Sodium Hydroxide → 2-Cyclobutyloxy-3,4-dimethoxy-6-{1-[4-(morpholinecarbonyl)-1,4-diazepan-1-yl]ethylideneamino}benzonitrile

HRID 1004022Notes

Reaction equation

HRID 1004022 reaction equation
P(Cl)(Cl)(Cl)=O.[C:6]([N:9]1[CH2:15][CH2:14][CH2:13][N:12]([C:16]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[O:17])[CH2:11][CH2:10]1)(=O)[CH3:7].[C:24]([C:26]1[C:32]([O:33][CH:34]2[CH2:37][CH2:36][CH2:35]2)=[C:31]([O:38][CH3:39])[C:30]([O:40][CH3:41])=[CH:29][C:27]=1[NH2:28])#[N:25].[OH-].[Na+]>ClCCl.O>[NH3:9].[CH:34]1([O:33][C:32]2[C:31]([O:38][CH3:39])=[C:30]([O:40][CH3:41])[CH:29]=[C:27]([N:28]=[C:6]([N:9]3[CH2:15][CH2:14][CH2:13][N:12]([C:16]([N:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)=[O:17])[CH2:11][CH2:10]3)[CH3:7])[C:26]=2[C:24]#[N:25])[CH2:35][CH2:36][CH2:37]1

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 155382861-Acetyl-4-(4-morpholinecarbonyl)-1,4-diazepaneHCID 184706542-Cyano-3-cyclobutyloxy-4,5-dimethoxyaniline

Product 2

HCID 222AmmoniaHCID 177736302-Cyclobutyloxy-3,4-dimethoxy-6-{1-[4-(morpholinecarbonyl)-1,4-diazepan-1-yl]ethylideneamino}benzonitrileYield 97.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Phosphorous oxychloride (210 μl, 0.0022 mol) was added to a solution of 1-acetyl-4-(4-morpholinecarbonyl)-1,4-diazepane (1.02 g, 0.0040 mol) in dichloromethane (10 ml) and the solution stirred at room temperature for 1 hour. 2-Cyano-3-cyclobutyloxy-4,5-dimethoxyaniline (500 mg, 0.002 mol) was then added and the reaction stirred at reflux under a nitrogen atmosphere for 18 hours. On cooling, water (30 ml) and aqueous sodium hydroxide solution were added and the mixture extracted with dichloromethane (2×100 ml). The combined organic extracts were dried (MgSO4), filtered and evaporated under reduced pressure. The crude product was purified on silica gel eluting with dichloromethane:methanol:0.880 aqueous ammonia solution (96:3.5:0.5 v/v) to give the subtitle compound as a gum (950 mg, 97%). Rf 0.62 (dichloromethane:methanol:0.880 aqueous ammonia 92:7:1, v/v). MS m/z 486 (MH)+.

Workup

  1. stirringthe reaction stirred
  2. temperatureat reflux under a nitrogen atmosphere for 18 hours
  3. temperatureOn cooling
  4. extractionthe mixture extracted with dichloromethane (2×100 ml)
  5. dry with materialThe combined organic extracts were dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe crude product was purified on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-20ff11b0f8824bf28692c67b6373e52e
Source dataset
uspto-grants-2000_04
Patent number
US06048864

Reaction notes

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