N-Methylcyclohexylamine → HCID 19961906, compound

HRID 1755642Notes

Reaction equation

HRID 1755642 reaction equation
[O:1]=[C:2]1[CH:8]=[N:7][C:6](=O)[C:5]2[CH:10]=[CH:11][CH:12]=[CH:13][C:4]=2[N:3]1[CH2:14][CH2:15][CH3:16].P(Cl)(Cl)(Cl)(Cl)Cl.[CH3:23][NH:24][CH:25]1[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1>ClCCl>[CH:25]1([N:24]([C:6]2[C:5]3[CH:10]=[CH:11][CH:12]=[CH:13][C:4]=3[N:3]([CH2:14][CH2:15][CH3:16])[C:2](=[O:1])[CH2:8][N:7]=2)[CH3:23])[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1

Participants

5

Reactant 3

HCID 7514N-MethylcyclohexylamineHCID 24819Phosphorus pentachlorideHCID 23353154HCID 23353154, compound

Product 1

HCID 19961906HCID 19961906, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of 2,5-dioxo-1-propyl-1,4-benzodiazepine (see Example 8) (10.0 g, 0.046 mol) in dichloromethane (200 ml) was added phosphorus pentachloride (11.5 g, 0.055 mol) in dichloromethane (400 ml) over 30 minutes. The reaction mixture was stirred at room temperature for 2 h then the solvent was removed under vacuum and the resulting oil was dried under high vacuum. The oil was redissolved in dichloromethane (200 ml) and a solution of N-methylcyclohexylamine (15.6 g, 0.138 mol) in dichloromethane (125 ml) was added dropwise. When the addition was complete, the reaction mixture was allowed to stir for 18 hours. The solution was washed with saturated sodium hydrogen carbonate solution (100 ml), and the aqueous layer was reextracted with dichloromethane (2×100 ml). The combined organic layers were washed with brine (100 ml), dried (sodium sulphate), filtered and concentrated in vacuo. The residue was dissolved in a small amount of dichloromethane and purified by flash column chromatography, eluted with 2% methanol/0.5% 0.88 ammonia solution/dichloromethane (3 litres) then 5% methanol/0.5% 0.88 ammonia solution/dichloromethane. Yield=15.8 g (quantitative), as a brown oil. 1H NMR (DMSO)δ0.68 (3H, t, J=7.3 Hz), 1.84-2.04 (3H, m), 2.72 (3H, s), 3.40 (1H, d, J=12.2 Hz), 3.54 (1H, m), 3.88 (1H, d, J= 12.2 Hz), 4.22 (1H, m), 7.34 (1H, m), 7.50 (1H, d, J=7.43 Hz), 7.60 (2H, m).

Workup

  1. customthe solvent was removed under vacuum
  2. customthe resulting oil was dried under high vacuum
  3. dissolutionThe oil was redissolved in dichloromethane (200 ml)
  4. additionWhen the addition
  5. stirringto stir for 18 hours
  6. washThe solution was washed with saturated sodium hydrogen carbonate solution (100 ml)
  7. washThe combined organic layers were washed with brine (100 ml)
  8. dry with materialdried (sodium sulphate)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. dissolutionThe residue was dissolved in a small amount of dichloromethane
  12. custompurified by flash column chromatography
  13. washeluted with 2% methanol/0.5% 0.88 ammonia solution/dichloromethane (3 litres)

Sources & evidence

ORD record
ord-6e0e2917cfaa454f8d69adad71935040
Source dataset
uspto-grants-1995_08
Patent number
US05438055

Reaction notes

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