Hydrochloric Acid → (S)-6-methyl-8-((4-methyl-2-(methylamino)pentyl)oxy)benzo[c][2,7]naphthyridin-5(6H)-one

HRID 1398413Notes

Reaction equation

HRID 1398413 reaction equation
[CH3:1][N:2]([C@@H:10]([CH2:29][CH:30]([CH3:32])[CH3:31])[CH2:11][O:12][C:13]1[CH:14]=[CH:15][C:16]2[C:25]3[C:20](=[CH:21][N:22]=[CH:23][CH:24]=3)[C:19](=[O:26])[N:18]([CH3:27])[C:17]=2[CH:28]=1)C(=O)OC(C)(C)C.Cl.CCOCC>ClCCl>[CH3:27][N:18]1[C:17]2[CH:28]=[C:13]([O:12][CH2:11][C@@H:10]([NH:2][CH3:1])[CH2:29][CH:30]([CH3:32])[CH3:31])[CH:14]=[CH:15][C:16]=2[C:25]2[C:20](=[CH:21][N:22]=[CH:23][CH:24]=2)[C:19]1=[O:26]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 86710401(S)-tert-butyl methyl(4-methyl-1-((6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)pentan-2-yl)carbamate

Product 1

HCID 73214162(S)-6-methyl-8-((4-methyl-2-(methylamino)pentyl)oxy)benzo[c][2,7]naphthyridin-5(6H)-oneYield 32.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To the solution of (S)-tert-butyl methyl(4-methyl-1-((6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)pentan-2-yl)carbamate (180 mg, 0.078 mmol) in dichloromethane (4 mL) cooled to 0° C. was added HCl in ether (4 mL, 4.00 mmol) slowly over a period of 1 min. The reaction mixture was stirred at 0° C. for 5 min then warmed to room temperature and stirred for 4 h. The volatiles were then removed under reduced pressure. The residue was purified via reverse phase HPLC (0.1% TFA in water:acetonitrile) to afford (S)-6-methyl-8-((4-methyl-2-(methylamino)pentyl)oxy)benzo[c][2,7]naphthyridin-5(6H)-one (15 mg, 0.025 mmol, 32% yield) as a yellow solid. LC/MS (ESI) m/e 340.2, [(M+H)+, calcd for C20H26N3O2, 340.2]; LC/MS retention time (method I): tR=1.6 min. HPLC retention time (method A): tR=7.59 min; HPLC retention time (method B): tR=8.08 min. 1H NMR (400 MHz, METHANOL-d4) δ ppm 9.54 (s, 1H), 8.83 (d, J=5.8 Hz, 1H), 8.53 (d, J=8.8 Hz, 1H), 8.46 (d, J=6.0 Hz, 1H), 7.27-7.16 (m, 2H), 4.57 (dd, J=11.3, 3.0 Hz, 1H), 4.44 (dd, J=11.3, 5.3 Hz, 1H), 3.84 (s, 3H), 3.78-3.68 (m, 1H), 2.84 (s, 3H), 1.95-1.78 (m, 2H), 1.75-1.61 (m, 1H), 1.08 (d, J=6.5 Hz, 6H).

Workup

  1. temperaturethen warmed to room temperature
  2. stirringstirred for 4 h
  3. customThe volatiles were then removed under reduced pressure
  4. customThe residue was purified via reverse phase HPLC (0.1% TFA in water:acetonitrile)

Sources & evidence

ORD record
ord-a5a9c31468954271b4a2f7d9c4c16297
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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