Dichloromethane → N3-[4-(4-amino-2-butyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butyl]nicotinamide

HRID 47484Notes

Reaction equation

HRID 47484 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][CH2:21][CH2:22][CH3:23])[N:14]([CH2:15][CH2:16][CH2:17][CH2:18][NH2:19])[C:10]=2[C:9]2[N:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1.C(N(CC)C(C)C)(C)C.Cl.[C:34](Cl)(=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[N:37][CH:36]=1.ClCCl>O1CCCC1.CO>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][CH2:21][CH2:22][CH3:23])[N:14]([CH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:34](=[O:41])[C:35]3[CH:40]=[CH:39][CH:38]=[N:37][CH:36]=3)[C:10]=2[C:9]2[N:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 81531DiisopropylethylamineHCID 884383-Pyridinecarbonyl chloride, hydrochloride (1:1)HCID 129926164-(4-amino-2-butyl 1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butaneamine

Product 1

HCID 12987864N3-[4-(4-amino-2-butyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butyl]nicotinamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-(4-Amino-2-butyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butaneamine (0.050 g, 0.16 mmol) was suspended in tetrahydrofuran (30 mL). N,N-diisopropylethylamine (28 μL, 0.16 mmol) was added to the suspension and then nicotinoyl chloride hydrochloride (0.028 g, 0.16 mmol) was added. The reaction mixture was stirred at ambient temperature for 1 hour by which time a solution was obtained. Thin layer chromatography (9:1 dichloromethane:methanol) showed one major new spot with a higher Rf and only a trace of starting material. Aminomethyl resin (100 mg) was added and the reaction mixture was stirred for 5 minutes. The solvent was removed under vacuum. The residue was dissolved in dichloromethane and placed on a layer of silica gel. The silica gel was eluted first with dichloromethane and then with 9:1 dichloromethane:methanol. The cleanest fractions were combined and then concentrated under vacuum to provide N3-[4-(4-amino-2-butyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)butyl]nicotinamide as a white powder. 1H NMR (300 MHz, CDCl3) δ 8.91 (m, 1 H), 8.68 (d, J=4.5 Hz, 1 H), 8.45 (d, J=4.3 Hz, 1 H), 8.03 (m, 2 H), 7.30-7.40 (m, 2 H), 6.98 (s, 2 H), 5.51 (s, 1 H), 4.86 (apparent t, J=7.9 Hz, 2 H), 3.66 (q, J=6.5 Hz, 2 H), 2.92 (apparent t, J=7.7 Hz, 2 H), 2.05 (m, 2 H), 1.75-1.95 (m, 4 H), 1.51 (m, 2 H), 1.00 (t, J=7.3 Hz, 3 H); HRMS (EI) calcd for C23H27N7O (M+) 417.2277, found 417.2276.

Workup

  1. customwas obtained
  2. additionAminomethyl resin (100 mg) was added
  3. stirringthe reaction mixture was stirred for 5 minutes
  4. customThe solvent was removed under vacuum
  5. dissolutionThe residue was dissolved in dichloromethane
  6. washThe silica gel was eluted first with dichloromethane
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-0344f44de0754b4394af20918d342649
Source dataset
uspto-grants-2004_03
Patent number
US06699878B2

Reaction notes

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