Pyridine → HCID 89606157, compound

HRID 1430541Notes

Reaction equation

HRID 1430541 reaction equation
[NH2:1][C:2]1[C:3]([F:23])=[CH:4][C:5]([Cl:22])=[C:6]([C:8]2[C:9](=[O:21])[N:10]([CH2:19][CH3:20])[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13]([Cl:18])[CH:12]=3)[CH:7]=1.N1C=CC=CC=1.[C:30]1([N:36]=[C:37]=[O:38])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C([O-])(O)=O.[Na+]>C1COCC1.O=S(Cl)Cl.O.CCOC(C)=O>[Cl:22][C:5]1[C:6]([C:8]2[C:9](=[O:21])[N:10]([CH2:19][CH3:20])[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13]([Cl:18])[CH:12]=3)=[CH:7][C:2]([NH:1][C:37]([NH:36][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[O:38])=[C:3]([F:23])[CH:4]=1

Participants

9

Reactant 4

HCID 1049PyridineHCID 7672Phenyl isocyanateHCID 516892Sodium BicarbonateHCID 877715763-(5-Amino-2-chloro-4-fluorophenyl)-7-chloro-1-ethyl-1,6-naphthyridin-2(1h)-one

Product 1

HCID 89606157HCID 89606157, compoundYield 54.7%

Reagents, catalysts & solvents 4

HCID 24386Thionyl ChlorideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of Example A3 (500 mg, 1.420 mmol) and pyridine (449 mg, 5.68 mmol) in THF (20 mL) was treated with phenyl isocyanate (186 mg, 1.562 mmol) and stirred at RT for 20 h. The mixture was accidentally treated with a few drops of SOCl2; EtOAc, water and satd. NaHCO3 were added and the mixture stirred at RT for 2 h. The resulting solid was collected via filtration and dried. The layers of the filtrate were separated, the organic layer washed with brine, dried over Na2SO4 and concentrated to dryness. The material was treated with EtOAc, sonicated for 2 minutes, collected via filtration and combined with the above-isolated solid to afford 1-(4-chloro-5-(7-chloro-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-phenylurea (366 mg, 54% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.10 (s, 1H), 8.79 (s, 1H), 8.74 (s, 1H), 8.24 (d, J=8.6 Hz, 1H), 8.09 (s, 1H), 7.75 (s, 1H), 7.60 (d, J=11.0 Hz, 1H), 7.41 (d, J=8.0 Hz, 2H), 7.26 (t, J=7.8 Hz, 2H), 6.97 (t, J=7.3 Hz, 1H), 4.27 (q, J=7.1 Hz, 2H), 1.20 (t, J=7.0 Hz, 3H).

Workup

  1. stirringthe mixture stirred at RT for 2 h
  2. filtrationThe resulting solid was collected via filtration
  3. customdried
  4. customThe layers of the filtrate were separated
  5. washthe organic layer washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness
  8. additionThe material was treated with EtOAc
  9. customsonicated for 2 minutes
  10. filtrationcollected via filtration

Sources & evidence

ORD record
ord-92ac2df7612347c1b1c596002af17531
Source dataset
uspto-grants-2015_01
Patent number
US08940756B2

Reaction notes

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