Lawesson's reagent → 1,3-Dihydro-5-cyclohexyl-3(R,S)-[(benzyloxycarbonyl)-amino]-2H-1,4-benzodiazepin-2-thione

HRID 355681Notes

Reaction equation

HRID 355681 reaction equation
[CH:1]1([C:7]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[NH:11][C:10](=O)[CH:9]([NH:19][C:20]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[O:21])[N:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.COC1C=CC(P2(=S)SP(=S)(C3C=CC(OC)=CC=3)[S:39]2)=CC=1>C1(C)C=CC=CC=1>[CH:1]1([C:7]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[NH:11][C:10](=[S:39])[CH:9]([NH:19][C:20]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[O:21])[N:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 87949Lawesson's reagentHCID 135413400Z-(R,S)-3-amino-5-cyclohexyl-2-oxo-1,4-benzodiazepine

Product 1

HCID 1357532921,3-Dihydro-5-cyclohexyl-3(R,S)-[(benzyloxycarbonyl)-amino]-2H-1,4-benzodiazepin-2-thione

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

1,3-Dihydro-5-cyclohexyl-3(R,S)-[(benzyloxycarbonyl)-amino]-2H-1,4-benzodiazepin-2-one (M. Chambers, et. al. Biomed. Chem. Lett. 1993, in press) (1.09 g, 2.79 mmole) was mixed with 1.13 g (2.79 mmole) of 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide in 26 ml of toluene. The resulting suspension was heated to reflux for 1 hour. The reaction mixture was cooled, filtered, and concentrated in vacuo. The residue was flash chromatographed on silica gel (ethyl acetate-hexane, 1:3) and the product containing fractions were pooled and concentrated to give the title compound in approximately 85% purity. This material was recrystallized from hexane-ethyl acetate (1:1) to give 850 mg (75%) of the title compound in analytical form: m.p. 164°-165° C.

Workup

  1. temperatureThe resulting suspension was heated
  2. temperatureto reflux for 1 hour
  3. temperatureThe reaction mixture was cooled
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customchromatographed on silica gel (ethyl acetate-hexane, 1:3)
  7. additionthe product containing fractions
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-b3b579e32430491d96e998cacb2eeb63
Source dataset
uspto-grants-1998_11
Patent number
US05834464

Reaction notes

Loading…