Acetonitrile → HCID 56959107, compound

HRID 1854858Notes

Reaction equation

HRID 1854858 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].[NH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1.C([O-])(O)=O.[Na+].C(#[N:34])C>C(OCC)(=O)C>[NH2:34][C@H:23]1[CH2:24][CH2:25][CH2:26][N:21]([C:2]2[CH:3]=[CH:4][N:5]3[C:10]([C:11]=2[CH3:12])=[C:9]([CH:13]2[CH2:14][CH2:15]2)[CH:8]=[C:7]([C:16]([OH:18])=[O:17])[C:6]3=[O:20])[CH2:22]1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 8082PiperidineHCID 516892Sodium BicarbonateHCID 86696543Methyl 8-chloro-1-cyclopropyl-9-methyl-4-oxo-quinolizine-3-carboxylate

Product 1

HCID 56959107HCID 56959107, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of methyl 8-chloro-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylate (300 mg, 1 mmol), 3-S—N-(tert-butoxycarbonyl)-amino)-piperidine (413 mg, 2 mmol) and NaHCO3 (390 mg, 14.64 mmol) in ACN (13 mL) was heated in a microwave at 120° C. for 20 min, and twice at 130° C. for 30 min. 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 (1.4 mL) and heated in a microwave at 100° C. for 10 min and at 120° C. for 10 min. The mixture was evaporated and the residue purified by preparative HPLC. The title compound EXAMPLE 35 was obtained after lyophilization (65 mg, 19%). High-Res MS: calculated m/z 342.1812 (M+H)+. found m/z 342.1787 (M+H)+.

Workup

  1. washwashed with water (30 mL)
  2. extractionAfter extraction of the aqueous phase with ethyl acetate (2×30 mL)
  3. washthe organic phases were combined washed with brine
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltrated
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in TFA (1 mL)
  8. customto evaporation of the solvent
  9. dissolutionThe residue was dissolved in THF (1 mL)
  10. temperaturean aqueous 4M NaOH solution (1.4 mL) and heated in a microwave at 100° C. for 10 min and at 120° C. for 10 min
  11. customThe mixture was evaporated
  12. customthe residue purified by preparative HPLC

Sources & evidence

ORD record
ord-a93fa091bfba4fadad8528a1d086acd1
Source dataset
uspto-grants-2015_02
Patent number
US08962842B2

Reaction notes

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