Hydrochloric Acid → HCID 73213874, compound

HRID 1398360Notes

Reaction equation

HRID 1398360 reaction equation
[CH:1]1([CH2:5][C@H:6]([NH:26]C(=O)OC(C)(C)C)[CH2:7][O:8][C:9]2[CH:10]=[CH:11][C:12]3[C:21]4[C:16](=[C:17]([CH3:22])[N:18]=[CH:19][CH:20]=4)[C:15](=[O:23])[N:14]([CH3:24])[C:13]=3[CH:25]=2)[CH2:4][CH2:3][CH2:2]1.Cl>C(OCC)C>[NH2:26][C@@H:6]([CH2:5][CH:1]1[CH2:2][CH2:3][CH2:4]1)[CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]2[C:21]3[C:16](=[C:17]([CH3:22])[N:18]=[CH:19][CH:20]=3)[C:15](=[O:23])[N:14]([CH3:24])[C:13]=2[CH:25]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86710354HCID 86710354, compound

Product 1

HCID 73213874HCID 73213874, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

An ambient temperature suspension of (S)-tert-butyl (1-cyclobutyl-3-((4,6-dimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)propan-2-yl)carbamate (70 mg, 0.155 mmol) in diethyl ether (1 mL) was treated with HCl (4M in 1,4-dioxane) (0.775 mL, 3.10 mmol) and stirred for 1 h. The resulting mixture was concentrated under reduced pressure to a yellow solid. The crude material was purified by reverse phase high performance liquid chromatography (Phenomenex Luna C18 30×100 mm 10 micron; water/methanol/TFA gradient elution). Fractions containing product were concentrated under reduced pressure. The resulting residue was partitioned between saturated aqueous sodium bicarbonate and ethyl acetate. The layers were separated and the aqueous was extracted twice more with ethyl acetate. The pooled organics were washed once with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure to afford (S)-8-(2-amino-3-cyclobutylpropoxy)-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (17 mg, 0.046 mmol, 30% yield) as a white solid. LC/MS, (ESI) m/z 352.3 [(M+H)+, calcd for C21H26N3O2 352.2]; HPLC retention time (method C): tR=14.15 min; HPLC retention time (method D): tR=14.78 min; 1H NMR (400 MHz, CHLOROFORM-d) δ 8.64 (d, J=5.8 Hz, 1H), 8.15 (d, J=9.0 Hz, 1H), 7.82 (d, J=5.8 Hz, 1H), 6.89 (dd, J=8.9, 2.4 Hz, 1H), 6.84 (d, J=2.3 Hz, 1H), 4.04 (dd, J=8.9, 3.9 Hz, 1H), 3.86 (dd, J=8.8, 7.5 Hz, 1H), 3.73 (s, 3H), 3.23 (tdd, J=7.5, 5.5, 3.8 Hz, 1H), 3.16 (s, 3H), 2.60-2.43 (m, 1H), 2.21-2.08 (m, 2H), 2.01-1.81 (m, 2H), 1.80-1.55 (m, 4H).

Workup

  1. concentrationThe resulting mixture was concentrated under reduced pressure to a yellow solid
  2. customThe crude material was purified by reverse phase high performance liquid chromatography (Phenomenex Luna C18 30×100 mm 10 micron; water/methanol/TFA gradient elution)
  3. additionFractions containing product
  4. concentrationwere concentrated under reduced pressure
  5. customThe resulting residue was partitioned between saturated aqueous sodium bicarbonate and ethyl acetate
  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 under reduced pressure

Sources & evidence

ORD record
ord-1be31980df1948a4980bbb4afabaf059
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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