Potassium Carbonate → 7-Fluorobenzo[f][1,7]naphthyridin-5-amine

HRID 1479480Notes

Reaction equation

HRID 1479480 reaction equation
C(OC([NH:8][C:9]1[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=1B(O)O)=O)(C)(C)C.Br[C:20]1[C:21]([C:26]#[N:27])=[N:22][CH:23]=[CH:24][CH:25]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.CO.ClCCl.O>[F:15][C:14]1[C:9]2[C:10](=[C:20]3[C:21](=[C:26]([NH2:27])[N:8]=2)[N:22]=[CH:23][CH:24]=[CH:25]3)[CH:11]=[CH:12][CH:13]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 8176943-Bromopyridine-2-carbonitrileHCID 66874632HCID 66874632, compound

Product 1

HCID 582135407-Fluorobenzo[f][1,7]naphthyridin-5-amine

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 2-(tert-butoxycarbonylamino)-3-fluorophenylboronic acid (from step 2) (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 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. After workup, the crude product was suspended in hot toluene, centrifuged (2500 rpm, 5 min), and the supernatant was removed. The suspension, centrifugation, and removal of supernatant steps were repeated with hot ethyl acetate, ether, and hexane to give a pure solid. 1H NMR (acetone d-6): δ 9.04 (d, 1H), 8.96 (d, 1H), 8.27 (d, 1H), 7.86-7.90 (dd, 1H), 7.28-7.34 (m, 2H), 6.9 (br, 2H). LRMS [M+H]=214.1

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. customcentrifuged (2500 rpm, 5 min), and the supernatant was removed
  8. customThe suspension, centrifugation, and removal of supernatant steps
  9. customto give a pure solid

Sources & evidence

ORD record
ord-66adf6d26a554b6eb4741c810219f250
Source dataset
uspto-grants-2016_08
Patent number
US09408907B2

Reaction notes

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