Hydrochloric Acid → HCID 73213877, compound

HRID 1398362Notes

Reaction equation

HRID 1398362 reaction equation
[CH:1]1([CH2:4][C@H:5]([NH:26]C(=O)OC(C)(C)C)[CH2:6][O:7][C:8]2[C:9]([CH3:25])=[CH:10][C:11]3[C:20]4[C:15](=[C:16]([CH3:21])[N:17]=[CH:18][CH:19]=4)[C:14](=[O:22])[N:13]([CH3:23])[C:12]=3[CH:24]=2)[CH2:3][CH2:2]1.Cl>CO>[NH2:26][C@@H:5]([CH2:4][CH:1]1[CH2:3][CH2:2]1)[CH2:6][O:7][C:8]1[C:9]([CH3:25])=[CH:10][C:11]2[C:20]3[C:15](=[C:16]([CH3:21])[N:17]=[CH:18][CH:19]=3)[C:14](=[O:22])[N:13]([CH3:23])[C:12]=2[CH:24]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86710355HCID 86710355, compound

Product 1

HCID 73213877HCID 73213877, compoundYield 93%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

An ambient temperature solution of (S)-tert-butyl (1-cyclopropyl-3-((4,6,9-trimethyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)propan-2-yl)carbamate (41 mg, 0.091 mmol) in methanol (0.5 mL) was treated with HCl (4M in 1,4-dioxane) (0.454 mL, 1.816 mmol) and stirred for 1 h. The resulting mixture was concentrated under reduced pressure to 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). Product containing fractions were neutralized with saturated aqueous sodium bicarbonate and concentrated under reduced pressure. The resulting residue was partitioned between water and ethyl acetate and the layers were separated. The aqueous was extracted twice more with ethyl acetate and the pooled organics were dried over magnesium sulfate, filtered, and concentrated to afford (S)-8-(2-amino-3-cyclopropylpropoxy)-4,6,9-trimethylbenzo[c][2,7]naphthyridin-5(6H)-one (10.7 mg, 0.028 mmol, 93% yield) as a colorless solid. LC/MS, (ESI) m/z 352.2 [(M+H)+, calcd for C21H26N3O2 352.2]; HPLC retention time (method C): tR=13.71 min; HPLC retention time (method D): tR=14.29 min; 1H NMR (400 MHz, CHLOROFORM-d) δ 8.63 (d, J=5.5 Hz, 1H), 7.98 (s, 1H), 7.84 (d, J=5.8 Hz, 1H), 6.74 (s, 1H), 4.15 (dd, J=8.8, 4.0 Hz, 1H), 4.00 (dd, J=8.7, 6.9 Hz, 1H), 3.76 (s, 3H), 3.50-3.37 (m, 1H), 3.17 (s, 3H), 2.37 (s, 3H), 1.61-1.44 (m, 2H), 1.02-0.74 (m, 1H), 0.68-0.45 (m, 2H), 0.30-0.06 (m, 2H).

Workup

  1. concentrationThe resulting mixture was concentrated under reduced pressure to 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. additionProduct containing fractions
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was partitioned between water and ethyl acetate
  6. customthe layers were separated
  7. extractionThe aqueous was extracted twice more with ethyl acetate
  8. dry with materialthe pooled organics were dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-81847f2494df43aa8369b7c572dd60bb
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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