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

HRID 2192991ノート

反応式

HRID 2192991 の反応式
[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

参加物

9

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-eeff3acb97d7405ea812674a587dc6fd
出典データセット
uspto-grants-2012_12
特許番号
US08329722B2

反応ノート

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