4H-Quinolizine-3-carboxylicacid, 8-[(3S)-3-amino-1-pyrrolidinyl]-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-,hydrochloride (1:1) → HCID 479584, compound

HRID 1080215Notes

Reaction equation

HRID 1080215 reaction equation
Cl.[NH2:2][C@H:3]1[CH2:7][CH2:6][N:5]([C:8]2[C:9]([F:26])=[CH:10][N:11]3[C:16]([C:17]=2[CH3:18])=[C:15]([CH:19]2[CH2:21][CH2:20]2)[CH:14]=[C:13]([C:22]([OH:24])=[O:23])[C:12]3=[O:25])[CH2:4]1.C([O-])(=O)C.[Na+].CO[C:34]1(OC)[CH2:38][CH2:37][CH2:36]O1>C(OCC)(=O)C>[CH:19]1([C:15]2[CH:14]=[C:13]([C:22]([OH:24])=[O:23])[C:12](=[O:25])[N:11]3[C:16]=2[C:17]([CH3:18])=[C:8]([N:5]2[CH2:6][CH2:7][C@H:3]([N:2]4[CH:34]=[CH:38][CH:37]=[CH:36]4)[CH2:4]2)[C:9]([F:26])=[CH:10]3)[CH2:20][CH2:21]1

Participants

5

Reactant 3

HCID 1780734H-Quinolizine-3-carboxylicacid, 8-[(3S)-3-amino-1-pyrrolidinyl]-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-,hydrochloride (1:1)HCID 517045Sodium AcetateHCID 11788317dimethoxytetrahydrofurane

Product 1

HCID 479584HCID 479584, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 25 mg 8-(3(S)-aminopyrrolidinyl)-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylic acid hydrochloride (from Example 257) and 40 mg of sodium acetate in 0.7 mL of ethyl acetate was heated to 100° C. To this solution was added 0.009 mL of dimethoxytetrahydrofuran dropwise, and the reaction was stirred at 110° C. for 5 min, then quenched by addition of water. The mixture was extracted twice with methylene chloride, and the extract was washed with water, dried over MgSO4 and concentrated. The residue was purified by preparative TLC, eluting with 100:10 chloroform:methanol, to give 13.6 mg of the title product as a yellow solid after removal of the solvent. MS 395 (M-Cl)+. 1H NMR (CDCl3) δ: 0.67 (m, 2H), 1.00 (m, 2H), 2.20 (m, 1H), 2.46 (m, 1H), 2.56 (m, 1H), 2.66 (s, 3H), 3.89 (m, 1H), 3.99 (m, 2H0, 4.15 (m, 1H), 4.86 (m, 1H), 6.23 (t, 2H, J=2 Hz), 6.79 (t, 2H, J=2 hz), 8.32 (s, 1H), 9.15 (d, 1H, J=10 Hz), 13.83 (br, 1H).

Workup

  1. customquenched by addition of water
  2. extractionThe mixture was extracted twice with methylene chloride
  3. washthe extract was washed with water
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by preparative TLC
  7. washeluting with 100:10 chloroform

Sources & evidence

ORD record
ord-3b78738826ca494097a79810660cfe08
Source dataset
uspto-grants-1996_12
Patent number
US05580872

Reaction notes

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