Trimethyl orthovalerate → 1,1-dimethylethyl N-[4-(2-butyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butyl]carbamate

HRID 636605Notes

Reaction equation

HRID 636605 reaction equation
[C:1](OC)(OC)(OC)[CH2:2][CH2:3][CH2:4][CH3:5].[NH2:12][C:13]1[CH:14]=[N:15][C:16]2[C:21]([C:22]=1[NH:23][CH2:24][CH2:25][CH2:26][CH2:27][NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[N:20][CH:19]=[CH:18][CH:17]=2.O.C1(C)C=CC(S(OS(C2C=CC(C)=CC=2)(=O)=O)(=O)=O)=CC=1>C1(C)C(C)=CC=CC=1.C(OCC)(=O)C>[CH2:2]([C:1]1[N:23]([CH2:24][CH2:25][CH2:26][CH2:27][NH:28][C:29](=[O:35])[O:30][C:31]([CH3:32])([CH3:34])[CH3:33])[C:22]2[C:21]3[N:20]=[CH:19][CH:18]=[CH:17][C:16]=3[N:15]=[CH:14][C:13]=2[N:12]=1)[CH2:3][CH2:4][CH3:5]

Participants

6

Reactant 3

HCID 83755Trimethyl orthovalerateHCID 22172729Tert-butyl 4-[(3-amino[1,5]naphthyridin-4-yl)amino]butylcarbamateHCID 22172731p-Toluene sulfonic anhydride hydrate

Product 1

HCID 221727131,1-dimethylethyl N-[4-(2-butyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butyl]carbamate

Reagents, catalysts & solvents 2

HCID 7237O-XyleneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Freshly distilled trimethyl orthovalerate (41 mL, 0.24 mole) was added to a mixture of 1,1-dimethylethyl N-{4-[(3-amino[1,5]naphthyridin-4-yl)amino]butyl}carbamate (39 g, 0.12 mole) in warm xylene (500 mL). The reaction mixture was heated at reflux overnight. Thin layer chromatography showed that at least half of the starting material was still present. p-Toluenesulfonic anhydride monohydrate (6 g) was added. After a short time thin layer chromatography showed that the reaction was complete. The reaction mixture was allowed to cool to ambient temperature and then it was diluted with ethyl acetate and washed with aqueous sodium bicarbonate. The organic layer was concentrated under vacuum to provide an oily residue. The residue was triturated with hexane to provide a dark pink solid. This solid was recrystallized from acetonitrile to provide 1,1-dimethylethyl N-[4-(2-butyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butyl]carbamate as a pale peach solid, m.p. 96.0-98.0° C. Analysis: Calculated for C22H31N5O2: % C, 66.47; % H, 7.86; % N, 17.62; Found: % C, 66.29; % H, 7.78; % N, 17.76.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux overnight
  3. washwashed with aqueous sodium bicarbonate
  4. concentrationThe organic layer was concentrated under vacuum
  5. customto provide an oily residue
  6. customThe residue was triturated with hexane
  7. customto provide a dark pink solid
  8. customThis solid was recrystallized from acetonitrile

Sources & evidence

ORD record
ord-1cb4af6731964d99a85aa3a54f94c6a2
Source dataset
uspto-grants-2001_02
Patent number
US06194425B1

Reaction notes

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