三(邻甲基苯基)磷 → 4-(2,4-dimethylthiophen-3-yl)-3-(2-fluoro-4-methoxyphenyl)-1-methyl-1H-pyrazole-5-carbonitrile

HRID 1410171笔记

反应方程式

HRID 1410171 反应方程式
Br[C:2]1[C:3]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][C:11]=2[F:18])=[N:4][N:5]([CH3:9])[C:6]=1[C:7]#[N:8].C([Sn](CCCC)(CCCC)[C:24]1[C:28]([CH3:29])=[CH:27][S:26][C:25]=1[CH3:30])CCC.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CN(C=O)C>[CH3:30][C:25]1[S:26][CH:27]=[C:28]([CH3:29])[C:24]=1[C:2]1[C:3]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][C:11]=2[F:18])=[N:4][N:5]([CH3:9])[C:6]=1[C:7]#[N:8]

参与物

6

反应物 3

HCID 80271三(邻甲基苯基)磷HCID 67120033Tributyl(2,4-dimethylthiophen-3-yl)stannaneHCID 671200524-bromo-3-(2-fluoro-4-methoxyphenyl)-1-methyl-1H-pyrazole-5-carbonitrile

产物 1

HCID 671200444-(2,4-dimethylthiophen-3-yl)-3-(2-fluoro-4-methoxyphenyl)-1-methyl-1H-pyrazole-5-carbonitrile收率 32%

试剂、催化剂与溶剂 2

HCID 9811564三(二亚苄基丙酮)二钯催化剂HCID 6228N,N-二甲基甲酰胺溶剂

反应条件

温度
85 °C

实验过程

4-bromo-3-(2-fluoro-4-methoxyphenyl)-1-methyl-1H-pyrazole-5-carbonitrile (49 mg, 0.16 mmol), tributyl(2,4-dimethylthiophen-3-yl)stannane (82.24 mg, 0.20 mmol), Pd2(dba)3 (14.44 mg, 0.02 mmol) and trio-tolylphosphine (9.6 mg, 0.03 mmol) were mixed with 1.5 mL DMF and the mixture was degassed under nitrogen in a vial. The vial was sealed and the reaction was heated at 85° C. over night. Water was added, the mixture was extracted with CH2Cl2 and the organic layer was concentrated. The crude product was purified on silica to give 4-(2,4-dimethylthiophen-3-yl)-3-(2-fluoro-4-methoxyphenyl)-1-methyl-1H-pyrazole-5-carbonitrile (17 mg, 32%).

后处理

  1. customthe mixture was degassed under nitrogen in a vial
  2. customThe vial was sealed
  3. additionWater was added
  4. extractionthe mixture was extracted with CH2Cl2
  5. concentrationthe organic layer was concentrated
  6. customThe crude product was purified on silica

来源与证据

ORD记录
ord-d442e8d1950d489f8f597cfc1c626705
来源数据集
uspto-grants-2014_12
专利号
US08921402B2

反应笔记

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