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

HRID 1398292Notes

Reaction equation

HRID 1398292 reaction equation
[CH3:1][CH:2]([CH3:31])[CH2:3][C@H:4]([NH:23]C(=O)OC(C)(C)C)[CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]2[C:19]3[C:14](=[CH:15][N:16]=[CH:17][CH:18]=3)[C:13](=[O:20])[N:12]([CH3:21])[C:11]=2[CH:22]=1.Cl>ClCCl.O1CCOCC1>[NH2:23][C@@H:4]([CH2:3][CH:2]([CH3:31])[CH3:1])[CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]2[C:19]3[C:14](=[CH:15][N:16]=[CH:17][CH:18]=3)[C:13](=[O:20])[N:12]([CH3:21])[C:11]=2[CH:22]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 86710306(S)-tert-butyl (4-methyl-1-((6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)pentan-2-yl)carbamate

Product 1

HCID 73213654(S)-8-((2-amino-4-methylpentyl)oxy)-6-methylbenzo[c][2,7]naphthyridin-5(6H)-oneYield 35.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (S)-tert-butyl (4-methyl-1-((6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)pentan-2-yl)carbamate (190 mg, 0.447 mmol) in dichloromethane (4 mL) at 0° C. was added hydrogen chloride (81 mg, 0.558 mL, 2.233 mmol) in 1,4-dioxane (4 M) dropwise and the reaction mixture was stirred at 0° C. for 30 min then warmed to room temperature and allowed to stir for 2 h. The solvents were removed under reduced pressure to afford crude product which was purified by preparative HPLC (0.1% TFA in water) to afford (S)-8-((2-amino-4-methylpentyl)oxy)-6-methylbenzo[c][2,7]naphthyridin-5(6H)-one (51 mg, 0.157 mmol, 35% yield) as a yellow solid. LC/MS (ESI) m/e 326.2 [(M+H)+, calcd for C19H24N3O2 326.2]; LC/MS retention time (method A): tR=1.21 min; HPLC retention time (method A): tR=7.39 min; HPLC retention time (method B): tR=7.40 min. 1H NMR (400 MHz, CD3OD) δ ppm 9.48 (s, 1H), 8.77 (d, J=5.77 Hz, 1H), 8.43 (d, J=8.78 Hz, 1H), 8.26 (d, J=5.77 Hz, 1H), 7.09-7.16 (m, 2H), 4.20 (dd, J=9.41, 3.89 Hz, 1H), 4.02 (dd, J=9.29, 7.03 Hz, 1H), 3.81 (s, 3H), 3.35-3.39 (m, 1H), 1.81-1.91 (m, 1H), 1.41-1.56 (m, 2H), 0.98-1.05 (m, 6H).

Workup

  1. temperaturethen warmed to room temperature
  2. stirringto stir for 2 h
  3. customThe solvents were removed under reduced pressure
  4. customto afford crude product which
  5. customwas purified by preparative HPLC (0.1% TFA in water)

Sources & evidence

ORD record
ord-9f0b8f4c9f8d47f6a3b9f287f8829496
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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