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

HRID 2234113Notes

Reaction equation

HRID 2234113 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]([Br:32])[CH:30]=2)[CH:25]=[C:24]1B1OC(C)(C)C(C)(C)O1)=[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]([Br: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 56973297Tert-butyl 6-bromo-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-indole-1-carboxylate

Product 1

HCID 686373616-Bromo-2-(3-methoxy-6-pyridin-4-yl-pyridazin-4-yl)-indole-1-carboxylic acid tert-butyl esterYield 96.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

1.075 g 4-Iodo-3-methoxy-6-pyridin-4-yl-pyridazine, 1.45 g 6-bromo-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-indole-1-carboxylic acid tert-butyl ester, 4.48 g cesium carbonate, and 140 mg [1,1′-bis(diphenylphosphino)ferrocene]dichloro-palladium(II) complex with dichloromethane (1:1) are dissolved in a mixture of 30 mL dioxane and 8.8 mL water. Argon is bubbled through the solution for 5 minutes. The mixture is heated to reflux for 2 hours. After diluting with EtOAc, the organic phase is washed with water and brine, dried with MgSO4 and concentrated in vacuo. Purification on silica (Flashmaster, methylenechloride/MeOH) gives 1.59 g (96%) 6-bromo-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 mixture is heated
  3. temperatureto reflux for 2 hours
  4. additionAfter diluting with EtOAc
  5. washthe organic phase is washed with water and brine
  6. dry with materialdried with MgSO4
  7. concentrationconcentrated in vacuo
  8. customPurification on silica (Flashmaster, methylenechloride/MeOH)

Sources & evidence

ORD record
ord-14254e7cb1a24e9595a8eb8fca52dc58
Source dataset
uspto-grants-2010_05
Patent number
US07709466B2

Reaction notes

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