Phosphorus oxychloride → 5-Benzyloxy-4-methoxy-2-{1-[4-(morpholinecarbonyl)-1,4-diazepan-1-yl]ethylideneamino}benzonitrile

HRID 1004004Notes

Reaction equation

HRID 1004004 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].[NH2:24][C:25]1[CH:32]=[C:31]([O:33][CH3:34])[C:30]([O:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[CH:29][C:26]=1[C:27]#[N:28]>ClCCl>[CH2:36]([O:35][C:30]1[C:31]([O:33][CH3:34])=[CH:32][C:25]([N:24]=[C:6]([N:9]2[CH2:15][CH2:14][CH2:13][N:12]([C:16]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[O:17])[CH2:11][CH2:10]2)[CH3:7])=[C:26]([CH:29]=1)[C:27]#[N:28])[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 110759942-Amino-5-(benzyloxy)-4-methoxybenzonitrileHCID 155382861-Acetyl-4-(4-morpholinecarbonyl)-1,4-diazepane

Product 1

HCID 536525885-Benzyloxy-4-methoxy-2-{1-[4-(morpholinecarbonyl)-1,4-diazepan-1-yl]ethylideneamino}benzonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Phosphorous oxychloride (0.81 ml, 0.0086 mol) was added to a solution of 1-acetyl-4-(4-morpholinecarbonyl)-1,4-diazepane (4.02 g, 0.0157 mol) in dichloromethane (25 ml) and the mixture stirred for 30 minutes at room temperature. A solution of 2-amino-5-benzyloxy-4-methoxybenzonitrile (2 g, 0.0078 mol) in dichloromethane (25 ml) was then added and the reaction stirred for 18 hours at 40° C. On cooling, the reaction mixture was poured carefully in to ice/water (100 ml) and extracted with dichloromethane (2×100 ml). The combined organic layers were dried (MgSO4), filtered and evaporated under reduced pressure to give a brown oil. The crude product was purified on silica gel eluting with a solvent gradient of methanol:dichloromethane (2:98 to 10:90 v/v) to give the subtitle compound. Rf 0.67 (0.880 aqueous ammonia:methanol:dichloromethane 1:7:92, v/v). MS m/z 492 (MH)+.

Workup

  1. stirringthe reaction stirred for 18 hours at 40° C
  2. temperatureOn cooling
  3. extractionextracted with dichloromethane (2×100 ml)
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customto give a brown oil
  8. customThe crude product was purified on silica gel eluting with a solvent gradient of methanol:dichloromethane (2:98 to 10:90 v/v)

Sources & evidence

ORD record
ord-d8aaa0f43adb45a0b7c0fecc857d8356
Source dataset
uspto-grants-2000_04
Patent number
US06048864

Reaction notes

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