Potassium Phosphate, Tribasic → (2-(5-bromo-1((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-3-ylamino)-1-phenyl-1H-benzo[d]imidazol-5-yl)methanol

HRID 2068276Notes

Reaction equation

HRID 2068276 reaction equation
[Br:1][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]2I.[NH2:20][C:21]1[N:25]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:24]2[CH:32]=[CH:33][C:34]([CH2:36][OH:37])=[CH:35][C:23]=2[N:22]=1.CN[C@@H]1CCCC[C@H]1NC.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCCC1.C(OCC)(=O)C.[Cu]I>[Br:1][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:20][C:21]1[N:25]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:24]2[CH:32]=[CH:33][C:34]([CH2:36][OH:37])=[CH:35][C:23]=2[N:22]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 21899153(2-amino-1-phenyl-1H-benzo[d]imidazol-5-yl)methanolHCID 583172565-Bromo-3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole

Product 1

HCID 67253458(2-(5-bromo-1((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-3-ylamino)-1-phenyl-1H-benzo[d]imidazol-5-yl)methanolYield 7.3%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 5-bromo-3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (906 mg, 0.00200 mol), (2-amino-1-phenyl-1H-benzoimidazol-5-yl)methanol (435 mg, 0.00182 mol), copper(I) iodide (110 mg, 0.00056 mol), trans-N1,N2-dimethylcyclohexane-1,2-diamine (160 mg, 0.0011 mol) and potassium phosphate (772 mg, 0.00364 mol) in tetrahydrofuran (19.4 mL) was stirred under argon sparging until a greenish suspension formed. The mixture was then microwaved at 140° C. for 3 hours. The reaction mixture was diluted with ethyl acetate and washed with 5% citric acid, saturated sodium bicarbonate, brine, dried over magnesium sulfate and concentrated. The residue was purified by flash chromatography using 0-100% ethyl acetate-hexanes. The product was taken up in ethyl acetate, washed with 1N HCl to remove residual copper and rechromatograped to give 75 mg of product.

Workup

  1. customformed
  2. customThe mixture was then microwaved at 140° C. for 3 hours
  3. washwashed with 5% citric acid, saturated sodium bicarbonate, brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography
  7. washwashed with 1N HCl
  8. customto remove residual copper

Sources & evidence

ORD record
ord-8ebbd515f52e42528da488b6636751ef
Source dataset
uspto-grants-2012_10
Patent number
US08293923B2

Reaction notes

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