Potassium Carbonate → HCID 66890944, compound

HRID 1479594Notes

Reaction equation

HRID 1479594 reaction equation
[CH3:1][O:2][CH2:3][C:4]1[CH:5]=[CH:6][C:7](B2OC(C)(C)C(C)(C)O2)=[C:8]([NH:10]C(=O)OC(C)(C)C)[CH:9]=1.Br[C:28]1[C:29]([C:34]#[N:35])=[N:30][CH:31]=[CH:32][CH:33]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.CO.C(Cl)Cl.O>[CH3:1][O:2][CH2:3][C:4]1[CH:5]=[CH:6][C:7]2=[C:28]3[C:29](=[C:34]([NH2:35])[N:10]=[C:8]2[CH:9]=1)[N:30]=[CH:31][CH:32]=[CH:33]3

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 8176943-Bromopyridine-2-carbonitrileHCID 66893225HCID 66893225, compound

Product 1

HCID 66890944HCID 66890944, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of tert-butyl 5-(methoxymethyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate (from the previous step) (1.0 eq.) and 3-bromopicolino-nitrile (1.0 eq.) in toluene (0.44 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 mixture was diluted with 2% MeOH in DCM and water. The two phases were separated, and the aqueous layer was extracted twice with 2% MeOH in DCM. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vaccuo. The crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-100% EtOAc/Hexanes to give 8-(methoxymethyl)benzo[f][1,7]naphthyridin-5-amine as a white solid: 1H NMR (methanol-d4): δ 8.97 (dd, 1H), 8.91 (dd, 1H), 8.41 (dd, 1H), 7.83 (dd, 1H), 7.59 (d, 1H), 7.37 (dd, 1H), 4.62 (s, 2H), 3.45 (s, 3H). LRMS [M+H]=240.1.

Workup

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

Sources & evidence

ORD record
ord-de839c26775444db93aefbe356afb432
Source dataset
uspto-grants-2016_08
Patent number
US09408907B2

Reaction notes

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