(2S)-5-oxooxolane-2-carboxylic acid → N-[2-(4-Amino-2-butyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)ethyl]-5-oxotetrahydro-2-furancarboxamide

HRID 497789

Reaction equation

HRID 497789 reaction equation
[O:1]=[C:2]1[O:6][C@H:5]([C:7]([OH:9])=O)[CH2:4][CH2:3]1.[NH2:10][C:11]1[C:20]2[N:21]=[C:22]([CH2:27][CH2:28][CH2:29][CH3:30])[N:23]([CH2:24][CH2:25][NH2:26])[C:19]=2[C:18]2[N:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N:12]=1.Cl.CON(OC)CCCN=C=NCC>ClCCl>[NH2:10][C:11]1[C:20]2[N:21]=[C:22]([CH2:27][CH2:28][CH2:29][CH3:30])[N:23]([CH2:24][CH2:25][NH:26][C:7]([CH:5]3[CH2:4][CH2:3][C:2](=[O:1])[O:6]3)=[O:9])[C:19]=2[C:18]2[N:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N:12]=1

Participants

5

Reactant 3

HCID 636468(2S)-5-oxooxolane-2-carboxylic acidHCID 219460272-(4-amino-2-butyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)ethaneamineHCID 219844591-(3-Dimethoxyaminopropyl)-3-ethylcarbodiimide hydrochloride

Product 1

HCID 22172717N-[2-(4-Amino-2-butyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)ethyl]-5-oxotetrahydro-2-furancarboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of (S)-(+)-5-oxo-2-tetrahydrofurancarboxylic acid (0.23 g, 1.7 mmole in anhydrous dichloromethane (30 mL) was slowly added to a solution of 2-(4-amino-2-butyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)ethaneamine (0.5 g, 1.7 mmol) in anhydrous dichloromethane (100 mL). The reaction mixture was stirred at ambient temperature for 30 minutes and then a solution of 1-[3-(dimethoxyamino)propyl]-3-ethylcarbodiimide hydrochloride (0.37 g, 1.9 mmol) in anhydrous dichloromethane (50 mL) was added dropwise. The reaction mixture was stirred at ambient temperature overnight and then filtered to remove solids. The filtrate was washed twice with 10% sodium hydroxide and then with brine, dried, and then concentrated under vacuum to provide 0.3 g of crude product. This material was purified by column chromatography (silica gel eluting with dichloromethane) followed by recrystallization from acetonitrile to provide 0.1 g of N-[2-(4-amino-2-butyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)ethyl]-5-oxotetrahydro-2-furancarboxamide as a white powder, m.p. 153-154° C. Analysis: Calculated for C20H24N6O3: %C, 60.59; %H, 6.10; %N, 21.19; Found: %C, 60.34; %H, 6.14; %N, 21.13. HRMS (EI) calcd for C20H24N6O3 (M+) 396.1909 found 396.1905.

Workup

  1. stirringThe reaction mixture was stirred at ambient temperature overnight
  2. filtrationfiltered
  3. customto remove solids
  4. washThe filtrate was washed twice with 10% sodium hydroxide
  5. dry with materialwith brine, dried
  6. concentrationconcentrated under vacuum
  7. customto provide 0.3 g of crude product
  8. customThis material was purified by column chromatography (silica gel eluting with dichloromethane)
  9. customfollowed by recrystallization from acetonitrile

Sources & evidence

ORD record
ord-6dbd3d7481604983acb8a505757c4a96
Source dataset
uspto-grants-2005_09
Patent number
US06949646B2

Linked notes

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