Dichloromethane → (1-cyclohexyl-2-(5-(4-methoxypyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-3-ylamino)-1H-benzo[d]imidazol-5-yl)methanol

HRID 2068288Notes

Reaction equation

HRID 2068288 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[N:6]=[C:5]2[NH:19][C:20]1[N:24]([CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)[C:23]2[CH:31]=[CH:32][C:33]([CH2:35][OH:36])=[CH:34][C:22]=2[N:21]=1.[CH3:37][O:38][C:39]1[CH:44]=[CH:43][N:42]=[CH:41][C:40]=1B(O)O.ClCCl.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>O>[CH:25]1([N:24]2[C:23]3[CH:31]=[CH:32][C:33]([CH2:35][OH:36])=[CH:34][C:22]=3[N:21]=[C:20]2[NH:19][C:5]2[C:4]3[C:8](=[CH:9][CH:10]=[C:2]([C:40]4[CH:41]=[N:42][CH:43]=[CH:44][C:39]=4[O:38][CH3:37])[CH:3]=3)[N:7]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:17])([CH3:18])[CH3:16])[N:6]=2)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1

Participants

7

Reactant 5

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 27625564-Methoxypyridine-3-boronic acidHCID 67255070(2-(5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-3-ylamino)-1-cyclohexyl-1H-benzo[d]imidazol-5-yl)methanol

Product 1

HCID 67253029(1-cyclohexyl-2-(5-(4-methoxypyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-3-ylamino)-1H-benzo[d]imidazol-5-yl)methanolYield 16.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

In a small microwave tube was added (2-(5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-3-ylamino)-1-cyclohexyl-1H-benzo[d]imidazol-5-yl)methanol (164 mg, 0.000287 mol), 4-methoxypyridin-3-ylboronic acid (79.1 mg, 0.000517 mol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II),complex with dichloromethane (1:1) (47 mg, 0.000057 mol). To this mixture was added 1,4-dioxane (4.3 mL, 0.055 mol) and the resultant mixture was stirred under an argon atmosphere. To this mixtrure was then added 2 M sodium carbonate in water (700 uL) and the reaction mixture was microwaved for 21 minutes at 120° C. The reaction mixture filtered through a syringe filter cartridge and the cartridge washed 3 times with methanol. The residue after concentration was purified by flash chromatography using a 40 g silica gel cartridge and 10-60% ethyl acetate/hexane gradient. The product fractions were concentrated to give the title compound (29 mg).

Workup

  1. customthe reaction mixture was microwaved for 21 minutes at 120° C
  2. filtrationThe reaction mixture filtered through a syringe
  3. filtrationfilter cartridge
  4. washthe cartridge washed 3 times with methanol
  5. concentrationThe residue after concentration
  6. customwas purified by flash chromatography
  7. concentrationThe product fractions were concentrated

Sources & evidence

ORD record
ord-2980718fc3bb424f970f54cfc8e389d9
Source dataset
uspto-grants-2012_10
Patent number
US08293923B2

Reaction notes

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