Dichloromethane → HCID 67253665, compound

HRID 2068273Notes

Reaction equation

HRID 2068273 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]([CH2:25][CH2:26][CH2:27][O:28][Si:29]([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30])[C:23]2[CH:36]=[CH:37][CH:38]=[CH:39][C:22]=2[N:21]=1.ClCCl.C(=O)([O-])[O-].[Na+].[Na+].O1[CH2:54][CH2:53][O:52][CH2:51]C1>O>[Si:29]([O:28][CH2:27][CH2:26][CH2:25][N:24]1[C:23]2[CH:36]=[CH:37][CH:38]=[CH:39][C:22]=2[N:21]=[C:20]1[NH:19][C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([C:4]3[CH:8]=[N:7][CH:11]=[CH:54][C:53]=3[O:52][CH3:51])[CH:3]=2)[N:7]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[N:6]=1)([C:32]([CH3:34])([CH3:35])[CH3:33])([CH3:31])[CH3:30]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 67255489HCID 67255489, compound

Product 1

HCID 67253665HCID 67253665, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 5-bromo-N-(1-(3-(tert-butyldimethylsilyloxy)propyl)-1H-benzo[d]imidazol-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-3-amine (from Step 1: 191 mg, 0.000303 mol), 4-methoxypyridin-3-yl-3-boronic acid (64 mg, 0.00042 mol) and (1,1′-bis(diphenylphosphino)-ferrocene)dichloropalladium(II), complexed with dichloromethane (1:1) (41 mg, 0.000050 mol), was dissolved in 1,4-dioxane (3.04 mL). To this mixture was added 2.0 M sodium carbonate in water (0.76 mL) with stirring. The mixture was flushed with argon sealed and heated at 110° C. After 3 hours, the mixture was diluted with methylene chloride, washed with water and brine, the organic phase dried over magnesium sulfate, filtered, and concentrated. The residue was dissolved in methylene chloride and purified by flash chromatography (50-100% ethyl acetate-0.3% triethylamine in hexanes) to give 132 mg (66%) of the title compound.

Workup

  1. customThe mixture was flushed with argon
  2. customsealed
  3. additionthe mixture was diluted with methylene chloride
  4. washwashed with water and brine
  5. dry with materialthe organic phase dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in methylene chloride
  9. custompurified by flash chromatography (50-100% ethyl acetate-0.3% triethylamine in hexanes)

Sources & evidence

ORD record
ord-62081b7f6ed64642aaf59754521de9f3
Source dataset
uspto-grants-2012_10
Patent number
US08293923B2

Reaction notes

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