Potassium Carbonate → HCID 44230478, compound

HRID 340195Notes

Reaction equation

HRID 340195 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][C:10]=2[NH:19]C(=O)OC(C)(C)C)O1.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>[F:16][C:15]([F:17])([F:18])[C:12]1[CH:13]=[CH:14][C:9]2=[C:29]3[C:30](=[C:35]([NH2:36])[N:19]=[C:10]2[CH:11]=1)[N:31]=[CH:32][CH:33]=[CH:34]3

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 8176943-Bromopyridine-2-carbonitrileHCID 56973310HCID 56973310, compound

Product 1

HCID 44230478HCID 44230478, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of tert-butyl 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)phenylcarbamate (from step 2) (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 product was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-40% ethyl acetate in toluene to give a solid which was then triturated in 10% ethyl acetate in hexane to give 8-(trifluoromethyl)benzo[f][1,7]naphthyridin-5-amine. 1H NMR (acetone d-6): δ 9.13 (d, 1H), 9.00 (d, 1H), 8.67 (d, 1H), 7.91-7.94 (dd, 1H), 7.86 (s, 1H), 7.58 (d, 1H), 6.9 (br, 2H). LRMS [M+H]=264.1

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 product was purified by flash chromatography on a COMBIFLASH® system (ISCO)
  8. customto give a solid which
  9. customwas then triturated in 10% ethyl acetate in hexane

Sources & evidence

ORD record
ord-632149909f7e45bd8c576f01d2a48844
Source dataset
uspto-grants-2014_11
Patent number
US08895577B2

Reaction notes

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