2(1H)-Pyrimidinone, tetrahydro- → HCID 22346465, compound

HRID 897328Notes

Reaction equation

HRID 897328 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][NH:3][C:2]1=[O:7].Br[C:9]1[N:18]=[C:17]([C:19]([NH:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)=[O:20])[C:16]([OH:30])=[C:15]2[C:10]=1[CH:11]=[CH:12][CH:13]=[N:14]2>N1C=CC=CC=1>[F:29][C:26]1[CH:25]=[CH:24][C:23]([CH2:22][NH:21][C:19]([C:17]2[C:16]([OH:30])=[C:15]3[C:10]([CH:11]=[CH:12][CH:13]=[N:14]3)=[C:9]([N:1]3[CH2:6][CH2:5][CH2:4][NH:3][C:2]3=[O:7])[N:18]=2)=[O:20])=[CH:28][CH:27]=1

Participants

4

Reactant 2

HCID 746152(1H)-Pyrimidinone, tetrahydro-HCID 223464015-bromo-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide

Product 1

HCID 22346465HCID 22346465, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a mixture of tetrahydro-2-pyrimidone (0.040 g, 0.4 mmol), 5-bromo-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide (0.050 g, 0.13 mmol), and Cu2O (0.0095 g, 0.07 mmol) under an atmosphere of argon was added pyridine (1.0 mL) and the suspension was stirred at reflux for 16 hr. Cu2O (0.005 g, 0.04 mmol) was added and the reaction heated at 115 C for a further 16 hr. The reaction was allowed to cool to room temperature and the solvent evaporated in vacuo. The residue was treated with DMF (2 mL) and filtered to remove the solids. TFA (0.5 mL) was added to the filtrate which was purified by reverse phase HPLC. (Waters PrePak 500 cartridge C18, Gradient elution with Water:Acetonitrile 95:5 to 5:95 with 0.1% TFA at 75 mL/min over 45 mins). Lyophilization of the pure fractions afforded the title compound as an off white solid.

Workup

  1. temperatureat reflux for 16 hr
  2. temperaturethe reaction heated at 115 C for a further 16 hr
  3. customthe solvent evaporated in vacuo
  4. additionThe residue was treated with DMF (2 mL)
  5. filtrationfiltered
  6. customto remove the solids
  7. additionTFA (0.5 mL) was added to the filtrate which
  8. customwas purified by reverse phase HPLC
  9. wash(Waters PrePak 500 cartridge C18, Gradient elution with Water:Acetonitrile 95:5 to 5:95 with 0.1% TFA at 75 mL/min over 45 mins)

Sources & evidence

ORD record
ord-22ccf0318b734529ba6daafbf3043d8b
Source dataset
uspto-grants-2005_07
Patent number
US06921759B2

Reaction notes

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