]2[CH:17]=[CH:18][CH:19]=[N:20][C:6]1=2)=[O:4])[CH2:26][CH3:27])[CH3:24]

Participants

8

Reactant 4

HCID 297MethaneHCID 10340Sodium Carbonate2×HCID 12005311-(Chloroacetyl)-5,11-dihydro-6H-pyrido(2,3-b)(1,4)benzodiazepin-6-one2×HCID 20261505Diethyl(piperidin-2-ylmethyl)amine dihydrochloride

Product 1

HCID 10786711-(2-(2-((Diethylamino)methyl)-1-piperidinyl)acetyl)-5,11-dihydro-6H-pyrido(2,3-b)(1,4)benzodiazepin-6-oneYield 65.1%

Reagents, catalysts & solvents 3

HCID 20261505Diethyl(piperidin-2-ylmethyl)amine dihydrochlorideCatalystHCID 10311-PropanolSolventHCID 6342AcetonitrileSolvent

Procedure

A suspension of 11-(chloroacetyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one (276 g, 0.959 mol), and 2-[(diethylamino)methyl]piperidine dihydrochloride (244.95 g, 100.7 mol), of sodium carbonate (223.9 g, 2.112 mol) and acetonitrile (1.92 liters) are stirred for 6 hours at a reaction temperature of 70° C. After this time, the 11-(chloroacetyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one has 95-97% reacted (TLC). The mixture is left to stand overnight at ambient temperature, then suction filtered. The contents of the filter are washed three times, each time with acetonitrile (60 ml). The dark colored filtrates are discarded. The remaining solid is stirred for a further 2 hours with water (1.5 liters), suction filtered again and washed with another water (300 ml) and finally dried at 40° C. in a circulating air drier. The crude product thus obtained (390 g) is transferred into a 10 liter flask, taken up in 1-propanol (5.14 liters) and, after the addition of 2-[(diethylamino)methyl]piperidine dihydrochloride (13.5 g, 0.0555 mol) and anhydrous sodium carbonate (11.8 g, 0.1113 mol), refluxed for 16 hours. After the addition of activated charcoal (39 g) the mixture is heated to boiling for a further 30 minutes and the boiling hot mixture is then forced through a SEITZ filter. Clarification is repeated twice more in the same way using activated charcoal (20 g). The filtrate is left to stand for 12 hours at ambient temperature, the precipitated crystals are suction filtered and washed twice, each time with 1-propanol (50 ml). The product is again stirred with cold 1-propanol (0.5 liters), suction filtered and again washed twice, each time with 1-propanol (50 ml). It is then dried in a circulating air drier at 40° C. and almost colorless crystals (263 g) are obtained, mp. 226°-227° C.

Workup

  1. customreacted (TLC)
  2. waitThe mixture is left
  3. filtrationsuction filtered
  4. washThe contents of the filter are washed three times
  5. filtrationfiltered again
  6. washwashed with another water (300 ml)
  7. customfinally dried at 40° C. in a circulating air drier
  8. customThe crude product thus obtained (390 g)
  9. customis transferred into a 10 liter flask
  10. temperaturerefluxed for 16 hours
  11. temperatureis heated
  12. waitto boiling for a further 30 minutes
  13. filtrationfilter
  14. waitThe filtrate is left
  15. waitto stand for 12 hours at ambient temperature
  16. filtrationfiltered
  17. washwashed twice
  18. stirringThe product is again stirred with cold 1-propanol (0.5 liters), suction
  19. filtrationfiltered
  20. washagain washed twice
  21. customIt is then dried in a circulating air drier at 40° C.

Sources & evidence

ORD record
ord-e83ce60bca7f48ab8a716d358b0b9a27
Source dataset
uspto-grants-1985_10
Patent number
US04550107

Reaction notes

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