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[ CAS No. 179337-57-6 ] {[proInfo.proName]}

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Chemical Structure| 179337-57-6
Chemical Structure| 179337-57-6
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Product Details of [ 179337-57-6 ]

CAS No. :179337-57-6 MDL No. :MFCD18072489
Formula : C6H11ClN2S2 Boiling Point : -
Linear Structure Formula :- InChI Key :WLQPQHGYHHHITD-UHFFFAOYSA-N
M.W : 210.75 Pubchem ID :11974883
Synonyms :

Calculated chemistry of [ 179337-57-6 ]

Physicochemical Properties

Num. heavy atoms : 11
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.83
Num. rotatable bonds : 1
Num. H-bond acceptors : 1.0
Num. H-bond donors : 0.0
Molar Refractivity : 63.03
TPSA : 79.7 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.68 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.0
Log Po/w (XLOGP3) : 1.28
Log Po/w (WLOGP) : 0.74
Log Po/w (MLOGP) : 1.23
Log Po/w (SILICOS-IT) : 2.04
Consensus Log Po/w : 1.06

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -1.89
Solubility : 2.73 mg/ml ; 0.013 mol/l
Class : Very soluble
Log S (Ali) : -2.55
Solubility : 0.59 mg/ml ; 0.0028 mol/l
Class : Soluble
Log S (SILICOS-IT) : -0.9
Solubility : 26.7 mg/ml ; 0.127 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 3.65

Safety of [ 179337-57-6 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 179337-57-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 179337-57-6 ]

[ 179337-57-6 ] Synthesis Path-Downstream   1~43

  • 1
  • [ 19975-56-5 ]
  • 3-mercaptoazetidine hydrochloride [ No CAS ]
  • 1-(4,5-dihydro-1,3-thiazol-2-yl)-3-mercaptoazetidine hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
(2) 21.3 g of 3-mercaptoazetidine hydrochloride and 0.1 g of potassium iodide prepared in the step (1) are added to 60 ml of water, and then a saturated potassium iodate solution is added at 30 C, and the reaction is terminated by thin layer chromatography. After that, add 60 ml of dichloromethane and stir for 10 minutes, separate the liquid, take the water layer, adjust the pH value with a 30 wt% sodium hydroxide solution, filter, and dry to obtain a solid.(3) The solid (2) obtained in the step2-methylthiothiazolineThe coupling reaction occurs to obtain a disulfide; (4) 11 mmol of the disulfide obtained in the step (3) and 23 mmol of triphenylphosphine, 4.7 g of 36% hydrochloric acid and 45 ml of ethanol are mixed and heated to 30 C, and the reaction is kept until the reaction is carried out. The reaction was monitored by TLC until the conversion of the starting material was complete, and the temperature of the reaction solution was raised to 60 C.After concentration, the mixture was concentrated to dryness. After dissolved in 20 ml of ethanol, the temperature was lowered to 0 to 5 C, 100 ml of isopropyl ether was slowly added dropwise, and the mixture was kept for 1 hour, filtered, and dried to obtain compound 3.
  • 2
  • [ CAS Unavailable ]
  • [ 179337-57-6 ]
YieldReaction ConditionsOperation in experiment
80% With sodium methylate; phenylmethanethiol In methanol at 20℃; for 1h;
  • 3
  • [ CAS Unavailable ]
  • [ 384330-54-5 ]
  • [ 179337-57-6 ]
YieldReaction ConditionsOperation in experiment
1: 14% 2: 76% With hydrogenchloride In water at 60℃;
  • 4
  • [ 161715-28-2 ]
  • [ 179337-57-6 ]
YieldReaction ConditionsOperation in experiment
87% Stage #1: 3-acetylthio-1-(1,3-thiazolin-2-yl)azetidine With potassium hydroxide In methanol; isopropyl alcohol at 5℃; for 0.166667h; Stage #2: With hydrogenchloride In methanol; isopropyl alcohol at 5℃; for 15h;
73.2 g Stage #1: 3-acetylthio-1-(1,3-thiazolin-2-yl)azetidine With sodium methylate In methanol at 5℃; for 1h; Stage #2: With hydrogenchloride In dichloromethane at 10℃; for 0.5h; Synthesis of Compound I The reaction flask was charged with 95.4 g of the crude compound X and 500 ml of methanol obtained in the previous step,After cooling to 5 ° C, 27 g of sodium methoxide (0.50 mol) was added and the reaction was stirred at this temperature for 1 hour until the starting material disappeared,The reaction solution was concentrated to dryness and the residue was dissolved in 600 ml of methylene chloride. The temperature was less than 10 ° C,The dry hydrogen chloride gas was then passed to pH = 1 and stirring was continued at that temperature for 30 minutes,The filter cake was washed with 200 ml of dichloromethane, dried,And finally recrystallized from 150 ml of methanol and 450 ml of acetone to give 73.2 g of a white solid,Ie Compound I, HPLC content: 99.47% (area normalized).
  • 5
  • [ CAS Unavailable ]
  • [ 108-98-5 ]
  • [ 914615-58-0 ]
  • [ 179337-57-6 ]
YieldReaction ConditionsOperation in experiment
61% at 20℃; for 24h;
  • 6
  • [ CAS Unavailable ]
  • [ 100-53-8 ]
  • [ 914615-59-1 ]
  • [ 179337-57-6 ]
YieldReaction ConditionsOperation in experiment
8% at 20℃; for 24h;
  • 7
  • [ CAS Unavailable ]
  • [ 60-24-2 ]
  • [ 914615-57-9 ]
  • [ 179337-57-6 ]
YieldReaction ConditionsOperation in experiment
56% at 20℃; for 24h;
  • 8
  • [ 90776-59-3 ]
  • [ 179337-57-6 ]
  • [ 161715-20-4 ]
YieldReaction ConditionsOperation in experiment
94% With N-ethyl-N,N-diisopropylamine; acetonitrile at -20℃; for 2h;
88.5% With N-ethyl-N,N-diisopropylamine at -20℃; for 3.5h; 2 Preparation of intermediate I The 1-(4,5-Dihydro-2-thiazolyl)-3-azetidinethiol hydrochloride 274.0g(1.3mol) and 1β-Methyl vinyl phosphate 594.5g(1mol)added to 1783ml of Diisopropylethylamine and stirred the reaction at -20°C for 3.5h. After the end of the reaction, 900 ml of pure water was added and the temperature was raised to 0 ° C in 30 minutes. The filter cake was washed with 297 ml of acetonitrile water (V acetonitrile: Vwater = 2: 3) and dried to give I 458.4 g of intermediate. the calculated yield was 88.5% and the purity was 99.2%.
With N-ethyl-N,N-diisopropylamine In acetonitrile
  • 9
  • [ CAS Unavailable ]
  • [ 179337-57-6 ]
  • [ 384330-54-5 ]
YieldReaction ConditionsOperation in experiment
73% With sodium methylate
  • 10
  • [ CAS Unavailable ]
  • [ CAS Unavailable ]
  • [ 914615-56-8 ]
  • [ 179337-57-6 ]
YieldReaction ConditionsOperation in experiment
19% at 20℃; for 24h;
  • 11
  • [ 179337-62-3 ]
  • [ 179337-57-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: 88 percent / potassium thioacetate / dimethylformamide / 5.5 h / 100 °C 2.1: KOH / propan-2-ol; methanol / 0.17 h / 5 °C 2.2: 87 percent / HCl / propan-2-ol; methanol / 15 h / 5 °C
  • 12
  • [ 161715-27-1 ]
  • [ 179337-57-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: 93 percent / DMAP; Et3N / tetrahydrofuran / 0.5 h / 5 °C 2.1: 88 percent / potassium thioacetate / dimethylformamide / 5.5 h / 100 °C 3.1: KOH / propan-2-ol; methanol / 0.17 h / 5 °C 3.2: 87 percent / HCl / propan-2-ol; methanol / 15 h / 5 °C
  • 13
  • [ 179337-57-6 ]
  • [ 161715-21-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 94 percent / diisopropyl ethylamine; MeCN / 2 h / -20 °C 2: 82 percent / sodium hydrogen carbonate / Pd-C / butan-1-ol; H2O / 1.5 h / 20 °C / 3000.24 Torr
Multi-step reaction with 2 steps 1.1: acetonitrile / 0.17 h / 20 °C 1.2: 10 h / -20 °C 2.1: hydrogen; sodium hydrogencarbonate; palladium 10% on activated carbon / butan-1-ol; water / 7 h / 20 °C / 3000.3 - 3750.38 Torr
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / 3.5 h / -20 °C 2: 0.5% Pd/C; sodium hydrogencarbonate; hydrogen / butan-1-ol; water / 3 h / 25 - 30 °C / 7500.75 Torr
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / acetonitrile 2: hydrogen; water; palladium on activated charcoal / butan-1-ol

  • 14
  • [ 179337-57-6 ]
  • [ 909779-82-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 94 percent / diisopropyl ethylamine; MeCN / 2 h / -20 °C 2: 82 percent / sodium hydrogen carbonate / Pd-C / butan-1-ol; H2O / 1.5 h / 20 °C / 3000.24 Torr 3: 54 percent / benzyltriethylammonium chloride; diisopropylethylamine / dimethylformamide / 4 h / 45 °C
  • 15
  • [ 179337-57-6 ]
  • [ 909779-83-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 94 percent / diisopropyl ethylamine; MeCN / 2 h / -20 °C 2: 82 percent / sodium hydrogen carbonate / Pd-C / butan-1-ol; H2O / 1.5 h / 20 °C / 3000.24 Torr 3: 84 percent / benzyltriethylammonium chloride; diisopropylethylamine / dimethylformamide / 4 h / 45 °C
  • 16
  • [ 179337-57-6 ]
  • [ 909779-84-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 94 percent / diisopropyl ethylamine; MeCN / 2 h / -20 °C 2: 82 percent / sodium hydrogen carbonate / Pd-C / butan-1-ol; H2O / 1.5 h / 20 °C / 3000.24 Torr 3: 84 percent / benzyltriethylammonium chloride; diisopropylethylamine / dimethylformamide / 4 h / 45 °C
  • 17
  • [ 179337-57-6 ]
  • [ 909779-85-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 94 percent / diisopropyl ethylamine; MeCN / 2 h / -20 °C 2: 82 percent / sodium hydrogen carbonate / Pd-C / butan-1-ol; H2O / 1.5 h / 20 °C / 3000.24 Torr 3: 81 percent / benzyltriethylammonium chloride; diisopropylethylamine / dimethylformamide / 4 h / 45 °C
  • 18
  • [ 179337-57-6 ]
  • [ 189383-32-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 94 percent / diisopropyl ethylamine; MeCN / 2 h / -20 °C 2: 82 percent / sodium hydrogen carbonate / Pd-C / butan-1-ol; H2O / 1.5 h / 20 °C / 3000.24 Torr 3: 71 percent / benzyltriethylammonium chloride; diisopropylethylamine / dimethylformamide / 4 h / 45 °C
  • 19
  • [ 179337-57-6 ]
  • [ 192638-15-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 94 percent / diisopropyl ethylamine; MeCN / 2 h / -20 °C 2: 82 percent / sodium hydrogen carbonate / Pd-C / butan-1-ol; H2O / 1.5 h / 20 °C / 3000.24 Torr 3: 80 percent / benzyltriethylammonium chloride; diisopropylethylamine / dimethylformamide / 4 h / 45 °C
  • 20
  • [ 179337-57-6 ]
  • [ 190774-46-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 94 percent / diisopropyl ethylamine; MeCN / 2 h / -20 °C 2: 82 percent / sodium hydrogen carbonate / Pd-C / butan-1-ol; H2O / 1.5 h / 20 °C / 3000.24 Torr 3: 82 percent / benzyltriethylammonium chloride; diisopropylethylamine / dimethylformamide / 4 h / 45 °C
  • 21
  • [ 179337-57-6 ]
  • [ 192571-04-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 94 percent / diisopropyl ethylamine; MeCN / 2 h / -20 °C 2: 82 percent / sodium hydrogen carbonate / Pd-C / butan-1-ol; H2O / 1.5 h / 20 °C / 3000.24 Torr 3: 88 percent / benzyltriethylammonium chloride; diisopropylethylamine / dimethylformamide / 4 h / 45 °C
  • 22
  • [ 179337-57-6 ]
  • [ 192571-03-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 94 percent / diisopropyl ethylamine; MeCN / 2 h / -20 °C 2: 82 percent / sodium hydrogen carbonate / Pd-C / butan-1-ol; H2O / 1.5 h / 20 °C / 3000.24 Torr 3: 76 percent / benzyltriethylammonium chloride; diisopropylethylamine / dimethylformamide / 4 h / 45 °C
  • 23
  • [ 179337-57-6 ]
  • [ 161715-24-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 94 percent / diisopropyl ethylamine; MeCN / 2 h / -20 °C 2: 82 percent / sodium hydrogen carbonate / Pd-C / butan-1-ol; H2O / 1.5 h / 20 °C / 3000.24 Torr 3: 78 percent / benzyltriethylammonium chloride; diisopropylethylamine / dimethylformamide / 4 h / 45 °C
Multi-step reaction with 3 steps 1.1: acetonitrile / 0.17 h / 20 °C 1.2: 10 h / -20 °C 2.1: hydrogen; sodium hydrogencarbonate; palladium 10% on activated carbon / butan-1-ol; water / 7 h / 20 °C / 3000.3 - 3750.38 Torr 3.1: potassium iodide / N,N-dimethyl-formamide / 3 h / 60 °C 3.2: 8 h / 0 °C
Multi-step reaction with 4 steps 1.1: N-ethyl-N,N-diisopropylamine / 3.5 h / -20 °C 2.1: 0.5% Pd/C; sodium hydrogencarbonate; hydrogen / butan-1-ol; water / 3 h / 25 - 30 °C / 7500.75 Torr 3.1: N-benzyl-N,N,N-triethylammonium chloride; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 35 °C 3.2: 7 - 8 °C 4.1: sodium hydrogencarbonate / water; ethyl acetate / 2.5 h
Multi-step reaction with 3 steps 1.1: N-ethyl-N,N-diisopropylamine / acetonitrile 2.1: hydrogen; water; palladium on activated charcoal / butan-1-ol 3.1: N-benzyl-N,N,N-triethylammonium chloride; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 25 °C / Large scale 3.2: 5 h / 45 °C / Large scale

  • 24
  • [ 682747-73-5 ]
  • [ 179337-57-6 ]
  • [ 161715-24-8 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In acetonitrile at -10℃; for 3h; 2 Example 2: Production of pivaloyloxymethyl (1R, 5S, 6S)-2-[1-(1,3-thiazolin-2-yl)azet idin-3-yl]thio-6-[(1R)-1-hydroxyethyl]-1-methyl-carbapen-2-em-3-carboxylate [] In 1 ml of acetonitrile, was dissolved 0.32 g of an oily residue containing (4R, 5R, 6S) -6-[(1R) -1-hydroxyethyl]-3-diphenylphosphorylox y-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxyl ic acid pivaloyloxymethyl ester synthesized and purified in the same manner as in Reference Example 3. To the resulting solution, was added 0.07 g (0.33 mmol) of a compound represented by formula (18): [] and was dropwise added 0.09 g (0.70 mmol) of diisopropylethylamine at -10°C, followed by stirring the mixture for 3 hours at the same temperature. After the completion of the reaction, 20 ml of ethyl acetate and 20 ml of water was added to the reaction mixture. To the resulting solution, was added aqueous citric acid solution to extract the target compound into the water phase. It was extracted again into the ethyl acetate phase by adding 20 ml of ethyl acetate and potassium bicarbonate. The resulting solution was dried over sodium sulfate, and then the solvent was removed by evaporation from the solution. The production of the title compound was confirmed by NMR analysis.
With N-ethyl-N,N-diisopropylamine In acetonitrile at -10℃; for 3h; 1 (Reference Example 1) Production of pivaloyloxymethyl (1R,5S,6S)-2-[1-(1,3-thiazolin-2-yl)azetidin-3-yl]thio-6-[(1R)-1-hydroxyethyl]-1-methyl-carbapen-2-em-3-carboxylate; [] A solution was prepared by dissolving 0.32 g of an oily residue containing (4R,5R,6S),-6-[(1R)-1-hydroxyethyl]-3-diphenylphosphoryloxy-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid pivaloyloxymethyl ester, which was synthesized as in Example 5 and purified, in 1 ml of acetonitrile, and 0.07 g (0.33 mmol) of a compound represented by formula (18): [] was added thereto. Subsequently, 0.09 g (0.70 mmol) of diisopropylethylamine was added dropwise thereto at -10°C, and stirring was performed at the same temperature for 3 hours. After the reaction was completed, 20 ml of ethyl acetate and 20 ml of water were added to the reaction solution, and extraction into an aqueous layer was carried out by adding aqueous citric acid, and then extraction into an ethyl acetate layer was carried out by adding 20 ml of ethyl acetate and potassium bicarbonate. The extraction solution was dried over sodium sulfate, and then the solvent was removed by distillation. NMR analysis confirmed the formation of the target compound. NMR δ (CDCl3) : 1.23 (9H, s), 1.23 (3H, d, J = 7.1), 1.34 (3H, d, J = 6.4 Hz), 3.13 - 3.21 (1H, m), 3.23 (1H, dd, J = 2.7, 6.8 Hz), 3.37 (2H, t, J = 7.6 Hz), 3.94 - 4.03 (4H, m), 4.10 - 4.26 (3H, m), 4.36 - 4.42 (2H, m), 5.84 (1H, d, J = 5.5 Hz), 5.97 (1H, d, J = 5.5 Hz)
With N-ethyl-N,N-diisopropylamine In acetonitrile Tebipenem pivoxil hydrobromide (TBPM-PI-HBr, SPR-994)can be obtained by several main ways: 2) Coupling of malonic acid monobenzyl ester (XVII) withiodomethyl pivalate (XVI) in the presence of DIEA in acetonitrile,followed by debenzylation with H2 over Pd/C in EtOAcgives malonic acid monopivaloyloxymethyl ester (XVIII),which is treated with MgBr2·Et2O or MgCl2 in THF, followedby coupling with azetidine derivative (XIX) [obtained bythe reaction of (3S,4S)-3-[(R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-[(R)-1-carboxyethyl]-2-azetidinone (XX) with CDIin THF] in the presence of Et3N to yield ketoester (XXI).Azidation of intermediate (XXI) with C12H25-Ph-SO2N3 in thepresence of Et3N in CH2Cl2 provides diazo compound (XXII),which is O-deprotected using HCl in CH2Cl2/MeOH/H2O toproduce alcohol (XXIII). Intramolecular cyclization of compound(XXIII) in the presence of Rh(O-Oct)2 in refluxing CH2Cl2 affords azabicyclo[3.2.0]heptane derivative (XXIV),which is condensed with diphenyl chlorophosphate (XXV)in the presence of DIEA and DMAP in CH2Cl2 to furnishenol phosphate (XXVI). Coupling of phosphate (XXVI) with1-(4,5-dihydro-1,3-thiazol-2-yl)azetidine-3-thiol hydrochloride(XIa) using DIEA in acetonitrile gives tebipenem pivoxil(XXVII) (11), which is finally treated with HBr in MEK, i-PrOH,dioxane or acetone (12). Scheme 2
  • 25
  • [ 692779-24-1 ]
  • [ 179337-57-6 ]
  • [ 161715-24-8 ]
YieldReaction ConditionsOperation in experiment
Stage #1: (4R,5R,6S)-6-[(1R)-1-trimethylsilyloxyethyl]-3-diphenylphosphoryloxy-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid pivaloyloxymethyl ester; 1-(4,5-dihydro-1,3-thiazol-2-yl)-3-mercaptoazetidine hydrochloride With N-ethyl-N,N-diisopropylamine In acetonitrile at 0℃; for 1.9h; Stage #2: With water; citric acid In ethyl acetate Stage #3: With potassium hydrogencarbonate In water; ethyl acetate 1 Example 1: Production of pivaloyloxymethyl(1R,5S,6S)-2-[1-(1,3-thiazolin-2-yl)azet idin-3-yl] thio-6-[(1R)-1-hydroxyethyl]-1-methyl-carbapen-2-em-3-carboxylate [] In 15 ml of acetonitrile, was dissolved 4.53 g of a yellow oily residue containing (4R,5R,6S)-6-[(1R)-1-trimethylsilyloxyethyl]-3-diphenylph osphoryloxy-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid pivaloyloxymethyl ester synthesized in Reference Example 2. To the resulting solution, was added 1.10 g (5.1 mmol) of a compound represented by formula (18) : [] and was dropwise added 1.8 ml (10.3 mmol) of diisopropylethylamine under cooling with ice, followed by stirring the mixture for 1.9 hours at the same temperature. After the completion of the reaction, the solvent was removed by evaporation from the mixture, followed by adding 40 ml of ethyl acetate and 100 ml of water. The resulting solution was washed with aqueous potassium bicarbonate solution and aqueous sodium bicarbonate solution. To the resulting ethyl acetate solution, was added aqueous citric acid solution to make the solution acidic, thereby extracting the target compound into the water phase. It was extracted again into the ethyl acetate phase by adding 50 ml of ethyl acetate and potassium bicarbonate. The solvent was removed by evaporation from the solution until the weight of the solution is reduced to 12 g. To the resulting solution, was added 25 ml of heptane to precipitate a crystal, which was filtered and washed to obtain 1.87 g of a white crystal containing the title compound. NMRδ (CDCl3): 1.23 (9H, s), 1.23 (3H, d, J = 7.1), 1.34 (3H, d, J = 6. 4 Hz), 3.13-3.21 (1H, m), 3.23 (1H, dd, J=2.7, 6.8 Hz), 3.37 (2H, t, J = 7.6 Hz), 3.94-4.03 (4H, m), 4.10-4.26 (3H, m), 4.36-4.42 (2H, m), 5.84 (1H, d, J = 5.5 Hz), 5.97 (1H, d, J = 5.5 Hz)
YieldReaction ConditionsOperation in experiment
14.i Example 14 (i) There was dissolved 700 mg of 3-mercapto-1-(1,3-thiazolin-2-yl)azetidine hydrochloride (8), which was obtained in the above Example 6, in 15 ml of a mixed solvent composed of water, acetonitrile and chloroform, and, to the resulting solution, there was added 1668 mg of p-nitrobenzyl (1R,5R,6S)-2-(diphenylphosphoryloxy)-6-[(R)-1-hydroxyethyl]-1-methyl-carbapen-2-em-3-carboxylate (14). To the obtained solution which was being cooled with ice, there was added 2.8 ml of diisopropylethylamine in the stream of nitrogen, and the resulting mixture was stirred at the same temperature for two hours. To the reaction liquid, there was added ethylacetate, and the resulting solution was washed with a saturated aqueous solution of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, and, then, the solvent was evaporated in a vacuum, and the obtained residue was subjected to silica gel column chromatography (eluent: chloroform-acetone), and, thus, there was produced 1339 mg (yield: 92%) of p-nitrobenzyl (1R,5S,6S)-2-[1-(1,3-thiazolin-2-yl)azetidin-3-yl]thio-6-[(R)-1-hydroxyethyl]-1-methyl-carbapen-2-em-3-carboxylate (15). 1 H-NMR (CDCl3) δ: 1.235 (d, 3H, J=7.26 Hz), 1.349 (d, 3H, J=6.27 Hz), 3.160 (quintet, 1H, J=7.26 Hz), 3.265 (dd, 1H, J=2.3, 6.26 Hz), 3.367 (t, 2H, J=7.26 Hz), 3.898~4.038 (m, 4H), 4.071~4.147 (m, 1H), 4.212~4.278 (m, 2H), 4.372 (2H, J=7.92 Hz), 5.255 and 5.517 (d(AB), 2H, J=13.85 Hz), 7.665 (d, 2H, J=8.58 Hz), 8.226 (d, 2H, J=8.58 Hz)
  • 27
  • [ 161715-28-2 ]
  • [ CAS Unavailable ]
  • [ 179337-57-6 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; potassium hydroxide In methanol; isopropyl alcohol 6 Example 6 STR86 There was dissolved 12.98 g of 3-acetylthio-1-(1,3-thiazolin-2-yl)azetidine (7) obtained in the above Example 5 into 58.3 ml of isopropylalcohol, and to the resultant solution which was being cooled with ice, there was added 37.3 ml solution (1.69N) of potassium hydroxide dissolved in methanol, and the resultant solution was stirred for 10 minutes. Then, at the same temperature, 66 ml solution (2N) of hydrochloric acid in methanol was added to the above solution so that it might be quenched, and, after the resultant mixture was stirred for 15 minutes at a room temperature, insoluble matters were removed by filtration. The residue obtained by condensing the filtrate was dissolved in 39 ml of isopropylalcohol, and, after insoluble matters were removed by filtration, the filtrate was condensed. To the obtained residue, there was added 58.5 ml of n-butanol so that the residue might be condensed, and, thus, there was obtained 3-mercapto-1-(1,3-thiazolin-2-yl)azetidine hydrochloride (8) in the form of yellowish white solid. To this solid, there was added 22.8 ml of acetonitrile, and the resulting mixture was stirred at a room temperature for 15 minutes so that the mixture might be dissolved, and, then, 113.4 ml of acetone was added dropwise over a period of 30 minutes. Then, further 113.4 ml of acetone was added dropwise over a period of 15 minutes, and, then, the resultant solution was stirred for 30 minutes while cooled with ice. The solid which was deposited was taken by filtration, and then was washed with 150 ml of acetone, and next was dried for a day under reduced pressure, and, thus, there was obtained 10.419 (purity: 97.5%; yield: 80.3%) of 3-mercapto-1-(1,3-thiazolin-2-yl)azetidine hydrochloride (8) in the form of colorless needle crystal. 1 H-NMR (CDCl3) δ: 2.57 (d, 1H, J=8.2 Hz), 3.59 (t, 2H, J=7.4Hz), 4.02-4.18 (m, 4H), 4.63 (t, 2H, J=7.4 Hz), 5.19-5.26 (m, 1H), 12.19 (s, 1H)
  • 28
  • [ 1904597-76-7 ]
  • [ 179337-57-6 ]
YieldReaction ConditionsOperation in experiment
85.5% With hydrogenchloride; triphenylphosphine In tetrahydrofuran; methanol; water; acetonitrile at 20℃; for 3.5h; 7 1 - (4,5-dihydro-thiazol-2-yl)-azetidine-3-thiol hydrochloride (1) synthesis of The 2 - (3 - (2 - (1 - (4,5-dihydro-thiazol-2-yl)-azelidinyl) dithio) azetidin-1-yl) - 4,5-dihydro-thiazole dihydrochloride 1g (0.0024mol), triphenylphosphine 0.468g (0.0018mol), acetonitrile 0.72 ml, water methanol mixed solution stirring the mixture at room temperature hydrogen chloride 0.055g and 0.45mL8N 1.5h, then adding 11 ml tetrahydrofuran to continue stirring 2h, filtering, using ethylene the nitrile is heavy crystallization 0.43g, yield 85.5%, melting point 125-127°C.
  • 29
  • [ CAS Unavailable ]
  • [ 179337-57-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
97% Stage #1: 4-nitrobenzyl (4R,5R,6S)-3-((diphenoxyphosphoryl)oxy)-6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate; 1-(4,5-dihydro-1,3-thiazol-2-yl)-3-mercaptoazetidine hydrochloride In acetonitrile at 20℃; for 0.166667h; Stage #2: With N-ethyl-N,N-diisopropylamine In acetonitrile at -20℃; for 10h; 1.1 syntheisis of (4R,5S,6S)-3-((1-(4,5-dihydro-1,3-thiazol-2-yl)azetidin-3-yl)thio)-6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carbonyl 4-nitrobenzoate in a dry three necked flask added 6-MAP(148.60g), 3-Mercapto Azetidine hydrochloride(60.70g) and acetonitrile(1000ml) and stirred for 10min at room temperature . followed by cooling down the reaction to -20°C then slowly added DIPEA (71.30g) and reaction was allowed to react for 10h at same temperature. In the reaction system added water (600ml) and after raising the temperature to 10°C the reaction was stirred for 30min.filteration was carried out, the resulting filtrate washed with mixture of acetonitrile /water(volume ratrio 1:1,300ml) then washed with Isopropyl alcohol (300 ml)and dried in a vacuo to obtain (4R,5S,6S)-3-((1-(4,5-dihydro-2-thiazolinyl) -3-Azetidinyl) thio)-6-((R)-1-hydroxyethyl) -4-methyl-7-oxo-1-azabicyclo [3.2.0] heptan-2-enyl-2-carboxylic acid p-Nitrobenzyl ester(III) 126.50g, yield 97%, directly placed into the next step reaction.
  • 30
  • [ 179337-57-6 ]
  • [ 211558-19-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: N-ethyl-N,N-diisopropylamine / 3.5 h / -20 °C 2.1: 0.5% Pd/C; sodium hydrogencarbonate; hydrogen / butan-1-ol; water / 3 h / 25 - 30 °C / 7500.75 Torr 3.1: N-benzyl-N,N,N-triethylammonium chloride; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 35 °C 3.2: 7 - 8 °C
  • 31
  • [ CAS Unavailable ]
  • [ 179337-57-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
93.8% With N-ethyl-N,N-diisopropylamine In acetonitrile at 0 - 5℃; for 2.33h; Inert atmosphere; Cooling with ice; step 1 p-nitrobenzyl (1R,5S,6S)-2-(1-(4,5-dihydro-2-thiazolyl)azetidin-3-yl)thio-6-[(1R)-hydroxyethyl]-1-methyl-2-carbapenem-3-carboxylate p-nitrobenzyl (1R,5S,6S)-2-(diphenylphosphoryloxy)-6-[(1R)-hydroxyethyl]-1-methyl-2-carbapenem-3-carboxylate (MAP, 298 g) and A solution of 116 g of 1- (4,5-dihydro-2-thiazolyl) -3-azetidinethiol hydrochloride is suspended in 2,000 mL of acetonitrile (ACN) and the temperature is maintained at 0-5 ° C. The solvent may be appropriately selected in addition to acetonitrile. Diisopropylethylamine (DIEA, 142 g) was added dropwise to the reaction solution over 20 minutes, and the reaction was continued at 0 to 5 ° C for 2 hours. When the reaction is complete, add 600 mL of distilled water and stir at the same temperature for another 30 minutes. The resulting solid is filtered off and washed with 600 mL of an acetonitrile-water (1: 1) mixed solution. The obtained solid was dried in a vacuum oven at 40 for 4 hours to obtain the target compound p-nitrobenzyl (1R,5S,6S)-2-(1-(4,5-dihydro-2-thiazolyl)azetidin-3-yl)thio-6-[(1R)-hydroxyethyl]-1-methyl-2-carbapenem-3-carboxylate (PTBP, 243.2 g, yield 93.8%, purity 95.2%).
  • 32
  • [ 179337-57-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / acetonitrile / 2.33 h / 0 - 5 °C / Inert atmosphere; Cooling with ice 2: palladium 10% on activated carbon; hydrogen; sodium hydrogencarbonate / tetrahydrofuran; water / 2 h / 15 - 25 °C
  • 33
  • [ 179337-57-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine / acetonitrile / 2.33 h / 0 - 5 °C / Inert atmosphere; Cooling with ice 2: palladium 10% on activated carbon; hydrogen; sodium hydrogencarbonate / tetrahydrofuran; water / 2 h / 15 - 25 °C 3: N-benzyl-N,N,N-triethylammonium chloride; triethylamine / N,N-dimethyl-formamide / 55 - 70 °C
  • 34
  • [ CAS Unavailable ]
  • [ 179337-57-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
98.5% With N-ethyl-N,N-diisopropylamine In water; acetonitrile at -4 - 5℃; Inert atmosphere; 3 Example 3 Acetonitrile 2.5L was added to a 10L reaction flask under a nitrogen atmosphere, and the temperature was lowered to -4 to 5C. 256.5 g (0.432 mol) of Compound 2 (MAP) and 100 g (0.475 mol) of Compound 3 (TAT) were added, and the mixture was stirred well.DIPEA (56.0 g, 0.433 mol) was slowly added dropwise at -4 to 5°C, and the dropwise addition time was controlled at 1 to 2 hours.After completion of the dropwise addition, the reaction was incubated at -4 to 5°C for 3 hours, and the reaction was monitored by TLC (methanol:ethyl acetate=1:4) until the reaction was completed.5L of water was added to a four-mouth bottle, and the temperature was raised to 0-5°C, and the temperature was kept stirring for 0.5 to 1 hour.After completion of heat preservation, suction filtration, solid 250.6g, ethanol 2506g at 20-25°C, beating for 60 minutes, filtration, vacuum drying of filter cake to obtain 220.4g solid, yield 98.5%, purity 99.8%.
With N-ethyl-N,N-diisopropylamine In acetonitrile at -4 - 5℃; Inert atmosphere; 1.1 Example 1: This example provides a preparation method of an epicient penic acid ester intermediate, and the steps of the preparation method are as follows: (1) Add 2.5 L of acetonitrile to a 5 L reaction flask under nitrogen protection, cool to -4 to 5 ° C, add 0.432 mol of compound 2, 0.475 mol of compound 3, and mix well.Slowly add 0.433 mol of N,N-diisopropylethylamine at -4 to 5 °C.The dropping time is controlled in 1 to 2 hours. After the addition is completed,The reaction was kept at -4 to 5 ° C for 3 hours. Then, the reaction was monitored by thin layer chromatography (developing solvent: methanol: ethyl acetate = 1: 4) until the reaction was completed, and 1.25 L of water was added to the reaction flask, and the mixture was heated to 0 to 5 ° C, and kept under stirring for 0.5 hour.After the heat preservation is completed, suction filtration, using anhydrous ethanol at 20 to 25 ° C,Beating for 30 minutes, filtering, filter cake vacuum drying to obtain intermediate compound 4
  • 35
  • [ 179337-57-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine / acetonitrile; water / -4 - 5 °C / Inert atmosphere 2: 5%-palladium/activated carbon; hydrogen; sodium hydrogencarbonate / water; butan-1-ol / 3 h / 20 - 25 °C / 2850.29 - 3375.34 Torr / Autoclave 3: N-benzyl-N,N,N-triethylammonium chloride; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 4.25 h / 25 - 40 °C / Inert atmosphere
  • 36
  • [ 179337-57-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / acetonitrile; water / -4 - 5 °C / Inert atmosphere 2: 5%-palladium/activated carbon; hydrogen; sodium hydrogencarbonate / water; butan-1-ol / 3 h / 20 - 25 °C / 2850.29 - 3375.34 Torr / Autoclave
  • 37
  • [ CAS Unavailable ]
  • [ 179337-57-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
50% With N-ethyl-N,N-diisopropylamine In acetonitrile at 0℃; for 2h; 2 Allyl (5S,6R)-3-((l-(4,5-dihydrothiazol-2-yl)azetidin-3-yl)thio)-6-((R)-l- hydroxyethyl)-7-oxo-4-thia-l-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (5b). General procedure: A solution of l-(4,5-dihydro-2-thiazolyl)-3-azetidinethiol hydrochloride (3.10 g, 14.74 mmol) in acetonitrile (50 mL) followed by diisopropylethylamine (3.70 mL, 20.77 mmol) were added to a stirring solution of 4 (4.63 g, 13.4 mmol) in acetonitrile (100 mL) and the mixture was stirred for 2 h at 0 °C. The solution was diluted with brine and the aqueous layer was back extracted three times with ethyl acetate. The combined organic layers were dried with anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude oil was purified by silica gel chromatography (methanol:dichloromethane, 1:40) to provide 5b as a yellow oil that became a glass under high vacuum (2.85 g, 50%). 5b: TLC (methanol :dichloromethane, 1:19) = 0.3. lH NMR (400MHz, CDC13)□ = 5.94(tdd,J=5.4, 10.7, 17.2 Hz, 1 H), 5.69 (d,J= 1.4 Hz, 1 H), 5.41 (qd,J= 1.5, 17.1 Hz, 1 H), 5.24 (qd,J= 1.2, 10.5 Hz, 1 H), 4.77 (tdd,J= 1.4, 5.5, 13.4 Hz, 1 H), 4.67 (tdd, J= 1.4, 5.6, 13.4 Hz, 1 H), 4.40 (td, J= 8.4, 23.9 Hz, 3 H), 4.19 (sxt, J = 6.5 Hz, 1 H), 4.25 - 4.10 (m, 1 H), 4.00 (t, J= 7.4 Hz, 2 H), 4.06 - 3.90 (m, 2 H), 3.72 (dd,J= 1.5, 6.9 Hz, 1 H), 3.36 (t, J= 7.4 Hz, 2 H), 1.33 (d, J = 6.5 Hz, 3 H). 1 C NMR(101MHz,CDCl3)5 = 172.2, 164.4, 159.5, 152.1, 131.6, 118.5, 117.6, 71.5, 65.8, 65.2, 65.0, 60.4, 59.3, 58.7, 36.2, 36.1, 21.9. HRMS (FAB), C17H22N3O4S3 [M+H+] calculated: 428.0773; found: 428.0765; Δ 1.8 ppm.
  • 38
  • [ 179337-57-6 ]
  • [ 1904597-76-7 ]
YieldReaction ConditionsOperation in experiment
25.1 g With potassium iodate; sodium iodide In water at 30℃; 3 Alternatively the 44.3g crude ester side chain and Bipei Nan0.1g sodium iodide added to 90ml water,Add saturated potassium iodate solution at 30°CAfter the reaction was detected by TLC,Add 90ml ethyl acetate, stir for 10min,Dispense liquid, discard the organic layer, adjust the pH of the aqueous layer with sodium bicarbonate solution to 11~12, and filter.Dried to white solid 25.1g, yield 96.5%.
  • 39
  • [ 1904597-76-7 ]
  • [ 179337-57-6 ]
YieldReaction ConditionsOperation in experiment
97.9% With hydrogenchloride; triphenylphosphine In ethanol; water at 30℃; 1 Example 1 Add in 250ml three-necked flask13.9 g (40 mmol) of the white solid obtained above,11.0 g (42 mmol) of triphenylphosphine,36% hydrochloric acid 8.5g (HCl 84mmol) and70 ml of ethanol, stir and warm up to 30 °C,Insulation reaction, TLC monitoring reactionUntil the raw material is completely converted. The reaction solution was warmed to 50 °C and concentrated to dryness under reduced pressure. After dissolving it with 20 ml of ethanol, the solution was heated.The temperature dropped to 05°C, and 100ml isopropyl ether was slowly added dropwise.After the drop was incubated for 1 hour, the mixture was filtered and dried to obtain 16.5 g of white solid powder. The yield was 97.9%.HPLC purity 99.8%.
  • 40
  • [ 189188-38-3 ]
  • [ 179337-57-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With triethylamine In acetonitrile at -3℃; for 1.5h; 1.1 step 1:0.5 mol of the first raw material, 0.515 mol of the second raw material, 4 L of the solvent, and 0.3 mol of the first acid binding agent were sequentially added to the reaction vessel, and the reaction temperature was controlled to -3 ° C, and the reaction time was 1.5 h.After the completion of the reaction, 5 L of pure water was added to the system, and then filtered under reduced pressure to obtain a cake. 2.5 L of isopropanol was added to the cake, stirred at room temperature, filtered under reduced pressure and dried to give a condensate. ;
  • 41
  • [ CAS Unavailable ]
  • [ 179337-57-6 ]
  • [ 161715-20-4 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In acetonitrile at 0℃; for 4h; 1-3 Using 110 kg of acetonitrile as the solvent, add MAP and YKTP-1 into the reactor at a ratio of 1:1.2:2.1, control the temperature at 0°C, add N,N-diisopropylethylamine dropwise, and stir for 4 hours. 70kg of purified water was added dropwise, stirred and centrifuged; the filter cake was rinsed with acetonitrile-water mixture, isopropanol, and ethyl acetate respectively. It was dried under vacuum for 12 hours, and it was almost white (YKTP-2).
  • 42
  • [ 179337-62-3 ]
  • [ CAS Unavailable ]
  • [ 179337-57-6 ]
YieldReaction ConditionsOperation in experiment
Stage #1: 3-methanesulfonyloxy-1-(1,3-thiazolin-2-yl)azetidine; thiolacetic acid potassium salt In N,N-dimethyl-formamide at 100℃; Stage #2: With potassium hydroxide In methanol; isopropanol Other alternative routes to obtain the keyintermediate (XIa) b) Reaction of benzhydrylamine (XXXVII) with epichlorohydrin(XXIX) in MeOH gives 1-(benzydrylamino)-3-chloro-2-propanol(XXXVIII), which upon intramolecular cyclizationin DMSO provides 1-benzhydryl-3-hydroxyazetidinehydrochloride (XXXIX). Hydrogenolysis of benzhydryl amine(XXXIX) over Pd/C in EtOH/H2O affords 3-hydroxyazetidinehydrochloride (IV) (15, 16), which is condensed with2-(methylsulfanyl)-2-thiazoline (VII) in the presenceof KHCO3in MeOH to furnish 1-(4,5-dihydro-2-thiazolyl)-3-azetidinol(VIII). Treatment of alcohol (VIII) with MsCl in the presenceof DMAP and Et3N in THF yields the corresponding mesylate(IX), which is then substituted with CH3COSK in DMF at100 °C, followed by hydrolysis of the resulting acetate (X) bymeans of KOH in i-PrOH/MeOH (15). Scheme 4.
  • 43
  • [ 1392406-55-1 ]
  • [ 179337-57-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
8.2 g With N-ethyl-N,N-diisopropylamine In acetonitrile at 0℃; for 3h; Inert atmosphere;
Same Skeleton Products
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[ 179337-57-6 ]

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1-Benzylazetidin-3-ol

Chemical Structure| 18621-17-5

[ 18621-17-5 ]

1-Benzhydrylazetidin-3-ol

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[ 161715-21-5 ]

Tebipenem

Chemical Structure| 76855-69-1

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(2R,3R)-3-((R)-1-((tert-Butyldimethylsilyl)oxy)ethyl)-4-oxoazetidin-2-yl acetate