Water → N-[2-cyclopropyl-7-(1,5-dimethyl-6-oxopyridin-3-yl)-1-benzofuran-5-yl]ethanesulfonamide

HRID 518577Notes

Reaction equation

HRID 518577 reaction equation
[CH:1]1([C:4]2[O:5][C:6]3[C:12](I)=[CH:11][C:10]([NH:14][S:15]([CH2:18][CH3:19])(=[O:17])=[O:16])=[CH:9][C:7]=3[CH:8]=2)[CH2:3][CH2:2]1.[CH3:20][N:21]1[CH:26]=[C:25](B2OC(C)(C)C(C)(C)O2)[CH:24]=[C:23]([CH3:36])[C:22]1=[O:37].C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH:1]1([C:4]2[O:5][C:6]3[C:12]([C:25]4[CH:24]=[C:23]([CH3:36])[C:22](=[O:37])[N:21]([CH3:20])[CH:26]=4)=[CH:11][C:10]([NH:14][S:15]([CH2:18][CH3:19])(=[O:17])=[O:16])=[CH:9][C:7]=3[CH:8]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 962Water2×HCID 11430Potassium CarbonateHCID 712703091,3-Dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydropyridin-2-oneHCID 118022204N-(2-cyclopropyl-7-iodo-1-benzofuran-5-yl)ethanesulfonamide

Product 1

HCID 118021844N-[2-cyclopropyl-7-(1,5-dimethyl-6-oxopyridin-3-yl)-1-benzofuran-5-yl]ethanesulfonamideYield 47%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of the title compound from Step 3 (500 mg, 1.3 mmol) and 1,3-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-one (380 mg, 1.5 mmol) in 10 mL of DMF was added K2CO3 (50 mg, 3.8 mmol), water (2 mL) and Pd(dppf)Cl2 (30 mg) under N2. The reaction mixture was heated to 100° C. for 1 h. The resulting mixture was poured into 100 mL of water and extracted with DCM (100 mL×2). The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel eluting with EtOAc to give the title compound (230 mg, 47% yield) as a white solid. 1H NMR (CDCl3, 400 MHz): δ 7.81 (d, J=3.6 Hz, 1H), 7.67-7.66 (m, 1H), 7.26 (t, J=1.2 Hz, 1H), 7.12 (d, J=3.2 Hz, 1H), 6.54 (br, 1H), 6.36 (d, J=0.8 Hz, 1H), 3.67 (s, 3H), 3.14-3.06 (m, 2H), 2.25 (s, 3H), 2.11-2.00 (m, 1H), 1.38-1.43 (m, 3H), 1.09-0.92 (m, 4H). LCMS: 387 (M+1)+.

Workup

  1. extractionextracted with DCM (100 mL×2)
  2. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by column chromatography on silica gel eluting with EtOAc

Sources & evidence

ORD record
ord-cd0376b772cf481ab21eb1d7f180b670
Source dataset
uspto-grants-2015_08
Patent number
US09115114B2

Reaction notes

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