Hydrochloric Acid → (S)-8-((2-amino-4-methylpentyl)oxy)-6,9-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one

HRID 1398296Notes

Reaction equation

HRID 1398296 reaction equation
[CH3:1][N:2]1[C:11]2[CH:12]=[C:13]([O:17][CH2:18][C@@H:19]([NH:24]C(=O)OC(C)(C)C)[CH2:20][CH:21]([CH3:23])[CH3:22])[C:14]([CH3:16])=[CH:15][C:10]=2[C:9]2[C:4](=[CH:5][N:6]=[CH:7][CH:8]=2)[C:3]1=[O:32].Cl.O1CCOCC1>CO>[NH2:24][C@@H:19]([CH2:20][CH:21]([CH3:23])[CH3:22])[CH2:18][O:17][C:13]1[C:14]([CH3:16])=[CH:15][C:10]2[C:9]3[C:4](=[CH:5][N:6]=[CH:7][CH:8]=3)[C:3](=[O:32])[N:2]([CH3:1])[C:11]=2[CH:12]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86710308(S)-tert-butyl (1-((6,9-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

Product 1

HCID 73213656(S)-8-((2-amino-4-methylpentyl)oxy)-6,9-dimethylbenzo[c][2,7]naphthyridin-5(6H)-oneYield 49.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

In a 25 mL round-bottomed flask, (S)-tert-butyl (1-((6,9-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (80 mg, 0.182 mmol) was taken in MeOH (6 mL). The reaction mixture was cooled to 0° C. and a 4M solution of HCl in 1,4-dioxane (3.75 mL, 12 mmol) was added and the mixture stirred at RT for 2 h. The MeOH was removed and the crude product was dissolved in ethyl acetate (20 mL). The ethyl acetate layer was washed with water (10 mL) and dried over sodium sulfate. Removal of the solvent gave crude product which was purified by silica-gel column (MeOH—CHCl3 mixture) to afford (S)-8-((2-amino-4-methylpentyl)oxy)-6,9-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (0.03 g, 0.09 mmol, 49% yield) as yellow solid. LC/MS (ESI) m/e 340.2 [(M+H)+, calcd for C20H26N3O2, 340.4]; LC/MS retention time (method B): tR=1.33 min. HPLC retention time (method A): tR=8.58 min; HPLC retention time (method B): tR=8.12 min. 1H NMR (400 MHz, CD3OD) δ ppm 9.51 (s, 1H), 8.79 (d, J=6.02 Hz, 1H), 8.40 (d, J=5.77 Hz, 1H), 8.33 (s, 1H), 7.10 (s, 1H), 4.50 (dd, J=10.67, 3.14 Hz, 1H), 4.36 (dd, J=10.67, 5.90 Hz, 1H), 3.77-3.87 (m, 4H), 2.46 (s, 3H), 1.79-1.92 (m, 2H), 1.66-1.77 (m, 1H), 1.08 (dd, J=6.27, 4.02 Hz, 6H).

Workup

  1. customThe MeOH was removed
  2. dissolutionthe crude product was dissolved in ethyl acetate (20 mL)
  3. washThe ethyl acetate layer was washed with water (10 mL)
  4. dry with materialdried over sodium sulfate
  5. customRemoval of the solvent
  6. customgave crude product which
  7. customwas purified by silica-gel column (MeOH—CHCl3 mixture)

Sources & evidence

ORD record
ord-1780fd06ce714c68b8df4f2feb8de0a9
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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