1,4-Dioxane → 7-Chloro-3-(2-chloro-4-fluorophenyl)thieno[3,2-b]pyridine

HRID 871174Notes

Reaction equation

HRID 871174 reaction equation
Br[C:2]1[C:6]2=[N:7][CH:8]=[CH:9][C:10]([Cl:11])=[C:5]2[S:4][CH:3]=1.[Cl:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1B(O)O.O1CCOCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[Cl:11][C:10]1[CH:9]=[CH:8][N:7]=[C:6]2[C:2]([C:14]3[CH:15]=[CH:16][C:17]([F:19])=[CH:18][C:13]=3[Cl:12])=[CH:3][S:4][C:5]=12

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 177502292-Chloro-4-fluorobenzeneboronic acidHCID 867304243-Bromo-7-chlorothieno[3,2-b]pyridine

Product 1

HCID 867304277-Chloro-3-(2-chloro-4-fluorophenyl)thieno[3,2-b]pyridineYield 80.2%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A vessel capable of sealing was charged with a mixture of 3-bromo-7-chlorothieno[3,2-b]pyridine (260 mg, 1.046 mmol), 2-chloro-4-fluorophenylboronic acid (274 mg, 1.569 mmol), PdCl2(dppf)-CH2Cl2 adduct (42.7 mg, 0.0.052 mmol), dioxane (8 mL), and a 2.0 M aqueous solution of K3PO4 (1.6 mL, 3.14 mmol) and was purged with nitrogen for 10 min. The vessel was sealed and heated at 90° C. for 3 h. Upon cooling, the reaction mixture was diluted with water and extracted with CH2Cl2. The combined organics were washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude material was purified by BIOTAGE® eluting with 60%-100% CH2Cl2/hexanes at 30 mL/min. Concentration of appropriate fractions provided the title compound (250 mg, 80% yield) as a white solid. LC/MS: Example 103A @ 3.58 min (RT) (Condition G). MS (ES): m/z=297.89, [M+H]+.

Workup

  1. customThe vessel was sealed
  2. temperatureUpon cooling
  3. extractionextracted with CH2Cl2
  4. washThe combined organics were washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified by BIOTAGE®
  8. washeluting with 60%-100% CH2Cl2/hexanes at 30 mL/min

Sources & evidence

ORD record
ord-0b9dab894cac49b19fcbbece98fbd495
Source dataset
uspto-grants-2015_03
Patent number
US08969586B2

Reaction notes

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