Hydrochloric Acid → HCID 21665454, compound

HRID 1110204Notes

Reaction equation

HRID 1110204 reaction equation
[H-].[Na+].[CH2:3]([O:10][C:11]([NH:13][CH:14]1[N:20]=[C:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:18]2[CH:27]=[CH:28][CH:29]=[CH:30][C:17]=2[NH:16][C:15]1=[O:31])=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Cl:32][CH2:33][CH2:34]N(C)C.Cl.[OH-].[Na+]>CN(C=O)C>[Cl:32][CH2:33][CH2:34][N:16]1[C:17]2[CH:30]=[CH:29][CH:28]=[CH:27][C:18]=2[C:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[N:20][CH:14]([NH:13][C:11]([O:10][CH2:3][C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)=[O:12])[C:15]1=[O:31]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 79012-Chloro-N,N-dimethylethylamineHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 2756242Benzyl (2-oxo-5-phenyl-2,3-dihydro-1h-benzo[e][1,4]diazepin-3-yl)carbamate

Product 1

HCID 21665454HCID 21665454, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (26.4 mg of a 50% dispersion in mineral oil; 0.55 mmol) was stirred under nitrogen in dry DMF (5 ml) in an ice bath. (RS)-1,3-Dihydro-3-(benzyloxycarbonyl)amino-5-phenyl-2H-1,4-benzodiazepin-2-one (0.21 g, 0.54 mmol) in DMF (4 ml) was added, and the mixture stirred 1 hr in the cold. (2-Chloroethyl)-dimethylamine (59.2 mg, 0.55 mmol), prepared by distillation of a mixture of the hydrochloride and powdered sodium hydroxide in vacuo, was added and the mixture stirred 1 hr in the cold, and overnight at ambient temperature. The DMF was removed in vacuo and the residue was treated with water and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over sodium sulfate, filtered, and evaporated to dryness in vacuo. The residue was chromatographed on silica gel eluted with 90:10:1:1 of CH2Cl2 :MeOH:H2O:HOAc and the product fractons were evaporated to dryness in vacuo to provide (RS)-1-(2-chloroethyl)-1,3-dihydro-3-(benzyloxycarbonyl) amino-5-phenyl-2H-1,4-benzodiazepin-2-one. This compound (120 mg, 0.268 mmol) was added to a suspension of 10% palladium/Carbon (70 mg) in 4.5% methanolic formic acid (5 ml) stirred at ambient temperature under nitrogen. After 25 min, the mixture was filtered and the filtrate evaporated to dryness in vacuo. The residue was treated with saturated sodium carbonate solution and extracted with ethyl acetate. The combine ethyl acetate layers were washed with water, dried over sodium sulfate, filtered, and evaporated to dryness in vacuo. The residue was dissolved in THF, cooled in an ice bath, and treated with 3-methoxyphenylisocyanate (35.1 μl). The mixture was stirred in the cold for 30 min. warmed to ambient temperature, and filtered. The filtrate was evaporated to dryness in vacuo, and the residue was treated with ether (30 ml) and re-evaporated three times. The residue was triturated with ether and filtered, and the resulting solid dried at 65° C. overnight to provide the title compound: (mp 213°-215° C.). TLC: Silica gel (80:10:1 of CH2Cl2 :CH3OH:NH3) Rf =0.41

Workup

  1. additionwas added
  2. stirringthe mixture stirred 1 hr in the cold, and overnight at ambient temperature
  3. customThe DMF was removed in vacuo
  4. additionthe residue was treated with water
  5. extractionextracted with ethyl acetate
  6. washThe ethyl acetate layer was washed with water
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated to dryness in vacuo
  10. customThe residue was chromatographed on silica gel
  11. washeluted with 90:10:1:1 of CH2Cl2
  12. customMeOH:H2O:HOAc and the product fractons were evaporated to dryness in vacuo

Sources & evidence

ORD record
ord-a20fa48f8db14f609f3906f7cc18d511
Source dataset
uspto-grants-1994_06
Patent number
US05324726

Reaction notes

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