1,4-Dioxane → HCID 89478924, compound

HRID 871179Notes

Reaction equation

HRID 871179 reaction equation
Br[C:2]1[C:7]2[S:8][CH:9]=[CH:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.Cl.[CH3:12][C:13]1[CH:18]=[CH:17][N:16]=[CH:15][C:14]=1B(O)O.O1CCOCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(Cl)Cl.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>[S:8]1[CH:9]=[CH:10][C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([C:14]3[CH:15]=[N:16][CH:17]=[CH:18][C:13]=3[CH3:12])[C:7]1=2

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 120455387-Bromobenzo[b]thiopheneHCID 66524085HCID 66524085, compound

Product 1

HCID 89478924HCID 89478924, compoundYield 89.5%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

A vessel capable of sealing was charged with a mixture of 7-bromobenzo[b]thiophene (370 mg, 1.736 mmol), 4-methylpyridin-3-ylboronic acid HCl (361 mg, 2.084 mmol), PdCl2(dppf)-CH2Cl2 adduct (70.9 mg, 0.087 mmol), dioxane (8 mL), and a 2.0 M aqueous solution of K3PO4 (3.47 mL, 6.95 mmol) and was purged with nitrogen for 10 min. The vessel was sealed and heated at 90° C. for 10 hours. Upon cooling, the reaction mixture was diluted with CH2Cl2 and filtered with CH2Cl2/MeOH washing. The filtrate was concentrated under reduced pressure. The residue was dissolved in CH2Cl2 and washed with water, brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude material was purified by BIOTAGE® eluting with 10%-40% EtOAc/CH2Cl2 at 30 mL/min. Concentration of appropriate fractions provided the title compound (350 mg, 89% yield). LC/MS: Example 111A @ 1.50 min (RT) (Condition G). MS (ES): m/z=226.12.1 [M+H]+. 1H NMR (400 MHz, CDCl3) δ ppm 8.50-8.64 (2 hr, m), 7.89 (1 hr, dd, J=7.93, 1.13 Hz), 7.40-7.55 (3 hr, m), 7.25-7.33 (1 hr, m), 7.22 (1 hr, d, J=6.30 Hz), 2.21 (3 hr, s).

Workup

  1. customThe vessel was sealed
  2. temperatureUpon cooling
  3. filtrationfiltered with CH2Cl2/MeOH washing
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. dissolutionThe residue was dissolved in CH2Cl2
  6. washwashed with water, brine
  7. dry with materialdried over anhydrous Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was purified by BIOTAGE®
  10. washeluting with 10%-40% EtOAc/CH2Cl2 at 30 mL/min

Sources & evidence

ORD record
ord-557da782fb9e458cb15095d775cca4de
Source dataset
uspto-grants-2015_03
Patent number
US08969586B2

Reaction notes

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