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

HRID 1398340Notes

Reaction equation

HRID 1398340 reaction equation
[CH3:1][C:2]1[N:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[N:9]([CH3:13])[C:8]1[CH:14]=[C:15]([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]=[CH:17][C:7]2=1.Cl>CO>[NH2:25][C@@H:20]([CH2:21][CH:22]([CH3:24])[CH3:23])[CH2:19][O:18][C:15]1[CH:16]=[CH:17][C:7]2[C:6]3[C:11](=[C:2]([CH3:1])[N:3]=[CH:4][CH:5]=3)[C:10](=[O:12])[N:9]([CH3:13])[C:8]=2[CH:14]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86710338(S)-tert-butyl (1-((4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

Product 1

HCID 73213798(S)-8-((2-amino-4-methylpentyl)oxy)-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-oneYield 31%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (S)-tert-butyl (1-((4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (30 mg, 0.068 mmol) in MeOH (3 mL) at 0° C. was added HCl (4N in 1,4-dioxane, 3 mL, 12.00 mmol). The solution was warmed to room temperature and stirred for 2 h. The reaction mixture was then concentrated under reduced pressure and the residue dissolved in ethyl acetate (10 mL). The organic layer was washed with saturated NaHCO3 (2×10 mL) and water (20 mL); dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by preparative TLC (DCM-MeOH mixture) to afford (S)-8-((2-amino-4-methylpentyl)oxy)-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (8 mg, 0.021 mmol, 31% yield) as a brown solid. LC/MS, (ESI) m/z 340.2 [(M+H)+, calcd for C20H26N3O2, 340.2]; LC/MS retention time (method B): tR=1.27 min. HPLC retention time (method A): tR=8.30 and HPLC retention time (method B): tR=8.97 min. 1H NMR (400 MHz, CD3OD) δ ppm 8.53 (d, J=5.77 Hz, 1H), 8.33 (d, J=9.54 Hz, 1H), 8.08 (d, J=5.77 Hz, 1H), 7.00-7.06 (m, 2H), 4.21 (m, 1H), 4.02 (m, 1H), 3.73 (s, 3H), 3.47-3.52 (m, 1H), 3.06 (s, 3H), 1.82-1.93 (m, 1H), 1.67-1.76 (m, 2H), 1.26-1.56 (m, 6H).

Workup

  1. concentrationThe reaction mixture was then concentrated under reduced pressure
  2. dissolutionthe residue dissolved in ethyl acetate (10 mL)
  3. washThe organic layer was washed with saturated NaHCO3 (2×10 mL) and water (20 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by preparative TLC (DCM-MeOH mixture)

Sources & evidence

ORD record
ord-e348f3453cad4ffe94c9a65069c734eb
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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