Sodium Bicarbonate → 5-benzyloxy-3-(1H-indol-2-yl)-1H-indazole

HRID 1726047Notes

Reaction equation

HRID 1726047 reaction equation
C(OC([N:8]1[C:16]2[C:11](=[CH:12][C:13]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[CH:14][CH:15]=2)[C:10](I)=[N:9]1)=O)(C)(C)C.C(OC([N:33]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH:35]=[C:34]1B1OB(C2CC3C(=CC=CC=3)N2C(OC(C)(C)C)=O)O1)=O)(C)(C)C.C(=O)(O)[O-].[Na+]>>[CH2:18]([O:17][C:13]1[CH:12]=[C:11]2[C:16](=[CH:15][CH:14]=1)[NH:8][N:9]=[C:10]2[C:34]1[NH:33][C:41]2[C:36]([CH:35]=1)=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

4

Reactant 3

HCID 516892Sodium BicarbonateHCID 575624111H-Indazole-1-carboxylic acid, 3-iodo-5-(phenylmethoxy)-, 1,1-dimethylethyl esterHCID 688444152-[4-(1-tert-butoxycarbonyl-2,3-dihydro-1H-indol-2-yl)-1,3,2,4-dioxadiboretan-2-yl]indole-1-carboxylic acid tert-butyl ester

Product 1

HCID 1360560025-benzyloxy-3-(1H-indol-2-yl)-1H-indazoleYield 80.9%

Procedure

Stage Ib: A suspension of 3.23 g of 5-benzyloxy-3-iodoindazole-1-carboxylic acid tert-butyl ester, 7.31 g of 2-[4-(1-tert-butoxycarbonyl-2,3-dihydro-1H-indol-2-yl)-1,3,2,4-dioxadiboretan-2-yl]indole-1-carboxylic acid tert-butyl ester, 2.07 g of palladium tetrakistriphenylphosphine and 11 ml of a saturated aqueous sodium bicarbonate solution is heated at reflux for approximately two hours and then at ambient temperature overnight. The reaction medium is filtered through paper, and the filtrate is then diluted with 150 ml of ethyl acetate. The organic phase is washed with 200 ml of distilled water. The aqueous phase is extracted with 2×150 ml of ethyl acetate. The organic phases are combined and washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate and filtered. The solvent is evaporated off under vacuum in a rotary evaporator. The resulting crude product is purified by flash chromatography on silica 70-200 μm, eluent: cyclohexane/ethyl acetate gradient 95:5 to 70:30 to obtain 1.97 g of 5-benzyloxy-3-(1H-indol-2-yl)-1H-indazole.

Workup

  1. temperatureis heated
  2. temperatureat reflux for approximately two hours
  3. customat ambient temperature
  4. customovernight
  5. filtrationThe reaction medium is filtered through paper
  6. additionthe filtrate is then diluted with 150 ml of ethyl acetate
  7. washThe organic phase is washed with 200 ml of distilled water
  8. extractionThe aqueous phase is extracted with 2×150 ml of ethyl acetate
  9. washwashed with a saturated aqueous sodium chloride solution
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. customThe solvent is evaporated off under vacuum in a rotary evaporator
  13. customThe resulting crude product is purified by flash chromatography on silica 70-200 μm, eluent

Sources & evidence

ORD record
ord-2246b1035bc34781b8b6da282b423693
Source dataset
uspto-grants-2009_02
Patent number
US07491710B2

Reaction notes

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