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

HRID 2192991노트

반응식

HRID 2192991 반응식
[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

참가 물질

9

반응물 4

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

생성물 1

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

시약·촉매·용매 4

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 887Methanol용매HCID 6344Dichloromethane용매HCID 312751,4-Dioxane용매

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온도
80 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-eeff3acb97d7405ea812674a587dc6fd
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08329722B2

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