Tetrahydrofuran → HCID 24996234, compound

HRID 1673202Notes

Reaction equation

HRID 1673202 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[NH:14][C:13](=[O:15])[C:12]([C:16]#N)=[CH:11][C:10]=1[C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=1.C[Mg+].[Br-].[CH3:28][C:29]([CH3:33])=[CH:30][Mg]Br.C1C[O:37]CC1>>[Cl:24][C:21]1[CH:20]=[CH:19][C:18]([C:10]2[CH:11]=[C:12]3[C:16](=[O:37])[CH2:28][C:29]([CH3:33])([CH3:30])[O:15][C:13]3=[N:14][C:9]=2[C:3]2[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=2[Cl:1])=[CH:23][CH:22]=1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 219848256-(2,4-Dichlorophenyl)-5-(4-chlorophenyl)-2-oxo-1,2-dihydropyridine-3-carbonitrileHCID 178418689HCID 178418689, compoundHCID 178448304HCID 178448304, compound

Product 1

HCID 24996234HCID 24996234, compound

Conditions

Temperature
50 °C

Procedure

To the product of Step B (13.15 g, 35 mmol) in THF (160 mL) was added MeMgBr (1.4 M in toluene/THF, 26.25 mL, 36.75 mmol). After stirring 3 min, 2-methylprop-1-enylmagnesium bromide (0.5 M in THF, 100 mL, 50 mmol) was added and the temperature was increased to 50° C. After 20 min the reaction was cooled, quenched with 2 M HCl and diluted with EtOAc. The reaction was stirred for 3 days before work up. The solution was washed twice with brine, followed by twice with saturated aq NaHCO3. The concentrated residue was purified by flash chromatography on silica gel gradient eluted with 0-25% EtOAc in hexane to afford the title compound. (LC-2) HPLC/MS: 432.2 (M+1), 434.2 (M+3); Rt=4.15 mm.

Workup

  1. temperatureAfter 20 min the reaction was cooled
  2. customquenched with 2 M HCl
  3. additiondiluted with EtOAc
  4. stirringThe reaction was stirred for 3 days before work up
  5. washThe solution was washed twice with brine
  6. customThe concentrated residue was purified by flash chromatography on silica gel gradient
  7. washeluted with 0-25% EtOAc in hexane

Sources & evidence

ORD record
ord-93618027e0784caa90c78b2b88df80db
Source dataset
uspto-grants-2011_08
Patent number
US07999107B2

Reaction notes

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