Hydrogen Bromide → HCID 19070843, compound

HRID 1489520Notes

Reaction equation

HRID 1489520 reaction equation
Br.[C:2]1([C:8]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[NH:12][C:11](=[S:19])[C@H:10]([NH:20][C:21](=O)[O:22]CC3C=CC=CC=3)[N:9]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.C(Cl)(=O)C(Cl)=O.[CH:44]1([CH2:50][CH2:51]C(O)=O)[CH2:49][CH2:48][CH2:47][CH2:46][CH2:45]1>CN(C=O)C.C1COCC1.ClCCl.C(O)(=O)C>[CH:44]1([CH2:50][CH2:51][C:21]([NH:20][CH:10]2[N:9]=[C:8]([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[NH:12][C:11]2=[S:19])=[O:22])[CH2:49][CH2:48][CH2:47][CH2:46][CH2:45]1

Participants

10

Reactant 5

HCID 260Hydrogen BromideHCID 8471Triethylamine2×HCID 65578Oxalyl chlorideHCID 69702Cyclohexanepropanoic acidHCID 22855234HCID 22855234, compound

Product 1

HCID 19070843HCID 19070843, compound

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 176Acetic AcidSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Hydrogen bromide was bubbled at room temperature through a solution of (+)-phenylmethyl N-[(3R)-2,3-dihydro-5-phenyl-2-thioxo-1H-1,4-benzodiazepin-3-yl]carbamate (0.9 g, 2.1 mmol), acetic acid (5 mL) and dichloromethane (5 mL). After 2 h., the solvent was evaporated under reduced pressure, ether was added and the solid was collected and dried in vacuo. A sample (0.58 g, 1.8 mmol) was suspended in THF (10 mL), triethylamine (0.24 mL, 0.18 g, 1.8 mmol) was added and the mixture was stirred at room temperature for 3 h. In a separate flask, oxalyl chloride (0.20 mL, 0.29 g, 2.3 mmol) was added to a solution of cyclohexanepropionic acid (0.33 mL, 0.30 g, 1.9 mmol) and DMF (1 drop) in THF (10 mL) and the mixture was stirred at room temperature for 3 h. The two mixtures were combined, triethylamine (0.32 mL, 0.23 g, 2.3 mmol) was added and the mixture was stirred at room temperature for 2.5 h. The solvent was evaporated under reduced pressure, water was added and the mixture was extracted with ethyl acetate. The combined organic fractions were washed with water, saturated aqueous sodium hydrogen carbonate, water (2×) and brine, dried (Na2SO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with CH2Cl2 /MeOH (99.5:0.5) and the residue was recrystallized from EtOAc/Hexane to give 3-cyclohexyl-N-(2,3-dihydro-5-phenyl-2-thioxo-1H-1,4-benzodiazepin-3-yl)propanamide as a solid. m.p. 113°-119° C.

Workup

  1. customthe solvent was evaporated under reduced pressure, ether
  2. additionwas added
  3. customthe solid was collected
  4. customdried in vacuo
  5. stirringthe mixture was stirred at room temperature for 3 h
  6. stirringthe mixture was stirred at room temperature for 2.5 h
  7. customThe solvent was evaporated under reduced pressure, water
  8. additionwas added
  9. extractionthe mixture was extracted with ethyl acetate
  10. washThe combined organic fractions were washed with water, saturated aqueous sodium hydrogen carbonate, water (2×) and brine
  11. dry with materialdried (Na2SO4)
  12. customthe solvent was evaporated under reduced pressure
  13. customThe residue was purified by flash column chromatography on silica gel
  14. washeluting with CH2Cl2 /MeOH (99.5:0.5)
  15. customthe residue was recrystallized from EtOAc/Hexane

Sources & evidence

ORD record
ord-f9a20c06a04b4945bd2e1674696a6725
Source dataset
uspto-grants-1997_10
Patent number
US05679672

Reaction notes

Loading…