Hydrochloric Acid → (S)-8-((2-amino-4-methylpentyl)oxy)-6-methyl-5-oxo-5,6 dihydrobenzo[c][2,7]naphthyridine-9-carbonitrile

HRID 1398298Notes

Reaction equation

HRID 1398298 reaction equation
[C:1]([C:3]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:6]2[N:7]([CH3:16])[C:8](=[O:15])[C:9]3[C:14]([C:5]=2[CH:4]=1)=[CH:13][CH:12]=[N:11][CH:10]=3)#[N:2].Cl.O1CCOCC1>CO>[NH2:26][C@@H:21]([CH2:22][CH:23]([CH3:25])[CH3:24])[CH2:20][O:19][C:18]1[C:3]([C:1]#[N:2])=[CH:4][C:5]2[C:14]3[C:9](=[CH:10][N:11]=[CH:12][CH:13]=3)[C:8](=[O:15])[N:7]([CH3:16])[C:6]=2[CH:17]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86710309(S)-tert-butyl (1-((9-cyano-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

Product 1

HCID 73213724(S)-8-((2-amino-4-methylpentyl)oxy)-6-methyl-5-oxo-5,6 dihydrobenzo[c][2,7]naphthyridine-9-carbonitrileYield 7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

In a 25 mL round-bottomed flask, (S)-tert-butyl (1-((9-cyano-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (75 mg, 0.167 mmol) was taken up in MeOH (4 mL) and cooled to 0° C. The mixture was treated with 4M solution of HCl in 1,4-dioxane (2 mL, 8 mmol) and stirred for 2 h at RT. The MeOH was removed and the crude product was dissolved in EtOAc (20 mL). The ethyl acetate layer was washed with water (2×10 mL) and dried over sodium sulfate. Removal of the solvent gave crude product which was purified by silica-gel column (MeOH—CHCl3 mixture) to obtain (S)-8-((2-amino-4-methylpentyl)oxy)-6-methyl-5-oxo-5,6 dihydrobenzo[c][2,7]naphthyridine-9-carbonitrile (4 mg, 0.01 mmol, 7% yield over 2 steps) as a yellow solid. LC/MS (ESI) m/e 351.2. [(M+H)+, calcd for C20H23N4O2, 351.4]; LC/MS retention time (method B): tR=1.43 min. HPLC retention time (method A): tR=9.69 min; HPLC retention time (method B): tR=9.31 min. 1H NMR (400 MHz, CD3OD) δ ppm 9.56 (bs, 1H), 8.93 (s, 2H), 8.37 (d, J=4.77 Hz, 1H), 7.25 (s, 1H), 4.63 (dd, J=10.67, 3.14 Hz, 1H), 4.47 (dd, J=10.79, 6.02 Hz, 1H), 3.81-3.89 (m, 4H), 1.83-1.91 (m, 2H), 1.72 (t, J=6.53 Hz, 1H), 1.08 (d, J=5.02 Hz, 6H).

Workup

  1. customThe MeOH was removed
  2. dissolutionthe crude product was dissolved in EtOAc (20 mL)
  3. washThe ethyl acetate layer was washed with water (2×10 mL)
  4. dry with materialdried over sodium sulfate
  5. customRemoval of the solvent
  6. customgave crude product which
  7. customwas purified by silica-gel column (MeOH—CHCl3 mixture)

Sources & evidence

ORD record
ord-20a6e2699c0e47da93dbd8e497dd2509
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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