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

HRID 2110679

Reaction equation

HRID 2110679 reaction equation
[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

Participants

8

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

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)].

Workup

  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

Sources & evidence

ORD record
ord-4d37cf74eb7944c39c60be4d1172d3f9
Source dataset
uspto-grants-2009_04
Patent number
US07517889B2

Linked notes

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