Cesium carbonate → 4-Chloro-6-(6-methoxy-pyridin-3-yl)-2-methylsulfanyl-pyrimidine

HRID 216135

Reaction equation

HRID 216135 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][N:4]=1.[Cl:12][C:13]1[CH:18]=[C:17](Cl)[N:16]=[C:15]([S:20][CH3:21])[N:14]=1.C([O-])([O-])=O.[Cs+].[Cs+]>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:12][C:13]1[CH:18]=[C:17]([C:6]2[CH:5]=[N:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)[N:16]=[C:15]([S:20][CH3:21])[N:14]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 805314,6-Dichloro-2-(methylthio)pyrimidine2×HCID 2734368(6-Methoxypyridin-3-yl)boronic acid

Product 1

HCID 576361374-Chloro-6-(6-methoxy-pyridin-3-yl)-2-methylsulfanyl-pyrimidine

Reagents, catalysts & solvents 3

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

Procedure

A mixture of 2-methoxy-5-pyridyl-boronic acid (600 mg, 2.04 mmol, Intermediate (37), prepared according to the procedure described in J. Org. Chem., 67, 7541, 2002), 4,6-dichloro-2-methylsulfanyl-pyrimidine [700 mg, 3.59 mmol, Intermediate (29)], and Cs2CO3 (2.9 g, 8.97 mmol) in ethylene glycol dimethyl ether (8 mL) and water (2 mL) is degassed by bubbling with Argon gas for 5 minutes, and treated with tetrakis(triphenylphosphine)palladium(0) (207 mg, 0.18 mmol) at room temperature. After 3 hours at 85° C., the mixture is diluted with water (50 mL), and extracted twice with EtOAc (50 mL). The extracts are dried over magnesium sulfate, filtered, and concentrated to afford 4-chloro-6-(6-methoxy-pyridin-3-yl)-2-methylsulfanyl-pyrimidine [1.1 g, Intermediate (38)] as an oil. LCMS: RT=3.72 minutes, MS: 268 (M+H).

Workup

  1. customprepared
  2. customby bubbling with Argon gas for 5 minutes
  3. extractionextracted twice with EtOAc (50 mL)
  4. dry with materialThe extracts are dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-1da3546174374a378f542f919405334d
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Linked notes

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