Ammonium Chloride → 6-(N-(3-Chloro-4-(1-hydroxyallyl)phenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide

HRID 1424883Notes

Reaction equation

HRID 1424883 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:10]([C:15]2[C:34]([CH:35]3[CH2:37][CH2:36]3)=[CH:33][C:18]3[C:19]([C:29]([NH:31][CH3:32])=[O:30])=[C:20]([C:22]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=4)[O:21][C:17]=3[CH:16]=2)[S:11]([CH3:14])(=[O:13])=[O:12])[CH:5]=[CH:6][C:7]=1[CH:8]=[O:9].[CH:38]([Mg]Br)=[CH2:39].[Cl-].[NH4+]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([N:10]([C:15]2[C:34]([CH:35]3[CH2:37][CH2:36]3)=[CH:33][C:18]3[C:19]([C:29]([NH:31][CH3:32])=[O:30])=[C:20]([C:22]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=4)[O:21][C:17]=3[CH:16]=2)[S:11]([CH3:14])(=[O:13])=[O:12])[CH:5]=[CH:6][C:7]=1[CH:8]([OH:9])[CH:38]=[CH2:39]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 1317323276-(N-(3-Chloro-4-formylphenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamideHCID 178418507HCID 178418507, compound2×

Product 1

HCID 1317323286-(N-(3-Chloro-4-(1-hydroxyallyl)phenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamideYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 6-(N-(3-chloro-4-formylphenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (1.17 g, 2.16 mmol) in THF (20 mL) was cooled to 0° and treated with vinylmagnesium bromide (1 M in THF, 4.76 mL). The reaction mixture was allowed to warm to rt as the bath melted. An additional portion of vinylmagnesium bromide (0.43 mL,) was added after a few h. Stirring was continued and the reaction mixture was poured into saturated ammonium chloride and extracted with EtOAc (2×). The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure. Purification by flash chromatography (silica gel, gradient of 0 to 60% EtOAc in hexanes) afforded the title compound (0.87 g, 71%) as a white foam. Enantiomers were separated by supercritical fluid chromatography (Chiral Tech ADH, 30% methanol, 140 bar, 40° C., 90 mL/min). Both enantiomers were white foams. The earlier eluting enantiomer 1 weighed 380 mg and the later eluting enantiomer 2 weighed 370 mg. Enantiomer #1 1H NMR (400 MHz, DMSO-d6) δ ppm 8.44 (q, 1H), 8.11 (s, 1H), 7.93-8.01 (m, 2H), 7.35-7.55 (m, 5H), 7.18 (s, 1H), 5.90 (ddd, 1H), 5.70 (d, 1H), 5.35 (t, 1H), 5.22 (dt, 1H), 5.08 (dt, 1H), 3.40 (s, 3H), 2.83 (d, 3H), 2.10-2.20 (m, 1H), 0.77-1.06 (m, 3H), 0.40-0.53 (m, 1H). LCMS (m/z, ES+)=569 (M+H+). Enantiomer #2 1H NMR (400 MHz, DMSO-d6) δ ppm 8.44 (q, 1H), 8.11 (s, 1H), 7.93-8.01 (m, 2H), 7.36-7.56 (m, 5H), 7.18 (s, 1H), 5.90 (ddd, 1H), 5.70 (d, 1H), 5.35 (t, 1H), 5.22 (dt, 1H), 5.08 (dt, 1H), 3.40 (s, 3H), 2.83 (d, 3H), 2.09-2.20 (m, 1H), 0.76-1.06 (m, 3H), 0.40-0.54 (m, 1H). LCMS (m/z, ES+)=569 (M+H+).

Workup

  1. extractionextracted with EtOAc (2×)
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customPurification by flash chromatography (silica gel, gradient of 0 to 60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-450441960c4a4695a6db73a46ca5fc79
Source dataset
uspto-grants-2015_01
Patent number
US08927593B2

Reaction notes

Loading…