Hydrochloric Acid → 4-Chloro-6-(4-fluorophenyl)thieno[2,3-d]pyrimidine

HRID 1396785Notes

Reaction equation

HRID 1396785 reaction equation
Br[C:2]1[S:11][C:5]2[N:6]=[CH:7][N:8]=[C:9]([Cl:10])[C:4]=2[CH:3]=1.[F:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1.C([O-])([O-])=O.[K+].[K+].Cl>O1CCOCC1.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:10][C:9]1[C:4]2[CH:3]=[C:2]([C:16]3[CH:17]=[CH:18][C:13]([F:12])=[CH:14][CH:15]=3)[S:11][C:5]=2[N:6]=[CH:7][N:8]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 122252616-Bromo-4-chlorothieno[2,3-d]pyrimidine

Product 1

HCID 866624414-Chloro-6-(4-fluorophenyl)thieno[2,3-d]pyrimidineYield 47.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

A solution of 6-bromo-4-chlorothieno[2,3-d]pyrimidine (0.12 g, 0.48 mmol), 4-fluorophenylboronic acid (67 mg, 0.48 mmol), K2CO3 (0.266 g, 1.92 mmol) and Pd(PPh3)4 in dioxane/H2O (3:1, 3 ml) was refluxed under N2 for 2 hours. After cooling to room temperature, 1N HCl was added slowly to neutralize the mixture to pH=7-8. The mixture was extracted with CH2Cl2, washed with water and brine and dried over Na2SO4. After removing the solvents under reduced pressure, the crude residue was purified by silica gel chromatography (hexane/EtOAc 30:1) to yield the title compound as a pale yellow solid (60 mg, 47%).

Workup

  1. extractionThe mixture was extracted with CH2Cl2
  2. washwashed with water and brine
  3. dry with materialdried over Na2SO4
  4. customAfter removing the solvents under reduced pressure
  5. customthe crude residue was purified by silica gel chromatography (hexane/EtOAc 30:1)

Sources & evidence

ORD record
ord-f8aea11eba95427d874f67aefe24f3b8
Source dataset
uspto-grants-2014_12
Patent number
US08901132B2

Reaction notes

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