Hydrochloric Acid → HCID 73213797, compound

HRID 1398332Notes

Reaction equation

HRID 1398332 reaction equation
[F:1][C:2]([F:33])([F:32])[CH2:3][CH2:4][CH:5]([NH:24]C(=O)OC(C)(C)C)[CH2:6][O:7][C:8]1[CH:9]=[CH:10][C:11]2[C:20]3[C:15](=[CH:16][N:17]=[CH:18][CH:19]=3)[C:14](=[O:21])[N:13]([CH3:22])[C:12]=2[CH:23]=1.Cl.O1CCOCC1>C(OCC)C>[NH2:24][CH:5]([CH2:4][CH2:3][C:2]([F:32])([F:33])[F:1])[CH2:6][O:7][C:8]1[CH:9]=[CH:10][C:11]2[C:20]3[C:15](=[CH:16][N:17]=[CH:18][CH:19]=3)[C:14](=[O:21])[N:13]([CH3:22])[C:12]=2[CH:23]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86710333HCID 86710333, compound

Product 1

HCID 73213797HCID 73213797, compoundYield 86.3%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of tert-butyl (5,5,5-trifluoro-1-((6-methyl-5-oxo-5,6-dihydrobenzo[c][2,7]naphthyridin-8-yl)oxy)pentan-2-yl)carbamate (150 mg, 0.322 mmol) in diethyl ether (10 mL) under nitrogen atmosphere, cooled to 0° C. was added 4M HCl in 1,4-dioxane (0.098 mL, 0.392 mmol) slowly over a period of 5 min. The light yellow reaction mixture was stirred at 0° C. for 5 min then warmed to room temperature and allowed to stir for 12 h. The solvent was removed under reduced pressure. The residual yellow oil was diluted with water (3 mL) and extracted with EtOAc (2×4 mL). The aqueous layer was separated and treated with sat. Na2CO3 solution (3 mL). The resultant aqueous layer was extracted with EtOAc (3×5 mL). The combined organic layer s were separated and washed with water (2×5 mL), brine (1×5 mL) and dried over sodium sulfate. The filtrate was evaporated under reduced pressure and purified by SFC (CO2 and 0.5% DEA in Methanol) to afford 8-((2-amino-5,5,5-trifluoropentyl)oxy)-6-methylbenzo[c][2,7]naphthyridin-5(6H)-one (102.8 mg, 0.278 mmol, 86% yield) as a white solid. LC/MS (ESI) m/e 366.2 [(M+H)+, calcd for C18H19F3N3O2366.13]; LC/MS retention time (method C): tR=1.77 min; HPLC retention time (method A): tR=7.79 min; HPLC retention time (method B): tR=8.20 min. 1H NMR (400 MHz, MeOD) δ 9.48 (d, J=0.80 Hz, 1H), 8.78 (d, J=5.60 Hz, 1H), 8.44 (d, J=8.80 Hz, 1H), 8.27 (d, J=5.60 Hz, 1H), 7.17 (d, J=2.40 Hz, 1H), 7.12 (dd, J=2.40, 8.80 Hz, 1H), 4.17-4.20 (m, 1H), 4.09 (dd, J=6.00, 9.40 Hz, 1H), 3.82 (s, 3H), 3.28-3.28 (m, 1H), 2.33-2.49 (m, 2H), 1.92-1.99 (m, 1H), 1.73-1.80 (m, 1H).

Workup

  1. temperaturethen warmed to room temperature
  2. stirringto stir for 12 h
  3. customThe solvent was removed under reduced pressure
  4. additionThe residual yellow oil was diluted with water (3 mL)
  5. extractionextracted with EtOAc (2×4 mL)
  6. customThe aqueous layer was separated
  7. additiontreated with sat. Na2CO3 solution (3 mL)
  8. extractionThe resultant aqueous layer was extracted with EtOAc (3×5 mL)
  9. customThe combined organic layer s were separated
  10. washwashed with water (2×5 mL), brine (1×5 mL)
  11. dry with materialdried over sodium sulfate
  12. customThe filtrate was evaporated under reduced pressure
  13. custompurified by SFC (CO2 and 0.5% DEA in Methanol)

Sources & evidence

ORD record
ord-d01285d6ab914796ae9e2a265ef9ea08
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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