Acetic Acid → 4-(4-Chlorobenzoyl)-1-[4-(2,5-dihydro-1h-pyrrol-1-ylcarbonyl)benzyl]-6-methoxy-1,3,4,5-tetrahydrobenzo[e][1,4]diazepin-2-on

HRID 2417514Notes

Reaction equation

HRID 2417514 reaction equation
CO[C:3]1[CH:16]=[CH:15][C:6]([CH2:7][NH:8][CH2:9][C:10]([O:12]CC)=O)=[C:5]([N+:17]([O-])=O)[CH:4]=1.[Cl:20][C:21]1[CH:29]=[CH:28][C:24]([C:25](Cl)=[O:26])=[CH:23][CH:22]=1.C(N(CC)CC)C.[H][H].[N:39]1([C:44]([C:46]2[CH:53]=[CH:52][C:49]([CH:50]=O)=[CH:48][CH:47]=2)=[O:45])[CH2:43][CH:42]=[CH:41][CH2:40]1.[C:54](O)(=[O:56])C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.C(OCC)(=O)C.[OH-].[Na+].C(O)C.[Pd]>[Cl:20][C:21]1[CH:29]=[CH:28][C:24]([C:25]([N:8]2[CH2:7][C:6]3[C:15]([O:56][CH3:54])=[CH:16][CH:3]=[CH:4][C:5]=3[N:17]([CH2:50][C:49]3[CH:52]=[CH:53][C:46]([C:44]([N:39]4[CH2:43][CH:42]=[CH:41][CH2:40]4)=[O:45])=[CH:47][CH:48]=3)[C:10](=[O:12])[CH2:9]2)=[O:26])=[CH:23][CH:22]=1

Participants

13

Reactant 7

HCID 176Acetic AcidHCID 8471Triethylamine2×HCID 85014-Chlorobenzoyl chlorideHCID 5049666Sodium triacetoxyborohydrideHCID 226325974-(2,5-dihydro-1H-pyrrol-1-ylcarbonyl)benz-aldehydeHCID 86589883Ethyl (4-methoxy-2-nitrobenzyl)aminoacetateHCID 178418361HCID 178418361, compound

Product 1

HCID 226324534-(4-Chlorobenzoyl)-1-[4-(2,5-dihydro-1h-pyrrol-1-ylcarbonyl)benzyl]-6-methoxy-1,3,4,5-tetrahydrobenzo[e][1,4]diazepin-2-on

Reagents, catalysts & solvents 5

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolvent5×HCID 8857Ethyl AcetateSolvent2×HCID 14798Sodium HydroxideSolvent

Procedure

3.6 g (13.7 mmol) of ethyl (4-methoxy-2-nitrobenzyl)aminoacetate was dissolved in 50 ml of dichloromethane. 2.1 ml (16.4 mmol) of 4-chlorobenzoyl chloride and 2.9 ml (20.6 mmol) of triethylamine were added to the obtained solution under cooling with ice, and they were stirred under cooling with ice for 2 hours. After the treatment with dichloromethane as the extracting solvent by an ordinary method, the crude product was obtained. The crude product was dissolved in 50 ml of ethyl acetate. 360 mg of 10% palladium/carbon was added to the obtained solution and they were stirred in the presence of hydrogen at room temperature for 4 hours. The reaction solution was filtered through Celite. The solvent was evaporated to obtain the crude product. 243 mg (0.65 mmol) of the crude product was dissolved in 5 ml of dichloromethane. 156 mg (0.78 mmol) of 4-(2,5-dihydro-1H-pyrrol-1-ylcarbonyl)benzaldehyde and 0.074 ml (1.3 mmol) of acetic acid were added to the obtained solution, and they were stirred at room temperature for 30 minutes. 340 mg (1.6 mmol) of sodium triacetoxyborohydride was added to the reaction mixture, and they were stirred at room temperature overnight. After the treatment with dichloromethane as the extracting solvent by an ordinary method, the obtained crude product was dissolved in a mixture of 2 ml of 1 N sodium hydroxide and 10 ml of ethanol, and the obtained solution was stirred at room temperature for 5 hours. After the treatment with ethyl acetate as the extracting solvent by an ordinary method, the obtained crude product was dissolved in 5 ml of dichloromethane. 131 mg (0.78 mmol) of 2-chloro-1,3-dimethylimidazonium chloride and 0.19 ml (1.3 mmol) of triethylamine were added to the obtained solution, and they were stirred overnight. The solvent was evaporated, and the obtained crude product was treated in the same manner as in step 3 in Example 1 to obtain the title compound.

Workup

  1. temperatureunder cooling with ice, and they
  2. temperatureunder cooling with ice for 2 hours
  3. filtrationThe reaction solution was filtered through Celite
  4. customThe solvent was evaporated
  5. customto obtain the crude product
  6. stirringwere stirred at room temperature for 30 minutes
  7. stirringwere stirred at room temperature overnight
  8. stirringthe obtained solution was stirred at room temperature for 5 hours
  9. stirringwere stirred overnight
  10. customThe solvent was evaporated
  11. customthe obtained crude product
  12. additionwas treated in the same manner as in step 3 in Example 1

Sources & evidence

ORD record
ord-842ebded47f04d10899cde8a5c561c57
Source dataset
uspto-grants-2004_11
Patent number
US06825191B2

Reaction notes

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