7-(1-Acetyl-1,2,3,6-tetrahydro-pyridin-4-YL)-9-cyclopropyl-6-fluoro-9H-isothiazolo[5,4-B]quinoline-3,4-dione → 7-(1,2,3,6-Tetrahydro-pyridin-4-YL)-9-cyclopropyl-6-fluoro-9H-isothiazolo[5,4-B]quinoline-3,4-dione

HRID 1640958Notes

Reaction equation

HRID 1640958 reaction equation
C([N:4]1[CH2:9][CH:8]=[C:7]([C:10]2[CH:19]=[C:18]3[C:13]([C:14](=[O:27])[C:15]4[C:25](=[O:26])[NH:24][S:23][C:16]=4[N:17]3[CH:20]3[CH2:22][CH2:21]3)=[CH:12][C:11]=2[F:28])[CH2:6][CH2:5]1)(=O)C>Cl>[NH:4]1[CH2:5][CH:6]=[C:7]([C:10]2[CH:19]=[C:18]3[C:13]([C:14](=[O:27])[C:15]4[C:25](=[O:26])[NH:24][S:23][C:16]=4[N:17]3[CH:20]3[CH2:22][CH2:21]3)=[CH:12][C:11]=2[F:28])[CH2:8][CH2:9]1

Participants

3

Reactant 1

HCID 584268547-(1-Acetyl-1,2,3,6-tetrahydro-pyridin-4-YL)-9-cyclopropyl-6-fluoro-9H-isothiazolo[5,4-B]quinoline-3,4-dione

Product 1

HCID 115666097-(1,2,3,6-Tetrahydro-pyridin-4-YL)-9-cyclopropyl-6-fluoro-9H-isothiazolo[5,4-B]quinoline-3,4-dioneYield 98%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Conditions

Temperature
90 °C

Procedure

Compound 26 (11.1 mg, 0.028 mmol) is dissolved partially in an aqueous solution of hydrochloric acid (6 M, 3.0 mL) in air and heated at 90° C. to give an amber solution. After 22 h of heating, the solvent is removed under reduced pressure. The residue is dissolved in water (˜3 mL) and titrated to pH 7 with dilute sodium hydroxide. The precipitated solid is collected by filtration, washed with water (2×10 mL), and dried in vacuo to give 27 as a yellow solid (98% purity by HPLC). mp >241-242° C. dec. 1H NMR (DMSO-d6/acetic acid-d4 (5:1 v/v)): δ 1.19 (m, 2H, c-Pr CH2), 1.29 (m, 2H, c-Pr CH2), 2.72 (m, 2H, NCH2CH2), 3.33 (m, 2H, NCH2CH2), 3.54 (m, 1H, c-Pr CH), 3.80 (m, 2H, NCH2CH), 6.21 (m, 1H, NCH2CH), 7.87 (br, 1H, aromatic), 7.91 (br, 1H, aromatic). 19F{1H} NMR (DMSO-d6/acetic acid-d4 (5:1 v/v)): δ −121.4 (s). LCMS m/z calcd for C18H16FN3O2S ([M]+) 357. Found 358 ([M+H]+). HRMS m/z calcd for C18H16FN3NaO2S ([M+Na]+) 380.0845. Found 380.0847.

Workup

  1. customto give an amber solution
  2. temperatureAfter 22 h of heating
  3. customthe solvent is removed under reduced pressure
  4. dissolutionThe residue is dissolved in water (˜3 mL)
  5. filtrationThe precipitated solid is collected by filtration
  6. washwashed with water (2×10 mL)
  7. customdried in vacuo

Sources & evidence

ORD record
ord-7bdc4d93c8174b118b8ba867d38760b8
Source dataset
uspto-grants-2012_02
Patent number
US08114888B2

Reaction notes

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