Benzo(B)Thiophene-2-Boronic Acid → HCID 86710555, compound

HRID 1027162Notes

Reaction equation

HRID 1027162 reaction equation
[Cl:1][C:2]1[N:3]=[N:4][C:5](Cl)=[CH:6][CH:7]=1.C([O-])([O-])=O.[Na+].[Na+].[S:15]1[C:19](B(O)O)=[CH:18][C:17]2[CH:23]=[CH:24][CH:25]=[CH:26][C:16]1=2.C(Cl)Cl>COCCOC.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]>[S:15]1[C:19]([C:5]2[N:4]=[N:3][C:2]([Cl:1])=[CH:7][CH:6]=2)=[CH:18][C:17]2[CH:23]=[CH:24][CH:25]=[CH:26][C:16]1=2

Participants

8

Reactant 4

HCID 2359Benzo(B)Thiophene-2-Boronic AcidHCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 673313,6-Dichloropyridazine

Product 1

HCID 86710555HCID 86710555, compoundYield 34%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

To 3,6-dichloropyridazine (4.18 g, 28.1 mmol) and Na2CO3 (8.93 g, 84 mmol) in DME (100 mL) and water (25 mL) was added benzo[b]thiophen-2-ylboronic acid (5 g, 28.1 mmol) and PdCl2(dppf).CH2Cl2 (0.69 g, 0.84 mmol). The reaction was evacuated under vacuum and purged with N2 3×. The reaction was heated at 85° C. for 18 h and cooled to RT. The crude product was filtered through celite and was rinsed with EtOAc followed by CH2Cl2. The crude filtrate was concentrated under vacuum and diluted in CH2Cl2 and water. The organic layer was separated, and the remaining emulsion was acidified with 1 M HCl and extracted with EtOAc. The combined organic layers were washed with water, brine, dried over MgSO4, filtered, and concentrated. The crude product was purified by silica gel chromatography. The product was partially concentrated to provide a precipitate which was filtered to give 3-(benzo[b]thiophen-2-yl)-6-chloropyridazine (2.36 g) as a light yellow solid. The filtrate was recrystallized from CH3CN to give 3-(benzo[b]thiophen-2-yl)-6-chloropyridazine (0.46 g). LCMS Rt=1.57 minutes (condition B); (M+1)=247.1.

Workup

  1. customThe reaction was evacuated under vacuum
  2. custompurged with N2 3×
  3. temperaturecooled to RT
  4. filtrationThe crude product was filtered through celite
  5. washwas rinsed with EtOAc
  6. concentrationThe crude filtrate was concentrated under vacuum
  7. additiondiluted in CH2Cl2
  8. customThe organic layer was separated
  9. extractionextracted with EtOAc
  10. washThe combined organic layers were washed with water, brine
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe crude product was purified by silica gel chromatography
  15. concentrationThe product was partially concentrated
  16. customto provide a precipitate which
  17. filtrationwas filtered

Sources & evidence

ORD record
ord-e3bcb258db404b11981b69014f1ff9db
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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