1-Methylpiperazine → 1-[(2E)-3-(4-{[3-Ethyl-6-(methyloxy)-2-phenyl-1-naphthalenyl]oxy}phenyl)-2-propenoyl]-4-methylpiperazine

HRID 1992857Notes

Reaction equation

HRID 1992857 reaction equation
[CH2:1]([C:3]1[C:4]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[C:5]([O:15][C:16]2[CH:21]=[CH:20][C:19](/[CH:22]=C/C(O)=O)=[CH:18][CH:17]=2)[C:6]2[C:11]([CH:12]=1)=[CH:10][C:9]([O:13][CH3:14])=[CH:8][CH:7]=2)[CH3:2].[C:33](Cl)(=[O:37])[C:34](Cl)=O.[CH3:39][N:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1>C(Cl)Cl>[CH2:1]([C:3]1[C:4]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)=[C:5]([O:15][C:16]2[CH:21]=[CH:20][C:19](/[CH:22]=[CH:34]/[C:33]([N:43]3[CH2:44][CH2:45][N:40]([CH3:39])[CH2:41][CH2:42]3)=[O:37])=[CH:18][CH:17]=2)[C:6]2[C:11]([CH:12]=1)=[CH:10][C:9]([O:13][CH3:14])=[CH:8][CH:7]=2)[CH3:2]

Participants

5

Reactant 3

HCID 531671-MethylpiperazineHCID 65578Oxalyl chlorideHCID 68537521(2E)-3-(4-{[3-Ethyl-6-(methyloxy)-2-phenyl-1-naphthalenyl]oxy}phenyl)-2-propenoic acid

Product 1

HCID 685367431-[(2E)-3-(4-{[3-Ethyl-6-(methyloxy)-2-phenyl-1-naphthalenyl]oxy}phenyl)-2-propenoyl]-4-methylpiperazineYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (2E)-3-(4-{[3-Ethyl-6-(methyloxy)-2-phenyl-1-naphthalenyl]oxy}phenyl)-2-propenoic acid (60) (0.10 g, 0.24 mmol) in CH2Cl2 (3 mL) at room temperature was added oxalyl chloride (63 μL, 0.71 mmol). The mixture was stirred at room temperature overnight. CH2Cl2 and excess of oxalyl chloride were removed under vacuum. The residue was dissolved in CH2Cl2 (4 mL), cooled in an ice bath, 1-methyl piperazine (40 μL, 0.35 mmol) was added. The resulting mixture was allowed to stir at room temperature overnight. Diluted with CH2Cl2 (50 mL), the mixture was washed with saturated aqueous NaHCO3, 0.5 N NaOH and brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give the crude product as a yellow oil. The crude product was purified by flash chromatography over SiO2 with CHCl3:MeOH (75:1 to 50:1) to give 84 mg (70%) of compound 62 as a white foam. 1H NMR (400 MHz, CH3OH-d4): δ 1.09 (t, J=7.5 Hz, 3H), 2.32 (s, 3H), 2.47 (br s, 4H), 2.58 (q, J=7.5 Hz, 2H), 3.71 (br s, 4H), 3.92 (s, 3H), 6.54 (d, J=8.7 Hz, 2H), 6.91 (d, J=15.4 Hz, 1H), 7.02 (dd, J1=9.2 Hz, J2=2.4 Hz, 1H), 7.10-7.16 (m, 2H), 7.18-7.28 (m, 3H), 7.30 (d, J=2.4 Hz, 1H), 7.37 (d, J=8.8 Hz, 2H), 7.44 (d, J=15.4 Hz, 1H), 7.63 (d, J=9.3 Hz, 1H), 7.66 (s, 1H). LCMS (APCI): m/z 507 (M+H)+.

Workup

  1. customCH2Cl2 and excess of oxalyl chloride were removed under vacuum
  2. dissolutionThe residue was dissolved in CH2Cl2 (4 mL)
  3. temperaturecooled in an ice bath
  4. stirringto stir at room temperature overnight
  5. washthe mixture was washed with saturated aqueous NaHCO3, 0.5 N NaOH and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated
  9. customto give the crude product as a yellow oil
  10. customThe crude product was purified by flash chromatography over SiO2 with CHCl3:MeOH (75:1 to 50:1)

Sources & evidence

ORD record
ord-9639439ea54b45e1b4ab408c8782d328
Source dataset
uspto-grants-2010_01
Patent number
US07649093B2

Reaction notes

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