Hydrochloric Acid → HCID 73213949, compound

HRID 1398367Notes

Reaction equation

HRID 1398367 reaction equation
[F:1][CH:2]([F:35])[C:3]1[C:19]([O:20][CH2:21][C@@H:22]([NH:27]C(=O)OC(C)(C)C)[CH2:23][CH:24]([CH3:26])[CH3:25])=[CH:18][C:6]2[N:7]([CH3:17])[C:8](=[O:16])[C:9]3[C:14]([C:5]=2[CH:4]=1)=[CH:13][CH:12]=[N:11][C:10]=3[CH3:15].Cl.O1CCOCC1>CO>[NH2:27][C@@H:22]([CH2:23][CH:24]([CH3:26])[CH3:25])[CH2:21][O:20][C:19]1[C:3]([CH:2]([F:1])[F:35])=[CH:4][C:5]2[C:14]3[C:9](=[C:10]([CH3:15])[N:11]=[CH:12][CH:13]=3)[C:8](=[O:16])[N:7]([CH3:17])[C:6]=2[CH:18]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86710360HCID 86710360, compound

Product 1

HCID 73213949HCID 73213949, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (S)-tert-butyl (1-((9-(difluoromethyl)-4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (500 mg, 0.480 mmol) in MeOH (10 mL) at 0° C. was added 4N HCl in 1,4-dioxane (20 mL, 80 mmol). The solution was warmed to room temperature and stirred for 2 h. The mixture was then was concentrated under reduced pressure. The residue was taken up in EtOAc and the EtOAc layer was washed with saturated aqueous NaHCO3 then H2O, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by prep. HPLC to afford (S)-8-((2-amino-4-methylpentyl)oxy)-9-(difluoromethyl)-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (60 mg, 0.149 mmol, 31% yield) as pale yellow solid. LC/MS (ESI) m/e 390.2 [(M+H)+, calcd for C21H26F2N3O2, 390.2]; LC/MS retention time (method A): tR=2.09 min; HPLC retention time (method A): tR=10.1 min; HPLC retention time (method B): tR=9.18 min; 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.73 (s, 1H), 8.66 (s, 2H), 7.07-7.41 (m, 2H), 4.66-4.53 (m, 1H), 4.52-4.49 (m, 1H), 3.78-3.89 (m, 4H), 3.22 (s, 3H), 1.74-1.88 (m, 2H), 1.63-1.71 (m, 1H), 1.04 (m, 6H).

Workup

  1. concentrationThe mixture was then was concentrated under reduced pressure
  2. washthe EtOAc layer was washed with saturated aqueous NaHCO3
  3. dry with materialH2O, dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by prep

Sources & evidence

ORD record
ord-3b4d36a954dc42debe58b8d0658f43ca
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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