Heterocyclic compounds and their use in preventing or treating bacterial infections
A compound and heterocyclic technology, applied in the field of β-lactamase inhibitors and/or antibacterial agents, preventing or treating bacterial infections, can solve the problem of low efficiency of bacterial strains
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0270] Example 1: (7-oxo-4-pyrazol-4-yl-1,6-diaza-bicyclo[3.2.1]oct-3-en-6-yl)sodium sulfate synthesis
[0271]
[0272] Step 1: Preparation of intermediate tert-butyl 4-bromo-3-hydroxy-3,6-dihydro-2H-pyridine-1-carboxylate (1b)
[0273] Under an inert atmosphere, in a 250 mL round bottom flask, tert-butyl 4-bromo-3-oxo-3,6-dihydro-2H-pyridine-1-carboxylate (1a, according to Tetrahedron Lett., 1994, 35, 3589-3592) (2.875g, 10.41mmol). The clear solution was cooled to 0° C. with an ice bath, followed by the addition of cerium(III) chloride heptahydrate (4.46 g, 11.97 mmol). Over 20 minutes, add NaBH in several portions 4(0.492 g, 13.01 mmol). The resulting suspension was stirred until complete conversion of the starting material. exist The reaction mixture was filtered on Celite, washing with MeOH (50 mL). The filtrate was diluted with EtOAc (250 mL), and cooled to 0 °C. Aqueous 0.1M hydrochloric acid was added to obtain pH 5-6. The aqueous layer was extracted...
Embodiment 2
[0304] Example 2: [4-(2-methylpyrazol-3-yl)-7-oxo-1,6-diazabicyclo[3.2.1]oct-3-en-6-yl] Synthesis of Sodium Sulfate
[0305]
[0306] Step 1: Intermediate 6-allyloxy-4-(2-methylpyrazol-3-yl)-1,6-diazabicyclo[3.2.1]oct-3- Preparation of en-7-one (2a)
[0307] In a Wheaton vial, 6-allyloxy-4-bromo-1,6-diazabicyclo[3.2.1]oct-3-en-7-one (1e) (30 mg, 0.116mmol), 1-methyl-1H-pyrazole-5-boronic acid pinacol ester (28.9mg, 0.139mmol) and anhydrous CsCO 3 (75.4 mg, 0.232 mmol) was dissolved in anhydrous THF (1.3 mL). The solution was degassed by bubbling argon for 10 min, and Pd(PPh 3 ) 4 (4.0 mg, 0.003 mmol). The reaction mixture was heated at 60°C for 90 minutes. Join H 2 O (1 mL), and the mixture was extracted with EtOAc (2 x 1 mL). use Na 2 SO 4 The organic layer was dried, filtered and concentrated under vacuum to give the crude material which was purified by preparative TLC (toluene / acetone: 8 / 2) to give the desired product 6-allyloxy-4-(2 -Methylpyrazol-3-yl...
Embodiment 3
[0320] Example 3: [4-(oxazol-5-yl)-7-oxo-1,6-diazabicyclo[3.2.1]oct-3-en-6-yl]sodium sulfate Synthesis
[0321]
[0322] Step 1: Intermediate 6-allyloxy-4-(oxazol-5-yl)-1,6-diazabicyclo[3.2.1]oct-3-ene-7- Preparation of ketone (3a)
[0323] Using the procedure described in Example 2 (step 1), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)oxazole (27.1 mg, 0.139 mmol) and after purification by preparative TLC (toluene / acetone: 8 / 2), the intermediate 6-allyloxy-4-bromo-1,6-diazabicyclo[3.2.1]octane- Conversion of 3-en-7-one (1e) (30 mg, 0.116 mmol) to 6-allyloxy-4-(oxazol-5-yl)-1,6-diazabicyclo[3.2.1]octane -3-en-7-one (3a) (2.4 mg, 0.010 mmol, 8.4%).
[0324] MS m / z ([M+H] + )248, ([M+Na] + )270.
[0325] 1 H NMR (300MHz, CDCl 3 ):δ(ppm)3.17(d, J=10.9Hz,1H),3.60(dd,J=10.9 / 3.0Hz,1H),3.84-4.00(m,2H),4.17-4.18(m,1H), 4.35-4.46 (m, 2H), 5.29-5.36 (m, 2H), 5.94-6.07 (m, 2H), 7.01 (s, 1H), 7.81 (s, 1H).
[0326] Step 2: Intermediate triphenyl-(propenyl)-quatern...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More