Potassium Carbonate → 3-(Tert-butyldimethylsilyloxy)benzo[f][1,7]naphthyridin-5-amine

HRID 1259067Notes

Reaction equation

HRID 1259067 reaction equation
C(OC([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1B(O)O)=O)(C)(C)C.Br[C:19]1[C:20]([C:33]#[N:34])=[N:21][C:22]([O:25][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27])=[CH:23][CH:24]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.CO.ClCCl.O>[Si:26]([O:25][C:22]1[CH:23]=[CH:24][C:19]2[C:20](=[C:33]([NH2:34])[N:8]=[C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]3=2)[N:21]=1)([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 2773226(2-BOC-aminophenyl)boronic acidHCID 668757543-Bromo-6-(tert-butyldimethylsilyloxy)picolinonitrile

Product 1

HCID 671176883-(Tert-butyldimethylsilyloxy)benzo[f][1,7]naphthyridin-5-amine

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 2-(tert-butoxycarbonylamino)phenylboronic acid (1.0 eq.) and 3-bromo-6-(tert-butyldimethylsilyloxy)picolinonitrile (from step 3) (1.0 eq.) in toluene/ethanol (10:1, 0.2 M) was mixed with tetrakis(triphenyl-phosphine)palladium (5 mol %) and 2N aqueous potassium carbonate solution (2.0 eq.). The reaction was heated to 100° C. and stirred overnight. After cooling to ambient temperature, the reaction content was diluted with 2% methanol in dichloromethane and water. The two phases were separated, and the aqueous layer was extracted twice with 2% methanol in dichloromethane. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vacuo. The crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-50% ethyl acetate in hexane to give a solid.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. customThe two phases were separated
  3. extractionthe aqueous layer was extracted twice with 2% methanol in dichloromethane
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous MgSO4
  6. concentrationconcentrated en vacuo
  7. customThe crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO)
  8. customto give a solid

Sources & evidence

ORD record
ord-a7a99d13c4024860b90e1ae36e164eba
Source dataset
uspto-grants-2013_06
Patent number
US08466167B2

Reaction notes

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