Dichloromethane → 6-Hydroxy-2-(3-methoxy-6-pyridin-4-yl-pyridazin-4-yl)-indole-1-carboxylic acid tert-butyl ester

HRID 2234088Notes

Reaction equation

HRID 2234088 reaction equation
I[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=2)[N:5]=[N:4][C:3]=1[O:14][CH3:15].[C:16]([O:20][C:21]([N:23]1[C:31]2[C:26](=[CH:27][CH:28]=[C:29]([O:32][Si](C(C)(C)C)(C)C)[CH:30]=2)[CH:25]=[C:24]1B(O)O)=[O:22])([CH3:19])([CH3:18])[CH3:17].C(=O)([O-])[O-].[Cs+].[Cs+].ClCCl>O1CCOCC1.O>[C:16]([O:20][C:21]([N:23]1[C:31]2[C:26](=[CH:27][CH:28]=[C:29]([OH:32])[CH:30]=2)[CH:25]=[C:24]1[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=2)[N:5]=[N:4][C:3]=1[O:14][CH3:15])=[O:22])([CH3:19])([CH3:17])[CH3:18]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 230924634-Iodo-3-methoxy-6-pyridin-4-yl-pyridazineHCID 230924981-(1,1-Dimethylethyl) 2-borono-6-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-1H-indole-1-carboxylate

Product 1

HCID 1363396366-Hydroxy-2-(3-methoxy-6-pyridin-4-yl-pyridazin-4-yl)-indole-1-carboxylic acid tert-butyl esterYield 95%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

600 mg 4-Iodo-3-methoxy-6-pyridin-4-yl-pyridazine, 974 mg 1-(tert-butoxycarbonyl)-6-(tert-butyldimethylsiloxy)indole-2-boronic acid, 2.5 g cesium carbonate, and 78 mg [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) are dissolved in a mixture of 18 mL dioxane and 5.4 mL water. Argon is bubbled through the solution for 5 minutes. The mixtures is heated to reflux for 2 hours. After diluting with EtOAc, the organic phase is ished with water and brine, dried with MgSO4 and concentrated in vacuo. The crude product is dissolved in 30 mL THF. After addition of 1.51 g tetrabutylammonium fluoride trihydrate, the red solution is stirred for 2 hours. The reaction mixture is diluted with EtOAc, ished with saturated aqueous ammonium chloride, water, and brine, dried with MgSO4 and concentrated in vacuo. Purification by HPLC afforded 760 mg (95%) 6-hydroxy-2-(3-methoxy-6-pyridin-4-yl-pyridazin-4-yl)-indole-1-carboxylic acid tert-butyl ester.

Workup

  1. customArgon is bubbled through the solution for 5 minutes
  2. temperatureThe mixtures is heated
  3. temperatureto reflux for 2 hours
  4. additionAfter diluting with EtOAc
  5. dry with materialdried with MgSO4
  6. concentrationconcentrated in vacuo
  7. dissolutionThe crude product is dissolved in 30 mL THF
  8. additionAfter addition of 1.51 g tetrabutylammonium fluoride trihydrate
  9. additionThe reaction mixture is diluted with EtOAc
  10. dry with materialdried with MgSO4
  11. concentrationconcentrated in vacuo
  12. customPurification by HPLC

Sources & evidence

ORD record
ord-cbe139c0ccf84feb820b16ea16bb62f0
Source dataset
uspto-grants-2010_05
Patent number
US07709466B2

Reaction notes

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