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 883533Notes

Reaction equation

HRID 883533 reaction equation
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@H:21]12[CH2:27][C@H:24]([NH:25][CH2:26]1)[CH2:23][N:22]2[C:28]([OH:30])=[O:29].[CH3:31][C:32]([CH3:35])([O-])[CH3:33].[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:32]([O:29][C:28]([N:22]1[CH2:23][C@@H:24]2[CH2:27][C@H:21]1[CH2:26][N:25]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:30])([CH3:35])([CH3:33])[CH3:31]

Participants

6

Reactant 3

HCID 114067748-Iodo-3-(phenylsulfonyl)quinolineHCID 20580781(1S,4S)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acidHCID 23676156Sodium t-butoxide

Product 1

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

Reagents, catalysts & solvents 2

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

Conditions

Temperature
40 °C

Procedure

3-sulfonyl-8-iodo quinoline (D6) (200 mg, 0.48 mMol), (1S,4S)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tent-butyl ester (95 mg, 0.48 mmol), sodium t butoxide (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;

Workup

  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

Sources & evidence

ORD record
ord-87bb5f529cd74ddaab64f0ac8cf300df
Source dataset
uspto-grants-2012_08
Patent number
US08236947B2

Reaction notes

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