Dichloromethane → Thieno[3,2-d]pyrimidine-6-carboxylic acid, 7-(4-fluorophenyl)-2-(methylthio)-, methyl ester

HRID 518791Notes

Reaction equation

HRID 518791 reaction equation
[CH3:1][S:2][C:3]1[N:4]=[CH:5][C:6]2[S:11][C:10]([C:12]([O:14][CH3:15])=[O:13])=[C:9](OS(C(F)(F)F)(=O)=O)[C:7]=2[N:8]=1.[F:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1.CC(N=P(N1CCCC1)(N1CCCC1)N1CCCC1)(C)C.ClCCl>O1CCOCC1.Cl[Pd]Cl>[F:24][C:25]1[CH:30]=[CH:29][C:28]([C:9]2[C:7]3[N:8]=[C:3]([S:2][CH3:1])[N:4]=[CH:5][C:6]=3[S:11][C:10]=2[C:12]([O:14][CH3:15])=[O:13])=[CH:27][CH:26]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 2856454-Fluorophenylboronic acidHCID 3856267tert-Butylimino-tri(pyrrolidino)phosphoraneHCID 86697952HCID 86697952, compound

Product 1

HCID 86697960Thieno[3,2-d]pyrimidine-6-carboxylic acid, 7-(4-fluorophenyl)-2-(methylthio)-, methyl esterYield 78.4%

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 200 mg of methyl 2-(methylsulfanyl)-7-{[(trifluoromethyl)sulfonyl]oxy}thieno[3,2-d]pyrimidine-6-carboxylate 4 (example 1), 216 mg of 4-fluorophenylboronic acid, 19 mg of dichloropalladium (dppf) and 322 mg of BTPP in 2.5 ml of dioxane under argon is microwave-heated at 120° C. in a sealed tube for 1 h. The medium is taken up with dichloromethane and filtered. The organic phase is washed three times with water, then dried over magnesium sulfate, filtered, and then concentrated under vacuum so as to give a yellow solid. The crude is purified on 80 g of silica, elution being carried out with 0-20% of methanol in dichloromethane, so as to obtain 135 mg of methyl 7-(4-fluorophenyl)-2-(methylsulfanyl)thieno[3,2-d]pyrimidine-6-carboxylate in the form of a yellow solid.

Workup

  1. filtrationfiltered
  2. washThe organic phase is washed three times with water
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum so as
  6. customto give a yellow solid
  7. customThe crude is purified on 80 g of silica, elution

Sources & evidence

ORD record
ord-6866c4218d694f1fa1f171f7a538c073
Source dataset
uspto-grants-2015_08
Patent number
US09115140B2

Reaction notes

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