Dimethylformamide → Methyl [7-cyano-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl][(1,1-dimethylethyl)oxy]acetate

HRID 572504ノート

反応式

HRID 572504 の反応式
Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([C:24]3[CH:29]=[CH:28][C:27]([CH3:30])=[C:26]([CH3:31])[CH:25]=3)=[C:7]([CH:14]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[C:15]([O:17][CH3:18])=[O:16])[N:8]([CH3:13])[C:9]2=[O:12])=[CH:4][CH:3]=1.[CH3:32][N:33](C)C=O>O.[C-]#N.[C-]#N.[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:32]([C:2]1[CH:11]=[C:10]2[C:5]([C:6]([C:24]3[CH:29]=[CH:28][C:27]([CH3:30])=[C:26]([CH3:31])[CH:25]=3)=[C:7]([CH:14]([O:19][C:20]([CH3:23])([CH3:21])[CH3:22])[C:15]([O:17][CH3:18])=[O:16])[N:8]([CH3:13])[C:9]2=[O:12])=[CH:4][CH:3]=1)#[N:33]

参加物

6

反応物 2

HCID 6228DimethylformamideHCID 68295047Methyl [7-bromo-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl][(1,1-dimethylethyl)oxy]acetate

生成物 1

HCID 68352905Methyl [7-cyano-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl][(1,1-dimethylethyl)oxy]acetate収率 82%

試薬・触媒・溶媒 3

HCID 11186Zinc cyanide (Zn(CN)2)触媒HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒

実験手順

A mixture of methyl [7-bromo-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl][(1,1-dimethylethyl)oxy]acetate (160 mg, 0.329 mmol) and Zn(CN)2 (38.6 mg, 0.329 mmol) in N,N-Dimethylformamide (DMF) (3289 μl) was degassed with N2 for 5 min, treated with Pd(Ph3P)4 (38.0 mg, 0.033 mmol), and irradiated in microwave at 120° C. for 30 min. The mixture was diluted with water, extracted with EtOAc, washed with water, brine, dried with Na2SO4, filtered, and concentrated. the residue was purified by column chromatography (SiO2, 0-60% EtOAc/Hexane) to afford methyl [7-cyano-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl][(1,1-dimethylethyl)oxy]acetate (116.8 mg, 0.270 mmol, 82% yield) as colorless oil that slowly became a white solid: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.85-8.76 (m, 1 H), 7.65 (ddd, J=1.9, 6.1, 8.3 Hz, 1 H), 7.30-7.24 (m, 1 H), 7.23-7.09 (m, 2 H), 7.07-6.96 (m, 1 H), 5.22 (s, 1 H), 3.80 (s, 1.5 H), 3.78 (s, 1.5 H), 3.70 (s, 1.5 H), 3.69 (s, 1.5 ; H), 2.37 (s, 3 H), 2.32 (s, 3 H), 1.02 (s, 4.5 H), 1.01 (s, 4.5 H); LCMS (m/z) ES+=433 (M+1).

後処理

  1. customwas degassed with N2 for 5 min
  2. customirradiated in microwave at 120° C. for 30 min
  3. extractionextracted with EtOAc
  4. washwashed with water, brine
  5. dry with materialdried with Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customthe residue was purified by column chromatography (SiO2, 0-60% EtOAc/Hexane)

出典と根拠

ORDレコード
ord-a41a4f92fa9c4e4aac6529cdccfab749
出典データセット
uspto-grants-2015_05
特許番号
US09029391B2

反応ノート

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