Hydrochloric Acid → HCID 73213801, compound

HRID 1398357Notes

Reaction equation

HRID 1398357 reaction equation
[CH3:1][C:2]1[N:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[N:9]([CH3:13])[C:8]1[CH:14]=[C:15]([O:18][CH2:19][C@H:20]([NH:25]C(=O)OC(C)(C)C)[CH2:21][CH:22]([CH3:24])[CH3:23])[CH:16]=[CH:17][C:7]2=1.Cl>ClCCl>[NH2:25][C@H:20]([CH2:21][CH:22]([CH3:24])[CH3:23])[CH2:19][O:18][C:15]1[CH:16]=[CH:17][C:7]2[C:6]3[C:11](=[C:2]([CH3:1])[N:3]=[CH:4][CH:5]=3)[C:10](=[O:12])[N:9]([CH3:13])[C:8]=2[CH:14]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86710351HCID 86710351, compound

Product 1

HCID 73213801HCID 73213801, compoundYield 14.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

An ambient temperature solution of (R)-tert-butyl (1-((4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (102 mg, 0.232 mmol) in dichloromethane (1 mL) was treated with HCl (1.160 mL, 4.64 mmol) and stirred for 1 h. The resulting mixture was concentrated to an oil and purified by reverse phase high performance liquid chromatography (Phenomenex Luna C18 30×100 mm 10 micron; water/methanol/0.1% TFA gradient elution). Fractions containing product were neutralized with saturated aqueous sodium bicarbonate and concentrated under reduced pressure. The residue was partitioned between ethyl acetate and brine and the layers were separated. The aqueous was extracted twice more with ethyl acetate and the pooled organics were washed once with brine, dried over magnesium sulfate, filtered, and concentrated to afford (R)-8-((2-amino-4-methylpentyl)oxy)-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (11.5 mg, 0.033 mmol, 14% yield) as a milky oil. LC/MS, (ESI) m/z 340.2 [(M+H)+, calcd for C20H26N3O2 340.2]; HPLC retention time (method C): tR=13.02 min; HPLC retention time (method D): tR=13.05 min; 1H NMR (500 MHz, METHANOL-d4) δ 8.68-8.63 (m, 2H), 8.58 (d, J=9.0 Hz, 1H), 7.22 (dd, J=9.0, 2.3 Hz, 1H), 7.20 (d, J=2.3 Hz, 1H), 4.52 (dd, J=10.5, 3.3 Hz, 1H), 4.34 (dd, J=10.7, 6.6 Hz, 1H), 3.82 (s, 3H), 3.80-3.75 (m, 1H), 3.25 (s, 3H), 1.91-1.81 (m, 1H), 1.80-1.73 (m, 1H), 1.72-1.64 (m, 1H), 1.07 (d, J=5.8 Hz, 3H), 1.06 (d, J=5.8 Hz, 3H).

Workup

  1. concentrationThe resulting mixture was concentrated to an oil
  2. custompurified by reverse phase high performance liquid chromatography (Phenomenex Luna C18 30×100 mm 10 micron; water/methanol/0.1% TFA gradient elution)
  3. additionFractions containing product
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was partitioned between ethyl acetate and brine
  6. customthe layers were separated
  7. extractionThe aqueous was extracted twice more with ethyl acetate
  8. washthe pooled organics were washed once with brine
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-600efb87698244b59adc7d986a9d994e
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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