Hydrochloric Acid → HCID 72737640, compound

HRID 1398328Notes

Reaction equation

HRID 1398328 reaction equation
[F:1][C:2]1[C:17]([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][C:5]2[N:6]([CH3:15])[C:7](=[O:14])[C:8]3[C:13]([C:4]=2[CH:3]=1)=[CH:12][CH:11]=[N:10][CH:9]=3.Cl>C(OCC)C>[NH2:25][C@@H:20]([CH2:21][CH:22]([CH3:24])[CH3:23])[CH2:19][O:18][C:17]1[C:2]([F:1])=[CH:3][C:4]2[C:13]3[C:8](=[CH:9][N:10]=[CH:11][CH:12]=3)[C:7](=[O:14])[N:6]([CH3:15])[C:5]=2[CH:16]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86710331HCID 86710331, compound

Product 1

HCID 72737640HCID 72737640, compoundYield 73.2%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a stirred solution of (S)-tert-butyl (1-((9-fluoro-6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (25 mg, 0.056 mmol) in diethyl ether (4 mL) was added a 2M solution of hydrochloric acid in diethyl ether (42.5 μl, 0.085 mmol) at 0° C. dropwise over 10 min. The ice bath was removed and the reaction mixture was stirred at room temperature for 2 h. The solvent was removed and the crude material was taken up in water (5 mL). The aqueous layer was washed with ethyl acetate (3 mL) and treated with 10% NaHCO3 (20 mL). The resultant solution was extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with water (2×10 mL), dried (sodium sulfate), filtered and concentrated under reduced pressure to afford crude material which was purified via preparative TLC (40% Ethyl acetate in Hexane) to afford (S)-8-((2-amino-4-methylpentyl)oxy)-9-fluoro-6-methylbenzo[c][2,7]naphthyridin-5(6H)-one (15 mg, 0.041 mmol, 73% yield) as a white solid. LC/MS (ESI) m/e 344.2 [(M+H)+, calcd for C19H23FN3O2 344.2]; LC/MS retention time (method A): tR=1.35 min; HPLC retention time (method A): tR=8.31 min; HPLC retention time (method B): tR=8.85 min; 1H NMR (400 MHz, CD3OD) δ ppm 9.66-9.71 (m, 1H), 8.83-8.87 (m, 1H), 7.90-7.95 (m, 1H), 7.79-7.83 (m, 1H), 6.91-6.95 (m, 1H), 4.10-4.14 (m, 1H), 3.89-3.95 (m, 1H), 3.76-3.80 (m, 3H), 3.35-3.44 (m, 1H), 1.78-1.86 (m, 1H), 1.39 (t, J=7.00 Hz, 2H), 0.96-1.03 (m, 6H).

Workup

  1. customThe ice bath was removed
  2. customThe solvent was removed
  3. washThe aqueous layer was washed with ethyl acetate (3 mL)
  4. additiontreated with 10% NaHCO3 (20 mL)
  5. extractionThe resultant solution was extracted with ethyl acetate (3×10 mL)
  6. washThe combined organic layers were washed with water (2×10 mL)
  7. dry with materialdried (sodium sulfate)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto afford crude material which
  11. customwas purified via preparative TLC (40% Ethyl acetate in Hexane)

Sources & evidence

ORD record
ord-c643aab5ad784f32aa8e496cfc756960
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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