Isopropylamine → 2-[(3-chlorophenyl)methyl]-9-hydroxy-N-isopropyl-1,8-dioxo-pyrido[1,2-a]pyrazine-7-carboxamide

HRID 1349493Notes

Reaction equation

HRID 1349493 reaction equation
C([O:8][C:9]1[C:10](=[O:35])[C:11]([C:32]([OH:34])=O)=[CH:12][N:13]([CH2:26][CH:27](OC)OC)[C:14]=1[C:15](=[O:25])[NH:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[CH:19]=1)C1C=CC=CC=1.S(Cl)(Cl)=O.[CH:40]([NH2:43])([CH3:42])[CH3:41].S([O-])(O)=O.[K+]>O1CCCC1.C(N(CC)CC)C>[CH:40]([NH:43][C:32]([C:11]1[C:10](=[O:35])[C:9]([OH:8])=[C:14]2[C:15](=[O:25])[N:16]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([Cl:24])[CH:19]=3)[CH:27]=[CH:26][N:13]2[CH:12]=1)=[O:34])([CH3:42])[CH3:41]

Participants

7

Reactant 4

HCID 6363IsopropylamineHCID 24386Thionyl ChlorideHCID 230776405-Benzyloxy-6-(3-chlorobenzylcarbamoyl)-1-(2,2-dimethoxyethyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acidHCID 23663620Potassium Bisulfite

Product 1

HCID 547079162-[(3-chlorophenyl)methyl]-9-hydroxy-N-isopropyl-1,8-dioxo-pyrido[1,2-a]pyrazine-7-carboxamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 5-benzyloxy-6-(3-chlorobenzylcarbamoyl)-1-(2,2-dimethoxyethyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acid (25.4 mg) obtained in Example 161, Step 4 in tetrahydrofuran (0.3 ml) were successively added triethylamine (0.021 ml) and thionyl chloride (0.0056 ml) at 0° C. with stirring. After stirring at room temperature for 10 min, the mixture was ice-cooled again and isopropylamine (0.0086 ml) was added. After stirring at room temperature for 30 min, 5% aqueous potassium hydrogen sulfite solution was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with brine, dried and concentrated. Trifluoroacetic acid was added to the obtained residue and the mixture was stirred at 70° C. for 5.5, hr. Trifluoroacetic acid was evaporated, toluene was added and the mixture was concentrated, which operations were performed twice. Crystallization from ethyl acetate (2 ml) gave 2-(3-chlorobenzyl)-9-hydroxy-1,8-dioxo-1,8-dihydro-2H-pyrido[1,2-a]pyrazine-7-carboxylic acid isopropylamide (13.6 mg)

Workup

  1. customat 0° C.
  2. stirringAfter stirring at room temperature for 10 min
  3. temperaturecooled again
  4. stirringAfter stirring at room temperature for 30 min
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe ethyl acetate layer was washed with brine
  7. customdried
  8. concentrationconcentrated
  9. additionTrifluoroacetic acid was added to the obtained residue
  10. stirringthe mixture was stirred at 70° C. for 5.5, hr
  11. customTrifluoroacetic acid was evaporated
  12. additiontoluene was added
  13. concentrationthe mixture was concentrated
  14. customCrystallization from ethyl acetate (2 ml)

Sources & evidence

ORD record
ord-f6caa1d9ad344b7b8d0b9157f4dfa591
Source dataset
uspto-grants-2007_05
Patent number
US07211572B2

Reaction notes

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