8-Iodo-3-(phenylsulfonyl)quinoline → (1S,4S)-5-(3-benzenesulfonyl-quinolin-8-yl)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

HRID 1714747

Reaktionsgleichung

Reaktionsgleichung von HRID 1714747
I[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][C:8]([S:12]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)(=[O:14])=[O:13])=[CH:7]2.[C:21]([O:25][C:26]([N:28]1[CH2:33][C@@H:32]2[CH2:34][C@H:29]1[CH2:30][NH:31]2)=[O:27])([CH3:24])([CH3:23])[CH3:22].CC(C)([O-])C.[Na+]>C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.[Pd].[Pd].C1(P[C-]2C=CC=C2)C=CC=CC=1.[C-]1(PC2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:21]([O:25][C:26]([N:28]1[CH2:33][C@@H:32]2[CH2:34][C@H:29]1[CH2:30][N:31]2[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][C:8]([S:12]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)(=[O:14])=[O:13])=[CH:7]2)=[O:27])([CH3:24])([CH3:22])[CH3:23]

Komponenten

6

Edukt 3

HCID 114067748-Iodo-3-(phenylsulfonyl)quinolineHCID 11521263(1S,4S)-2-Boc-2,5-diazabicyclo[2.2.1]heptaneHCID 23676156Sodium t-butoxide

Produkt 1

HCID 67313656(1S,4S)-5-(3-benzenesulfonyl-quinolin-8-yl)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl esterAusbeute 70 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11615059Di-palladium tetrakis-(dibenzylidene acetone)KatalysatorHCID 133083342Bis(cyclopenta-2,4-dien-1-yl(phenyl)phosphane);iron(2+)Katalysator

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

3-sulfonyl-8-iodo quinoline (D6) (200 mg, 0.48 mMol), (1S,4S)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (95 mg, 0.48 mmol), sodium tbutoxide (65 mg, 0.68 mmol), di-palladium tetrakis-(dibenzylidene acetone) (88 mg, 0.1 mmol) and 1,1′-diphenylphosphino ferrocene (161 mg, 0.3 mMol) were suspended in degassed dry dioxan (2 ml). The mixture was stirred under argon at 40° C. for 16 hours. The solvent was removed and the residue was purified by chromatography on silica using 30% ethyl acetate in hexane to afford (1S,4S)-5-(3-benzenesulfonyl-quinolin-8-yl)-2,5-diaza-bicyclo[2.2.1]heptane-2- carboxylic acid tert-butyl ester in 70% yield. This material (160 mg) was treated with 4M hydrochloric acid (1 ml) and dioxan (1 ml) with stirring at 80° C. for 30 mins. The solvent was removed to afford the title compound E43 as a yellow solid;

Aufarbeitung

  1. customin degassed dry dioxan (2 ml)
  2. customThe solvent was removed
  3. customthe residue was purified by chromatography on silica using 30% ethyl acetate in hexane

Quellen und Nachweise

ORD-Eintrag
ord-a9b24f3efb2049dc8a61a6da38d768a5
Quelldatensatz
uspto-grants-2010_09
Patentnummer
US07799774B2

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