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 1004029Notes

Reaction equation

HRID 1004029 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-159ca9ddf0404675b489a64d9cf933f2
Source dataset
uspto-grants-2000_04
Patent number
US06048864

Reaction notes

Loading…