HCID 59506412, compound → HCID 178469730, compound

HRID 1798904Notes

Reaction equation

HRID 1798904 reaction equation
[CH2:1]([N:8]1[C:13]2[N:14]=[C:15]([S:20][CH3:21])[N:16]=[C:17]([NH:18][NH2:19])[C:12]=2[C:11](=O)[CH:10]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>Cl.O1CCOCC1>[CH2:1]([N:8]1[C:13]2[C:12]3[C:11](=[N:19][NH:18][C:17]=3[N:16]=[C:15]([S:20][CH3:21])[N:14]=2)[CH:10]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

3

Reactant 1

HCID 59506412HCID 59506412, compound

Product 1

HCID 178469730HCID 178469730, compoundYield 12.3%

Reagents, catalysts & solvents 1

HCID 204431481,4-Dioxane hydrochlorideSolvent

Procedure

Ethyl 8-benzyl-4-hydrazinyl-2-(methylthio)-5-oxo-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine-6-carboxylate (45 g) was taken in 4M dioxane-HCl (500 mL) and refluxed for 16 h. The reaction was concentrated under reduced pressure. Aq. NaHCO3 (250 mL) was added to the residue and the mixture was extracted with dichloromethane (200 mL×3). The combined organic layer was washed with water (500 mL), brine (500 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue which was purified by column chromatography (silica gel) using 0-10% tetrahydrofuran in dichloromethane as the eluent. The obtained product was further purified by crystallization from EtOAc to afford pure ethyl 5-benzyl-7-(methylthio)-1,3,4,5-tetrahydro-1,2,5,6,8-pentaazaacenaphthylene-3-carboxylate as a solid (5.2 g, 12.3% yield over 3 steps). LCMS: 370 (M+1)+; HPLC: 95.60% (254 nm); 1H NMR (DMSO-d6, 400 MHz) δ 13.15 (s, 1H); 7.38-7.30 (m, 5H); 4.92 (d, J=15.2 Hz, 1H); 4.67 (d, J=15.6 Hz, 1H); 4.34 (t, J=4.8 Hz, 1H); 4.06-3.96 (m, 2H); 3.88-3.79 (m, 2H); 2.5 (s, 3H); 1.08 (t, J=7.2 Hz, 3H).

Workup

  1. temperaturerefluxed for 16 h
  2. concentrationThe reaction was concentrated under reduced pressure
  3. additionAq. NaHCO3 (250 mL) was added to the residue
  4. extractionthe mixture was extracted with dichloromethane (200 mL×3)
  5. washThe combined organic layer was washed with water (500 mL), brine (500 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give a residue which
  10. customwas purified by column chromatography (silica gel)
  11. customThe obtained product was further purified by crystallization from EtOAc

Sources & evidence

ORD record
ord-7eeec01c35724549adfdd37c1858c08e
Source dataset
uspto-grants-2013_01
Patent number
US08343983B2

Reaction notes

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