1-Acetyl-4-(4-morpholinecarbonyl)-1,4-diazepane → 2-(2,2,2-Trifluoroethoxy)-4-methoxy-6-{1-[4-(morpholinecarbonyl)-1,4-diazepan-1-yl]ethylideneamino}benzonitrile

HRID 2228517Notes

Reaction equation

HRID 2228517 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([O:16][CH3:17])[CH:5]=[C:6]([O:10][CH2:11][C:12]([F:15])([F:14])[F:13])[C:7]=1[C:8]#[N:9].[C:18]([N:21]1[CH2:27][CH2:26][CH2:25][N:24]([C:28]([N:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)=[O:29])[CH2:23][CH2:22]1)(=O)[CH3:19]>>[F:13][C:12]([F:14])([F:15])[CH2:11][O:10][C:6]1[CH:5]=[C:4]([O:16][CH3:17])[CH:3]=[C:2]([N:1]=[C:18]([N:21]2[CH2:27][CH2:26][CH2:25][N:24]([C:28]([N:30]3[CH2:31][CH2:32][O:33][CH2:34][CH2:35]3)=[O:29])[CH2:23][CH2:22]2)[CH3:19])[C:7]=1[C:8]#[N:9]

Participants

3

Reactant 2

HCID 155382861-Acetyl-4-(4-morpholinecarbonyl)-1,4-diazepaneHCID 184706143-Amino-4-cyano-5-(2,2,2-trifluoroethoxy)anisole

Product 1

HCID 177736282-(2,2,2-Trifluoroethoxy)-4-methoxy-6-{1-[4-(morpholinecarbonyl)-1,4-diazepan-1-yl]ethylideneamino}benzonitrileYield 95%

Procedure

The subtitle compound was prepared from 3-amino-4-cyano-5-(2,2,2-trifluoroethoxy)-anisole and 1-acetyl-4-(4-morpholinecarbonyl)-1,4-diazepane following a similar procedure to that described in Example 10(g) allowing the reaction to stir for 60 hours at room temperature. The crude product was purified on silica gel eluting with a solvent gradient of dichloromethane:methanol (100:0 to 95:5, v/v). The product was dissolved in a minimum volume of dichloromethane and an excess of ethereal hydrogen chloride added. The resulting precipitate was filtered off and partitioned between saturated aqueous sodium hydroxide solution (100 ml ) and dichloromethane (200 ml). The organic layer was dried (MgSO4) and evaporated under reduced pressure to give the subtitle compound (1.83 g, 95%). Rf 0.58 (dichloromethane:methanol:0.880 aqueous ammonia 92:7:1, v/v). MS m/z 484 (MH)+.

Workup

  1. customthe reaction
  2. customThe crude product was purified on silica gel eluting with a solvent gradient of dichloromethane:methanol (100:0 to 95:5
  3. dissolutionThe product was dissolved in a minimum volume of dichloromethane
  4. additionan excess of ethereal hydrogen chloride added
  5. filtrationThe resulting precipitate was filtered off
  6. custompartitioned between saturated aqueous sodium hydroxide solution (100 ml ) and dichloromethane (200 ml)
  7. dry with materialThe organic layer was dried (MgSO4)
  8. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-b0ee0e6770694b9c9fc455eabf9a50c4
Source dataset
uspto-grants-2002_07
Patent number
US06417194B1

Reaction notes

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