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

HRID 1042654노트

반응식

HRID 1042654 반응식
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]

참가 물질

7

반응물 2

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

생성물 1

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

시약·촉매·용매 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418476HCID 178418476, 화합물촉매HCID 6342Acetonitrile용매HCID 8471Triethylamine용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-d27b1910123c4dff97d9e2a786c2b690
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08557996B2

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