Allyl Alcohol → 6-(N-(3-chloro-4-(3-hydroxyprop-1-en-2-yl)phenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide

HRID 1424871Notes

Reaction equation

HRID 1424871 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]([C:13]2[C:32]([CH:33]3[CH2:35][CH2:34]3)=[CH:31][C:16]3[C:17]([C:27]([NH:29][CH3:30])=[O:28])=[C:18]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[O:19][C:15]=3[CH:14]=2)[S:9]([CH3:12])(=[O:11])=[O:10])=[CH:4][C:3]=1[Cl:36].[CH2:37]([OH:40])[CH:38]=[CH2:39].C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C>CS(C)=O.F[B-](F)(F)F.C([N+]1C=CN(C)C=1)CCC.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:36][C:3]1[CH:4]=[C:5]([N:8]([C:13]2[C:32]([CH:33]3[CH2:35][CH2:34]3)=[CH:31][C:16]3[C:17]([C:27]([NH:29][CH3:30])=[O:28])=[C:18]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[O:19][C:15]=3[CH:14]=2)[S:9]([CH3:12])(=[O:11])=[O:10])[CH:6]=[CH:7][C:2]=1[C:38]([CH2:37][OH:40])=[CH2:39]

Participants

9

Reactant 4

HCID 7858Allyl AlcoholHCID 8471TriethylamineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 1317322566-(N-(4-Bromo-3-chlorophenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide

Product 1

HCID 1317323206-(N-(3-chloro-4-(3-hydroxyprop-1-en-2-yl)phenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamideYield 24%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolventHCID 27341781-Butyl-3-methylimidazolium tetrafluoroborateSolvent

Conditions

Temperature
135 °C

Procedure

A mixture of 6-(N-(4-bromo-3-chlorophenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (327 mg, 0.552 mmol), allyl alcohol (0.475 mL, 6.9 mmol), palladium(II) acetate (29 mg, 0.132 mmol), 1,3-bis(diphenylphosphino)propane (108 mg, 0.26 mmol) and triethylamine (0.7 mL, 4.9 mmol) in DMSO (2 mL) and 1-butyl-3-methylimidazolium tetrafluoroborate (2 mL) was heated at 135° C. in a sealed tube for 59 hours. The reaction mixture was diluted with ethyl acetate and filtered through Celite. The filtrate was washed with water and brine, dried over sodium sulfate and concentrated. Chromatography on silica gel (hexane:ethyl acetate) gave 75 mg (24%) of 6-(N-(3-chloro-4-(3-hydroxyprop-1-en-2-yl)phenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide. 1H NMR (400 MHz, chloroform-d) δ ppm 7.84-7.97 (m, 2H) 7.60 (s, 1H) 7.48 (s, 1H) 7.37-7.41 (m, 1H) 7.29-7.32 (m, 1H) 7.28 (s, 1H) 7.16-7.24 (m, 3H) 5.77-5.97 (m, 1H) 5.51-5.63 (m, 1H) 5.17 (s, 1H) 4.34-4.46 (m, 2H) 3.28 (s, 3H) 3.00 (d, J=4.88 Hz, 3H) 2.1 (m, 1H) 0.99-1.10 (m, 1H) 0.77-0.93 (m, 2H) 0.48-0.73 (m, 1H).). LCMS (m/z, ES+)=569 (M+H+).

Workup

  1. filtrationfiltered through Celite
  2. washThe filtrate was washed with water and brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-42cbb1eac03149609e43b607b9f7c922
Source dataset
uspto-grants-2015_01
Patent number
US08927593B2

Reaction notes

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