Diethylamine → 4-acetyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepin-1-ylamine

HRID 1837466Notes

Reaction equation

HRID 1837466 reaction equation
C(C1C=[N:6][NH:7][C:8]2[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=2[CH:10]=1)(=O)C.C1(C)C=C(C)C=C(C)C=1S(ONC(=O)[O:29][CH2:30][CH:31]=C)(=O)=O.[CH2:35]([NH:37]CC)[CH3:36]>C1(C)C=CC=CC=1.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:30]([N:37]1[CH2:10][C:9]2[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=2[N:7]([NH2:6])[CH2:36][CH2:35]1)(=[O:29])[CH3:31]

Participants

7

Reactant 3

HCID 8021DiethylamineHCID 10709271allyl N-[(mesitylsulfonyl)-oxy]carbamateHCID 13809734HCID 13809734, compound

Product 1

HCID 112065194-acetyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepin-1-ylamineYield 44%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

4-Acetylbenzodiazepine (28.5 g, 50.15 m) and allyl N-[(mesitylsulfonyl)-oxy]carbamate (53.8 g, 0.18 m) were combined in toluene (270 mL) and heated under reflux for 2.5 h. The reaction was quenched with 0.5 N NaOH. The precipitate that formed was removed by filtration and the aqueous filtrate was extracted with ethyl acetate (3×). The combined organic layers were washed with saturated sodium chloride solution, dried (MgSO4), and evaporated to give a residue which was dissolved in methylene chloride (490 mL) and treated with diethylamine (51 mL, 5 eq.) and tetrakis triphenylphosphinepalladium (115 mg, 0.001 eq). After stirring for 2 h at room temperature, the volatiles were removed under reduced pressure and the residue was purified by chromatography on silica gel eluting with 10-20% methanol in ethyl acetate to give 4-acetyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepin-1-ylamine (13.5 g, 44%) as a white solid.

Workup

  1. temperatureheated
  2. temperatureunder reflux for 2.5 h
  3. customThe reaction was quenched with 0.5 N NaOH
  4. customThe precipitate that formed
  5. customwas removed by filtration
  6. extractionthe aqueous filtrate was extracted with ethyl acetate (3×)
  7. washThe combined organic layers were washed with saturated sodium chloride solution
  8. dry with materialdried (MgSO4)
  9. customevaporated
  10. customto give a residue which
  11. customthe volatiles were removed under reduced pressure
  12. customthe residue was purified by chromatography on silica gel eluting with 10-20% methanol in ethyl acetate

Sources & evidence

ORD record
ord-dcc180d153994c5b9d4f83e3e0584cdd
Source dataset
uspto-grants-2004_08
Patent number
US06784172B2

Reaction notes

Loading…