Trimethylsilylacetylene → 3-ethynyl-4-methyl-N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide

HRID 502699Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 502699
I[C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][C:28]=1[CH3:29])[C:5]([NH:7][C:8]1[CH:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:11]=[C:10]([CH2:18][N:19]2[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]2)[CH:9]=1)=[O:6].C[Si]([C:34]#[CH:35])(C)C>CC#N.CCN(CC)CC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[C:28]([C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][C:34]=1[CH3:35])[C:5]([NH:7][C:8]1[CH:13]=[C:12]([C:14]([F:15])([F:16])[F:17])[CH:11]=[C:10]([CH2:18][N:19]2[CH2:20][CH2:21][N:22]([CH3:25])[CH2:23][CH2:24]2)[CH:9]=1)=[O:6])#[CH:29]

Komponenten

7

Edukt 2

HCID 66111TrimethylsilylacetyleneHCID 594279993-iodo-4-methyl-N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide

Produkt 1

HCID 866079783-ethynyl-4-methyl-N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418476HCID 178418476, VerbindungKatalysatorHCID 6342AcetonitrileLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

To a mixture of 3-iodo-4-methyl-N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide (951 mg, 1.84 mmol), PdCl2(PPh3)2 (65 mg, 0.092 mmol) in MeCN (75 mL) and Et3N (20 mL) at room temperature was added trimethylsilylacetylene (0.8 mL, 5.52 mmol) followed by CuI (18 mg, 0.092 mmol). The resulting mixture was allowed to stir at room temperature for 2 h at which time the reaction mixture was concentrated under reduced pressure followed by reconstitution in MeOH (100 mL). To this mixture was added enough K2CO3 to saturate the mixture and the mixture was allowed to stir for about 1.5 h. The mixture was filtered through a pad of Celite. To the filtrate was added silica gel (˜20 mL) and the mixture was concentrated under reduced pressure, and purified via automated flash chromatography (silica gel, 0% to 15% MeOH in CH2Cl2, gradient elution) to afford 3-ethynyl-4-methyl-N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide.

Aufarbeitung

  1. concentrationwas concentrated under reduced pressure
  2. additionTo this mixture was added enough K2CO3
  3. concentrationto saturate the mixture
  4. stirringto stir for about 1.5 h
  5. filtrationThe mixture was filtered through a pad of Celite
  6. additionTo the filtrate was added silica gel (˜20 mL)
  7. concentrationthe mixture was concentrated under reduced pressure
  8. custompurified
  9. washflash chromatography (silica gel, 0% to 15% MeOH in CH2Cl2, gradient elution)

Quellen und Nachweise

ORD-Eintrag
ord-da39337c22db42189925be05e22dc5c3
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07776869B2

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