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

HRID 1398294Notes

Reaction equation

HRID 1398294 reaction equation
[Br:1][C:2]1[C:17]([O:18][CH2:19][C@@H:20]([NH:25]C(=O)OC(C)(C)C)[CH2:21][CH:22]([CH3:24])[CH3:23])=[CH:16][C:5]2[N:6]([CH3:15])[C:7](=[O:14])[C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[N:10][CH:9]=3.Cl.O1CCOCC1>CO>[NH2:25][C@@H:20]([CH2:21][CH:22]([CH3:24])[CH3:23])[CH2:19][O:18][C:17]1[C:2]([Br:1])=[CH:3][C:4]2[C:13]3[C:8](=[CH:9][N:10]=[CH:11][CH:12]=3)[C:7](=[O:14])[N:6]([CH3:15])[C:5]=2[CH:16]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86710307(S)-tert-butyl (1-((9-bromo-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

Product 1

HCID 73213655(S)-8-((2-amino-4-methylpentyl)oxy)-9-bromo-6-methylbenzo[c][2,7]naphthyridin-5(6H)-oneYield 30%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (S)-tert-butyl (1-((9-bromo-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (80 mg, 1.586 mmol) in anhydrous methanol (5 mL) was added a 4 M solution of HCl in 1,4-dioxane (2 mL, 8 mmol) dropwise at 0° C. The reaction mixture was warmed to room temperature and stirred for 2 h. The mixture was then was concentrated under reduced pressure to afford crude product which was purified by preparative HPLC (10 mM ammonium acetate in water; acetonitrile) to afford (S)-8-((2-amino-4-methylpentyl)oxy)-9-bromo-6-methylbenzo[c][2,7]naphthyridin-5(6H)-one (20 mg, 0.049 mmol, 30% yield) as an off-white solid. LC/MS (ESI) m/e 404.1 [(M+H)+, calcd for C19H23BrN3O2 404.1]; LC/MS retention time (method A): tR=1.47 min; HPLC retention time (method A): tR=9.55 min; HPLC retention time (method B): tR=10.23 min; 1H NMR (400 MHz, CD3OD) δ ppm 9.48 (s, 1H), 8.80 (d, J=5.77 Hz, 1H), 8.67 (s, 1H), 8.26 (d, J=5.77 Hz, 1H), 7.15 (s, 1H), 4.37 (dd, J=9.54, 3.76 Hz, 1H), 4.18 (dd, J=9.66, 6.40 Hz, 1H), 3.83 (s, 3H), 3.48-3.56 (m, 1H), 1.89 (m, 1H), 1.51-1.72 (m, 2H), 1.05 (t, J=6.27 Hz, 6H).

Workup

  1. concentrationThe mixture was then was concentrated under reduced pressure
  2. customto afford crude product which
  3. customwas purified by preparative HPLC (10 mM ammonium acetate in water; acetonitrile)

Sources & evidence

ORD record
ord-0d5c9bdd854342c4bf9006cf2a3e2578
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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