Cesium carbonate → N-(1-chloro-9-fluorobenzo[c]-1,6-naphthyridin-6-yl)piperidine-1-sulfonamide

HRID 2192991Notes

Reaction equation

HRID 2192991 reaction equation
[Cl:1][C:2]1[N:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:5]=1[C:6](Cl)=[N:7]2.C(=O)([O-])[O-].[Cs+].[Cs+].[N:24]1([S:30]([NH2:33])(=[O:32])=[O:31])[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.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].CO.C(Cl)Cl>[Cl:1][C:2]1[N:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:5]=1[C:6]([NH:33][S:30]([N:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1)(=[O:32])=[O:31])=[N:7]2

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 2767411-PiperidinesulfonamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)2×HCID 59375375HCID 59375375, compound

Product 1

HCID 86642860N-(1-chloro-9-fluorobenzo[c]-1,6-naphthyridin-6-yl)piperidine-1-sulfonamide

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 1,6-dichloro-9-fluorobenzo[c]-1,6-naphthyridine (30 mg, 0.11 mmol) in dioxane (3 mL) were added cesium carbonate (128 mg, 0.39 mmol), piperidine-1-sulfonamide (18.4 mg, 0.11 mmol), Xantphos, (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine), (10 mg, 0.02 mmol), and Pd2(dba)3 (5.14 mg, 5.62 μmol). The solution was degassed by bubbling N2 for 5 min and heated 80° C. overnight and worked up with EtOAc and H2O. The organic layers were dried with MgSO4, filtered, and concentrated by rotary evaporation to afford an oily residue. Silica gel column chromatography 100% CH2Cl2 to 25% MeOH afforded N-(1-chloro-9-fluorobenzo[c]-1,6-naphthyridin-6-yl)piperidine-1-sulfonamide. This intermediate was taken up in 6 N HCl (2 mL) and THF (2 mL) and heated to 85° C. for 2 hr. The reaction mixture was concentrated and purified by reverse phase HPLC 100% H2O to 100% MeCN to afford N-(9-fluoro-1-oxo-1,2-dihydrobenzo[c]-1,6-naphthyridin-6-yl)piperidine-1-sulfonamide. LRMS (ESI) calc'd for (C17H18FN4O3S) [M+H]+, 377.1; found 377.1.

Workup

  1. customThe solution was degassed
  2. customby bubbling N2 for 5 min
  3. dry with materialThe organic layers were dried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated by rotary evaporation
  6. customto afford an oily residue

Sources & evidence

ORD record
ord-eeff3acb97d7405ea812674a587dc6fd
Source dataset
uspto-grants-2012_12
Patent number
US08329722B2

Reaction notes

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