Dimethylformamide → HCID 56959109, compound

HRID 1854857Notes

Reaction equation

HRID 1854857 reaction equation
Cl[C:2]1[CH:3]=[CH:4][N:5]2[C:10]([C:11]=1[CH3:12])=[C:9]([CH:13]1[CH2:15][CH2:14]1)[CH:8]=[C:7]([C:16]([O:18]C)=[O:17])[C:6]2=[O:20].C(OC([N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)=O)(C)(C)C.C([O-])(O)=O.[Na+].CN(C=O)C>C(#N)C.C(OCC)(=O)C>[CH:13]1([C:9]2[CH:8]=[C:7]([C:16]([OH:18])=[O:17])[C:6](=[O:20])[N:5]3[C:10]=2[C:11]([CH3:12])=[C:2]([N:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)[CH:3]=[CH:4]3)[CH2:14][CH2:15]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 143452tert-Butyl piperazine-1-carboxylateHCID 516892Sodium BicarbonateHCID 86696543Methyl 8-chloro-1-cyclopropyl-9-methyl-4-oxo-quinolizine-3-carboxylate

Product 1

HCID 56959109HCID 56959109, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of methyl 8-chloro-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylate (200 mg, 0.69 mmol), N-(tert-butoxycarbonyl)-piperazine (256 mg, 1.38 mmol) and NaHCO3 (259 mg, 14.64 mmol) in ACN (8.6 mL) was heated in a microwave at 120° C. for 20 min. DMF (2 mL) was added to the mixture and the reaction was heated in a microwave at 120° C. for 20 min. Then the reaction was heated in a microwave at 130° C. for 30 min twice. The reaction mixture was diluted with ethyl acetate (30 mL), and washed with water (30 mL). After extraction of the aqueous phase with ethyl acetate (2×30 mL), the organic phases were combined washed with brine, dried with magnesium sulfate, filtrated, and concentrated. The residue was dissolved in TFA (1 mL) and agitated for 1 hour prior to evaporation of the solvent. The residue was dissolved in THF (1 mL) and an aqueous 4M NaOH solution (0.79 mL) and heated in a microwave at 120° C. for 10 min. More aqueous 4M NaOH solution (0.5 mL) was added and the reaction was heated in a microwave at 120° C. for 10 min. The mixture was evaporated and the residue purified by preparative HPLC. The title compound EXAMPLE 34 was obtained after lyophilization (28 mg, 12.5%). High-Res MS: calculated 328.1656 (M+H)+. found 328.1642 (M+H)+.

Workup

  1. temperaturethe reaction was heated in a microwave at 120° C. for 20 min
  2. temperatureThen the reaction was heated in a microwave at 130° C. for 30 min twice
  3. washwashed with water (30 mL)
  4. extractionAfter extraction of the aqueous phase with ethyl acetate (2×30 mL)
  5. washthe organic phases were combined washed with brine
  6. dry with materialdried with magnesium sulfate
  7. filtrationfiltrated
  8. concentrationconcentrated
  9. dissolutionThe residue was dissolved in TFA (1 mL)
  10. customto evaporation of the solvent
  11. dissolutionThe residue was dissolved in THF (1 mL)
  12. temperaturean aqueous 4M NaOH solution (0.79 mL) and heated in a microwave at 120° C. for 10 min
  13. additionMore aqueous 4M NaOH solution (0.5 mL) was added
  14. temperaturethe reaction was heated in a microwave at 120° C. for 10 min
  15. customThe mixture was evaporated
  16. customthe residue purified by preparative HPLC

Sources & evidence

ORD record
ord-a494043f1453405397dbee601ff88895
Source dataset
uspto-grants-2015_02
Patent number
US08962842B2

Reaction notes

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