Potassium Hydroxide → HCID 59375672, compound

HRID 2193025Notes

Reaction equation

HRID 2193025 reaction equation
Cl[C:2]1[N:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:5]=1[C:6]([O:12][CH:13]([CH3:15])[CH3:14])=[N:7]2.[OH-].[K+].C(P(C(C)(C)C)C1C=CC=CC=1C1C(CCC)=CC(CCC)=CC=1CCC)(C)(C)C.[O:53]1CCOCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[F:20][C:18]1[CH:17]=[CH:16][C:5]2[C:6]([O:12][CH:13]([CH3:15])[CH3:14])=[N:7][C:8]3[CH:9]=[CH:10][NH:11][C:2](=[O:53])[C:3]=3[C:4]=2[CH:19]=1

Participants

7

Reactant 4

HCID 14797Potassium HydroxideHCID 312751,4-DioxaneHCID 59375524HCID 59375524, compoundHCID 67346612HCID 67346612, compound

Product 1

HCID 59375672HCID 59375672, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

1-chloro-9-fluoro-6-isopropoxybenzo[c]-1,6-naphthyridine (107 mg, 0.368 mmol), potassium hydroxide (83.0 mg, 1.47 mmol), 2-di-t-butylphosphino-2′,4′,6′-tri-1-propyl-1,1′-biphenyl (31.3 mg, 0.0740 mmol), and Pd2(dba)3 (33.7 mg, 0.0370 mmol) were combined in a vial. 1,4-Dioxane (2.2 mL) and water (1.5 mL), were added, and the resulting suspension was degassed with argon for 10 min. The reaction mixture was heated to 100° C. and stirred for 16 h. After cooling to room temperature, the reaction mixture was added to saturated aqueous ammonium chloride (40 mL). The aqueous layer was extracted with ethyl acetate (2×40 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated to a crude residue. The crude material was purified by preparative reverse phase HPLC eluting with an acetonitrile/water (with 0.05% TFA as a modifier) gradient, to afford 9-fluoro-6-isopropoxybenzo[c]-1,6-naphthyridin-1(2H)-one. 1H NMR (500 MHz, DMSO-D6) δ 11.74 (s, 1H), 9.55 (d, 1H), 8.33 (dd, 1H), 7.53 (overlapping m, 2H), 6.56 (d, 1H), 5.64 (septet, 1H), 1.43 (d, 6H). LRMS (ESI) calc'd for (C15H13FN2O2) [M+H]+, 273.1; found 273.0.

Workup

  1. customthe resulting suspension was degassed with argon for 10 min
  2. temperatureAfter cooling to room temperature
  3. additionthe reaction mixture was added to saturated aqueous ammonium chloride (40 mL)
  4. extractionThe aqueous layer was extracted with ethyl acetate (2×40 mL)
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to a crude residue
  8. customThe crude material was purified by preparative reverse phase HPLC
  9. washeluting with an acetonitrile/water (with 0.05% TFA as a modifier) gradient

Sources & evidence

ORD record
ord-7778c384ba7c439f9ee803f4dd69d7ac
Source dataset
uspto-grants-2012_12
Patent number
US08329722B2

Reaction notes

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