Acetic Acid → Diethyl [2-(4-(4-chlorobenzoyl)-2-oxo-1-(4-(1-pyrrolidinecarbonyl)benzyl)-2,3,4,5-tetrahydro-1H-benzo[e][1,4]-diazepin-8-yl)ethyl]phosphonate

HRID 2417489Notes

Reaction equation

HRID 2417489 reaction equation
[Cl:1][C:2]1[CH:34]=[CH:33][C:5]([C:6]([N:8]([CH2:27][C:28](OCC)=[O:29])[CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:16][CH2:17][P:18]([O:23][CH2:24][CH3:25])([O:20][CH2:21][CH3:22])=[O:19])=[CH:12][C:11]=2[NH2:26])=[O:7])=[CH:4][CH:3]=1.[N:35]1([C:40]([C:42]2[CH:49]=[CH:48][C:45]([CH:46]=O)=[CH:44][CH:43]=2)=[O:41])[CH2:39][CH2:38][CH2:37][CH2:36]1.C(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.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:9][C:10]3[CH:15]=[CH:14][C:13]([CH2:16][CH2:17][P:18](=[O:19])([O:23][CH2:24][CH3:25])[O:20][CH2:21][CH3:22])=[CH:12][C:11]=3[N:26]([CH2:46][C:45]3[CH:44]=[CH:43][C:42]([C:40]([N:35]4[CH2:39][CH2:38][CH2:37][CH2:36]4)=[O:41])=[CH:49][CH:48]=3)[C:28](=[O:29])[CH2:27]2)=[O:7])=[CH:33][CH:34]=1

Participants

10

Reactant 5

HCID 176Acetic AcidHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 127880444-(Pyrrolidine-1-carbonyl)benzaldehydeHCID 86589876HCID 86589876, compound

Product 1

HCID 60123509Diethyl [2-(4-(4-chlorobenzoyl)-2-oxo-1-(4-(1-pyrrolidinecarbonyl)benzyl)-2,3,4,5-tetrahydro-1H-benzo[e][1,4]-diazepin-8-yl)ethyl]phosphonate

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent3×HCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Procedure

240 mg (0.47 mmol) of ethyl ((4-chlorobenzoyl)-(4-(2-(diethoxyphosphoryl)ethyl)-2-aminobenzyl)amino)acetate and 105 mg (0.52 mmol) of 4-(1-pyrrolidinecarbonyl)benzaldehyde were dissolved in 10 ml of dichloromethane. 0.054 ml (0.94 mmol) of acetic acid was added to the obtained solution. They were stirred at room temperature for 30 minutes. 248 mg (1.18 mmol) of sodium triacetoxyborohydride was added to the obtained 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 4 ml of 1 N sodium hydroxide and 2 ml of ethanol, and the solution was stirred at room temperature for 5 hours. After the treatment with ethyl acetate by an ordinary method, the obtained crude product was dissolved in 10 ml of dichloromethane. 95 mg (0.56 mmol) of 2-chloro-1,3-dimethylimidazonium chloride and 0.14 ml (0.94 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. stirringwere stirred at room temperature overnight
  2. stirringthe solution was stirred at room temperature for 5 hours
  3. stirringwere stirred overnight
  4. customThe solvent was evaporated
  5. customthe obtained crude product
  6. additionwas treated in the same manner as in step 3 in Example 1

Sources & evidence

ORD record
ord-27f52530310940de99e9f26385f32395
Source dataset
uspto-grants-2004_11
Patent number
US06825191B2

Reaction notes

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