2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 73438582, compound

HRID 2284583Notes

Reaction equation

HRID 2284583 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]3[CH:15]=[C:16]4[C:20](=[CH:21][CH:22]=3)[NH:19][N:18]=[CH:17]4)=[CH:12][CH:11]=[CH:10][N:9]=2)=[CH:4][C:3]=1C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[Br-].CC1[N:65]=C([Zn+])C=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:4][C:3]1[N:65]=[C:5]([C:8]2[C:13]([C:14]3[CH:15]=[C:16]4[C:20](=[CH:21][CH:22]=3)[NH:19][N:18]=[CH:17]4)=[CH:12][CH:11]=[CH:10][N:9]=2)[CH:6]=[CH:7][CH:2]=1

Participants

5

Reactant 3

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 73670948HCID 73670948, compoundHCID 178426002HCID 178426002, compound

Product 1

HCID 73438582HCID 73438582, compoundYield 47.4%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
65 °C

Procedure

A vial with a piercable teflon cap containing a magetic stir was charged with 5-[2-(4-fluoro-3-methylphenyl)pyridin-3-yl]-1H-indazole (0.2 g, 0.87 mmol), Pd2(dba)3(30 mg, 0.03 mmol) and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (XPHOS, 60 mg, 0.13 mmol) under argon atmosphere. 6-Methyl-2-pyridylzinc bromide (0.5 M in THF, 4.0 mL, 2 mmol) was added to above reactants and degassed under vacuum. After three degas cycles, the reaction mixture was heated at 65° C. under argon. After 6 h, the reaction mixture was cooled to the room temperature and diluted with Rochelle salt (5 mL) and concentrated to remove the volatiles. The concentrated aqueous solution was diluted with EtOAc (30 mL) and separated the organic layer. Aqueous solution was further extracted with EtOAc (30 mL). Combined organic layers washed with aq. NaCl (10 mL), stirred over MgSO4, and filtered through a pad of Florosil/celite. The filtrate was concentrated and purified by preparative HPLC. The collected fractions were concentrated, diluted with water and neutralized with aq. NaHCO3. The resultant solid formed was collected by filtration and dried to provide 5-(2-(6-Methylpyridin-2-yl)pyridin-3-yl)-1H-indazole (118 mg, 47%) as a white solid. 1H NMR (DMSO-d6): δ 13.01 (s, 1H), 8.63 (dd, 1H, J=0.8 and 4.7 Hz), 7.99 (s, 1H), 7.89 (d, 1H, J=7.9 Hz), 7.57 (app d, 2H, J=8.5 Hz), 7.51 (dd, 1H, J=4.9 and 7.6 Hz), 7.34 (d, 1H, J=8.8 Hz), 7.26 (d, 1H, J=7.6 Hz), 7.07 (d, 1H, J=7.6 Hz), 6.97 (d, 1H, J=8.8 Hz), 2.15 (s, 3H).LCMS: rt 2.13 min (B), purity 97%, MS (m/e) 287 (MH+).

Workup

  1. additioncontaining
  2. customdegassed under vacuum
  3. customAfter three degas cycles
  4. temperaturethe reaction mixture was cooled to the room temperature
  5. additiondiluted with Rochelle salt (5 mL)
  6. concentrationconcentrated
  7. customto remove the volatiles
  8. additionThe concentrated aqueous solution was diluted with EtOAc (30 mL)
  9. customseparated the organic layer
  10. extractionAqueous solution was further extracted with EtOAc (30 mL)
  11. washCombined organic layers washed with aq. NaCl (10 mL)
  12. stirringstirred over MgSO4
  13. filtrationfiltered through a pad of Florosil/celite
  14. concentrationThe filtrate was concentrated
  15. custompurified by preparative HPLC
  16. concentrationThe collected fractions were concentrated
  17. additiondiluted with water and neutralized with aq. NaHCO3
  18. customThe resultant solid formed
  19. filtrationwas collected by filtration
  20. customdried

Sources & evidence

ORD record
ord-d5b35f15ad7a44a3aa7fe38eea34b408
Source dataset
uspto-grants-2015_09
Patent number
US09145433B2

Reaction notes

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