Potassium Carbonate → HCID 58213608, compound

HRID 340194Notes

Reaction equation

HRID 340194 reaction equation
[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8](B2OC(C)(C)C(C)(C)O2)=[C:9]([NH:11]C(=O)OC(C)(C)C)[CH:10]=1)(=[O:4])=[O:3].Br[C:29]1[C:30]([C:35]#[N:36])=[N:31][CH:32]=[CH:33][CH:34]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.CO.ClCCl.O>[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]2=[C:29]3[C:30](=[C:35]([NH2:36])[N:11]=[C:9]2[CH:10]=1)[N:31]=[CH:32][CH:33]=[CH:34]3)(=[O:3])=[O:4]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 8176943-Bromopyridine-2-carbonitrileHCID 66892334HCID 66892334, compound

Product 1

HCID 58213608HCID 58213608, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of tert-butyl 5-(methylsulfonyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate (from step 3) (1.0 eq.) and 3-bromopicolino-nitrile (1.0 eq.) in toluene (0.24 M) was mixed with tetrakis(triphenyl-phosphine)palladium (5 mol %) and 2N aqueous potassium carbonate solution (4.0 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 0-5% methanol in dichloromethane to give a solid which was then triturated in 1:1 hexane/ethyl acetate to give 8-(methylsulfonyl)benzo[f][1,7]naphthyridin-5-amine 1H NMR (acetone d-6): δ 9.16 (d, 1H), 9.03 (d, 1H), 8.71 (d, 1H), 8.11 (s, 1H), 7.93-7.96 (dd, 1H), 7.81 (d, 1H), 7.0 (br, 2H), 3.19 (s, 3H). LRMS [M+H]=274.1

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 which
  9. customwas then triturated in 1:1 hexane/ethyl acetate

Sources & evidence

ORD record
ord-4dcbb584b7964f24b29ead2b71ed1027
Source dataset
uspto-grants-2014_11
Patent number
US08895577B2

Reaction notes

Loading…