Ethanol → 1,1-dimethylethyl N-[4-(1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butyl]carbamate

HRID 47516Notes

Reaction equation

HRID 47516 reaction equation
[CH2:1](OC(OCC)OCC)C.[NH2:11][C:12]1[CH:13]=[N:14][C:15]2[C:20]([C:21]=1[NH:22][CH2:23][CH2:24][CH2:25][CH2:26][NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[N:19][CH:18]=[CH:17][CH:16]=2.C(O)C.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[N:22]1([CH2:23][CH2:24][CH2:25][CH2:26][NH:27][C:28](=[O:34])[O:29][C:30]([CH3:31])([CH3:33])[CH3:32])[C:21]2[C:20]3[N:19]=[CH:18][CH:17]=[CH:16][C:15]=3[N:14]=[CH:13][C:12]=2[N:11]=[CH:1]1

Participants

6

Reactant 4

HCID 702EthanolHCID 6101p-Toluenesulfonic acidHCID 31214Ethyl orthoformateHCID 22172729Tert-butyl 4-[(3-amino[1,5]naphthyridin-4-yl)amino]butylcarbamate

Product 1

HCID 221727151,1-dimethylethyl N-[4-(1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butyl]carbamateYield 21.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Triethylorthoformate (2.8 mL, 16.6 mmol) was added to a solution of 1,1-dimethylethyl N-{4-[(3-amino[1,5]naphthyridin-4-yl)amino]butyl}carbamate (5.0 g, 15.1 mmol) in toluene (150 mL). The reaction was heated at reflux overnight with ethanol being collected in a Dean Stark trap. The reaction mixture was heated at reflux for an additional 6 hours and then p-toluenesulfonic acid (1.4 g, 7.5 mmol) was added and the reaction was refluxed overnight. A dark orange/brown oil had formed. The toluene supernatant was decanted off and concentrated under vacuum to provide 1.1 g of 1,1-dimethylethyl N-[4-(1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butyl]carbamate. The oil was identified as 4-(1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butaneamine. This material was reacted with 1,1-dimethylethyl-dicarbonate to provide an additional 1 g of 1,1-dimethylethyl N-[4-(1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butyl]carbamate. The two lots were combined and carried on to the next step.

Workup

  1. temperatureThe reaction was heated
  2. customcollected in a Dean Stark trap
  3. temperatureThe reaction mixture was heated
  4. temperatureat reflux for an additional 6 hours
  5. temperaturethe reaction was refluxed overnight
  6. customA dark orange/brown oil had formed
  7. customThe toluene supernatant was decanted off
  8. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-94e84b5c878a4fdb94ee4a94896b9883
Source dataset
uspto-grants-2004_03
Patent number
US06699878B2

Reaction notes

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