Hydrochloric Acid → 8-((2-amino-2,4-dimethylpentyl)oxy)-7-fluoro-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one

HRID 1398376Notes

Reaction equation

HRID 1398376 reaction equation
[F:1][C:2]1[C:7]2[N:8]([CH3:18])[C:9](=[O:17])[C:10]3[C:15]([C:6]=2[CH:5]=[CH:4][C:3]=1[O:19][CH2:20][C:21]([NH:27]C(=O)OC(C)(C)C)([CH3:26])[CH2:22][CH:23]([CH3:25])[CH3:24])=[CH:14][CH:13]=[N:12][C:11]=3[CH3:16].Cl.O1CCOCC1>CO>[NH2:27][C:21]([CH3:26])([CH2:22][CH:23]([CH3:24])[CH3:25])[CH2:20][O:19][C:3]1[CH:4]=[CH:5][C:6]2[C:15]3[C:10](=[C:11]([CH3:16])[N:12]=[CH:13][CH:14]=3)[C:9](=[O:17])[N:8]([CH3:18])[C:7]=2[C:2]=1[F:1]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86710367Tert-butyl (1-((7-fluoro-4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-2,4-dimethylpentan-2-yl)carbamate

Product 1

HCID 732139508-((2-amino-2,4-dimethylpentyl)oxy)-7-fluoro-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-oneYield 6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl (1-((7-fluoro-4,6-dimethyl-5-oxo-5,6 dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-2,4-dimethylpentan-2-yl)carbamate (200 mg, 0.424 mmol) in MeOH (6 mL) at 0° C. was added 4M HCl in 1,4-dioxane (3 mL, 99.0 mmol). The reaction mixture was stirred at 0° C. for 2 h. After 2 h, the reaction mixture was concentrated under reduced pressure to afford crude product which was purified by preparative HPLC to afford 8-((2-amino-2,4-dimethylpentyl)oxy)-7-fluoro-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (10 mg, 0.024 mmol, 6% yield) as an off-white solid. LC/MS (ESI) m/e 372.0 [(M+H)+, calcd for C21H27FN3O2 372.2]; LC/MS retention time (method G): tR=1.99 min. HPLC retention time (method A): tR=8.37 min; HPLC retention time (method B): tR=9.72 min. 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.58 (d, J=6 Hz, 1H), 8.22 (dd, J=9.2 Hz, J=2 Hz, 1H), 8.14 (d, J=6 Hz, 1H), 7.23 (m, 1H), 4.31 (d, J=10 Hz, 1H), 4.23 (d, J=10.4 Hz, 1H), 3.88 (d, J=9.2 Hz, 3H), 3.06 (s, 3H), 1.90 (m, 2H), 1.73 (m, 1H), 1.52 (s, 3H), 1.05 (m, 6H).

Workup

  1. waitAfter 2 h
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. customto afford crude product which
  4. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-bf17cc2bce814a16b69cd95a28912c8b
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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