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

HRID 1398430Notes

Reaction equation

HRID 1398430 reaction equation
Br[C:2]1[C:18]([O:19][CH2:20][C@@H:21]([NH:26]C(=O)OC(C)(C)C)[CH2:22][CH:23]([CH3:25])[CH3:24])=[CH:17][C:5]2[N:6]([CH3:16])[C:7](=[O:15])[C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][C:11]([CH3:14])=[N:10][CH:9]=3.Cl.O1CCOCC1>CO>[NH2:26][C@@H:21]([CH2:22][CH:23]([CH3:25])[CH3:24])[CH2:20][O:19][C:18]1[CH:2]=[CH:3][C:4]2[C:13]3[C:8](=[CH:9][N:10]=[C:11]([CH3:14])[CH:12]=3)[C:7](=[O:15])[N:6]([CH3:16])[C:5]=2[CH:17]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86710416(S)-tert-butyl (1-((9-bromo-2,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

Product 1

HCID 73214295(S)-8-((2-amino-4-methylpentyl)oxy)-2,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-oneYield 24.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (S)-tert-butyl (1-((9-bromo-2,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (30 mg, 0.058 mmol) in MeOH (3 mL) at 0° C. was added 4M HCl in 1,4-dioxane (0.362 mL, 1.447 mmol). The reaction mixture was stirred at 0° C. for 2 h. The reaction mixture was concentrated under reduced pressure to afford crude product which was purified by preparative HPLC to afford (S)-8-((2-amino-4-methylpentyl)oxy)-2,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (6 mg, 0.014 mmol, 24% yield) as an off-white solid. LC/MS (ESI) m/e 418.0 [(M+H)+, calcd for C20H25BrN3O2 418.1]; LC/MS retention time (method H): tR=1.70 min; HPLC retention time (method A): tR=6.33 min; HPLC retention time (method B): tR=7.19 min. 1H NMR (400 MHz, METHANOL-d4) δ ppm 9.31 (s, 1H), 9.28-9.33 (m, 1H), 8.58 (s, 1H), 8.08 (s, 1H), 7.09 (s, 1H), 4.42 (dd, J=9.79, 3.26 Hz, 1H), 4.25 (dd, J=9.91, 6.15 Hz, 1H), 3.78 (s, 3H), 3.63 (br. s., 1H), 2.73 (s, 3H), 2.00 (br. s., 4H), 1.85-1.92 (m, 1H), 1.71-1.80 (m, 1H), 1.57-1.66 (m, 1H), 1.06 (dd, J=6.40, 4.64 Hz, 6H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customto afford crude product which
  3. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-40fddf2dc4254d7fb5b9a01d78b152f2
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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