Acetic Acid → 6-chloro-4-(4-chlorobenzoyl)-1-[4-(2,5-dihydro-1H-pyrrol-1-ylcarbonyl)benzyl]-7-methyl-1,3,4,5-tetrahydro-benzo[e][1,4]-diazepin-2-on

HRID 2417502Notes

Reaction equation

HRID 2417502 reaction equation
[NH2:1][C:2]1[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[C:3]=1[CH2:4][N:5]([CH2:15][C:16](OCC)=[O:17])[C:6](=[O:14])[C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][CH:8]=1.[N:26]1([C:31]([C:33]2[CH:40]=[CH:39][C:36]([CH:37]=O)=[CH:35][CH:34]=2)=[O:32])[CH2:30][CH:29]=[CH:28][CH2:27]1.[C:41](O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(N(CC)CC)C>ClCCl.[OH-].[Na+].C(O)C.Cl.O1CCOCC1.C(OCC)(=O)C>[Cl:25][C:21]1[C:3]2[CH2:4][N:5]([C:6](=[O:14])[C:7]3[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][CH:8]=3)[CH2:15][C:16](=[O:17])[N:1]([CH2:37][C:36]3[CH:39]=[CH:40][C:33]([C:31]([N:26]4[CH2:30][CH:29]=[CH:28][CH2:27]4)=[O:32])=[CH:34][CH:35]=3)[C:2]=2[CH:24]=[CH:23][C:22]=1[CH3:41]

Participants

12

Reactant 5

HCID 176Acetic AcidHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 226325974-(2,5-dihydro-1H-pyrrol-1-ylcarbonyl)benz-aldehydeHCID 86589878Ethyl [(2-amino-6-chlorobenzyl)-(4-chlorobenzoyl)amino]acetate

Product 1

HCID 226324016-chloro-4-(4-chlorobenzoyl)-1-[4-(2,5-dihydro-1H-pyrrol-1-ylcarbonyl)benzyl]-7-methyl-1,3,4,5-tetrahydro-benzo[e][1,4]-diazepin-2-on

Reagents, catalysts & solvents 6

HCID 313Hydrochloric AcidSolventHCID 702EthanolSolventHCID 6344DichloromethaneSolvent3×HCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolventHCID 312751,4-DioxaneSolvent

Procedure

140 mg (0.37 mmol) of ethyl [(2-amino-6-chlorobenzyl)-(4-chlorobenzoyl)amino]acetate and 89 mg (0.44 mmol) of 4-(2,5-dihydro-1H-pyrrol-1-ylcarbonyl)benzaldehyde were dissolved in 5 ml of dichloromethane. 0.042 ml (0.74 mmol) of acetic acid was added to the obtained solution, and they were stirred at room temperature for 30 minutes. 195 mg (0.93 mmol) of sodium triacetoxyborohydride was added to the obtained solution, 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 5 ml of 1 N sodium hydroxide and 5 ml of ethanol, and they were stirred at room temperature for 4 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. 74 mg (0.44 mmol) of 2-chloro-1,3-dimethylimidazonium chloride and 0.1 ml (0.74 mmol) of triethylamine were added to the obtained solution, and they were stirred overnight. The solvent was evaporated and the obtained crude product was dissolved in 5 ml of 4N solution of hydrogen chloride in dioxane. The obtained solution was stirred at room temperature for 3 hours. 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. stirringwere stirred at room temperature overnight
  2. stirringwere stirred at room temperature for 4 hours
  3. stirringwere stirred overnight
  4. customThe solvent was evaporated
  5. customthe obtained crude product
  6. stirringThe obtained solution was stirred at room temperature for 3 hours
  7. customThe solvent was evaporated
  8. customthe obtained crude product
  9. additionwas treated in the same manner as in Step 3 in Example 1

Sources & evidence

ORD record
ord-f9d3cb2c9d2b44eeafc106ba885d5aed
Source dataset
uspto-grants-2004_11
Patent number
US06825191B2

Reaction notes

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