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

HRID 1398319Notes

Reaction equation

HRID 1398319 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][N:5]1[C:14]2[CH:15]=[C:16]([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]=[CH:18][C:13]=2[C:12]2[C:7](=[CH:8][N:9]=[CH:10][CH:11]=2)[C:6]1=[O:34].Cl.O1CCOCC1>CO>[NH2:26][C@@H:21]([CH2:22][CH:23]([CH3:25])[CH3:24])[CH2:20][O:19][C:16]1[CH:17]=[CH:18][C:13]2[C:12]3[C:7](=[CH:8][N:9]=[CH:10][CH:11]=3)[C:6](=[O:34])[N:5]([CH2:4][CH2:3][O:2][CH3:1])[C:14]=2[CH:15]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86710324(S)-tert-butyl (1-((6-(2-methoxyethyl)-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

Product 1

HCID 73213795(S)-8-((2-amino-4-methylpentyl)oxy)-6-(2-methoxyethyl)benzo[c][2,7]naphthyridin-5(6H)-oneYield 32%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (S)-tert-butyl (1-((6-(2-methoxyethyl)-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (0.080 g, 0.170 mmol) in anhydrous methanol (5 mL) was added a 4M solution of HCl in 1,4-dioxane (0.21 mL, 0.85 mmol) dropwise at 0° C. The reaction mixture was allowed to warm to room temperature and stirred for 2 h. The reaction mixture was concentrated under reduced pressure to afford crude compound which was purified by preparative HPLC (10 mM ammonium acetate in water:acetonitrile) to afford (S)-8-((2-amino-4-methylpentyl)oxy)-6-(2-methoxyethyl)benzo[c][2,7]naphthyridin-5(6H)-one (20 mg, 0.054 mmol, 32% yield) a white solid. LC/MS (ESI) m/e 370.2 [(M+H)+, calcd for C21H28N3O3 370.2]; LC/MS retention time (method A): tR=1.34 min; HPLC retention time (method A): tR=8.36 min; HPLC retention time (method B): tR=8.78 min. 1H NMR (400 MHz, CD3OD) δ ppm 9.45 (s, 1H), 8.76 (d, J=5.77 Hz, 1H), 8.40 (d, J=9.03 Hz, 1H,), 8.23 (d, J=6.02 Hz, 1H), 7.29 (d, J=2.26 Hz, 1H), 7.11 (d, J=8.78 Hz, 1H), 4.61 (t, J=5.65 Hz, 2H), 4.36 (s, 1H), 4.20 (s, 1H), 3.81 (t, J=5.77 Hz, 2H), 3.63-3.71 (m, 1H), 3.37 (s, 3H), 1.86 (m, 1H), 1.67 (qt, J=14.01, 7.09 Hz, 2H), 1.06 (d, J=5.77 Hz, 6H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customto afford crude compound which
  3. customwas purified by preparative HPLC (10 mM ammonium acetate in water:acetonitrile)

Sources & evidence

ORD record
ord-cadcd992ad5944f1a91cabc357e4c42c
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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