Isopropanol → 4-Chloro-6-(3,4-dimethoxyphenyl)-2-(methylthio)pyrimidine

HRID 216151

反応式

HRID 216151 の反応式
[Cl:1][C:2]1[CH:7]=[C:6](Cl)[N:5]=[C:4]([S:9][CH3:10])[N:3]=1.[CH3:11][O:12][C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[CH:17][C:18]=1[O:19][CH3:20].C([O-])([O-])=O.[Cs+].[Cs+].C(O)(C)C>COCCOC.O.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>[Cl:1][C:2]1[CH:7]=[C:6]([C:16]2[CH:15]=[CH:14][C:13]([O:12][CH3:11])=[C:18]([O:19][CH3:20])[CH:17]=2)[N:5]=[C:4]([S:9][CH3:10])[N:3]=1

参加物

8

反応物 4

HCID 3776IsopropanolHCID 10796Cesium carbonateHCID 805314,6-Dichloro-2-(methylthio)pyrimidine2 回HCID 27347023,4-Dimethoxyphenylboronic acid2 回

生成物 1

HCID 576361464-Chloro-6-(3,4-dimethoxyphenyl)-2-(methylthio)pyrimidine収率 83.6%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒2 回HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
100 °C

実験手順

Argon is bubbled through a mixture of 4,6-dichloro-2-(methylthio)pyrimidine [4.98 g, 25.55 mmol, Intermediate (29)], 3,4-dimethoxyphenylboronic acid [3.874 g, 21.29 mmol, Intermediate (32)], and Cs2CO3 (17.34 g, 53.23 mmol) in ethylene glycol dimethyl ether (56 mL) and water (14 mL), for a period of 15 minutes. To this mixture is added tetrakis(triphenylphosphine)palladium (0) (1.22 g, 1.06 mmol) the reaction vessel is heated to 100° C. After stirring overnight the mixture is diluted with water (250 mL) and extracted three times with EtOAc (100 mL). The organic extracts are combined, washed with brine (100 mL), and dried over magnesium sulfate. The mixture is filtered and concentrated to provide a solid that is dissolved in boiling isopropyl alcohol (40 mL) and allowed to cool to ambient temperature. After standing for 24 hours the solid is collected by filtration, washed with cold isopropyl alcohol and dried under high vacuum to afford 4-chloro-6-(3,4-dimethoxy-phenyl)-2-methylsulfanyl-pyrimidine [5.28 g, 83.5%, Intermediate (48)].

後処理

  1. extractionextracted three times with EtOAc (100 mL)
  2. washwashed with brine (100 mL)
  3. dry with materialdried over magnesium sulfate
  4. filtrationThe mixture is filtered
  5. concentrationconcentrated
  6. customto provide a solid
  7. dissolutionthat is dissolved
  8. temperatureto cool to ambient temperature
  9. waitAfter standing for 24 hours
  10. filtrationthe solid is collected by filtration
  11. washwashed with cold isopropyl alcohol
  12. customdried under high vacuum

出典と根拠

ORDレコード
ord-ebeec63bcd6a4bdfb9ce05b0a1a3d940
出典データセット
uspto-grants-2012_06
特許番号
US08193183B2

関連ノート

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