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

HRID 1398314Notes

Reaction equation

HRID 1398314 reaction equation
[CH2:1]([N:8]1[C:17]2[CH:18]=[C:19]([O:22][CH2:23][C@@H:24]([NH:29]C(=O)OC(C)(C)C)[CH2:25][CH:26]([CH3:28])[CH3:27])[CH:20]=[CH:21][C:16]=2[C:15]2[C:10](=[CH:11][N:12]=[CH:13][CH:14]=2)[C:9]1=[O:37])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.C(OCC)C>ClCCl>[NH2:29][C@@H:24]([CH2:25][CH:26]([CH3:28])[CH3:27])[CH2:23][O:22][C:19]1[CH:20]=[CH:21][C:16]2[C:15]3[C:10](=[CH:11][N:12]=[CH:13][CH:14]=3)[C:9](=[O:37])[N:8]([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C:17]=2[CH:18]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 86710320(S)-tert-butyl (1-((6-benzyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

Product 1

HCID 73213730(S)-8-((2-amino-4-methylpentyl)oxy)-6-benzylbenzo[c][2,7]naphthyridin-5(6H)-oneYield 35%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-tert-butyl (1-((6-benzyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (35 mg, 0.070 mmol) in anhydrous dichloromethane (1 mL) was added a 2 M solution of HCl in diethyl ether (0.17 mL, 0.349 mmol) dropwise at 0° C. The reaction mixture was allowed to warm to room temperature and stirred for 2 h. The reaction mixture was then concentrated under reduced pressure to afford crude product which was purified by preparative TLC (ethyl acetate in petroleum ether) to afford (S)-8-((2-amino-4-methylpentyl)oxy)-6-benzylbenzo[c][2,7]naphthyridin-5(6H)-one (10 mg, 0.024 mmol, 35% yield) as a light yellow solid. LC/MS (ESI) m/e 402.2 [(M+H)+, calcd for C25H28N3O2 402.2]; LC/MS retention time (method C): tR=1.77 min; HPLC retention time (method A): tR=5.54 min; HPLC retention time (method B): tR=6.17 min. 1H NMR (400 MHz CD3OD) δ ppm 9.61 (br. s., 1H), 8.87 (d, J=4.52 Hz, 1H), 8.53 (d, J=9.04 Hz, 1H), 8.47 (d, J=6.02 Hz, 1H), 7.28-7.38 (m, 5H), 7.15 (dd, J=8.91, 2.38 Hz, 1H), 7.04 (d, J=2.26 Hz, 1H), 5.72 (d, J=5.77 Hz, 2H), 4.27 (dd, J=10.54, 3.26 Hz, 1H), 4.10 (dd, J=10.42, 6.40 Hz, 1H), 3.69 (dd, J=6.65, 3.14 Hz, 1H), 1.68-1.81 (m, 1H), 1.57-1.67 (m, 2H), 1.00-1.05 (m, 6H).

Workup

  1. concentrationThe reaction mixture was then concentrated under reduced pressure
  2. customto afford crude product which
  3. customwas purified by preparative TLC (ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-e028ae61064c457ebdba9e7963636f5b
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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