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Chemical Structure| 89604-92-2 Chemical Structure| 89604-92-2

Structure of 89604-92-2

Chemical Structure| 89604-92-2

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Product Details of [ 89604-92-2 ]

CAS No. :89604-92-2
Formula : C20H22N4O4S3
M.W : 478.61
SMILES Code : CC(C)(C)OC(=O)C(C)(C)ON=C(C(=O)SC1=NC2=C(S1)C=CC=C2)C1=CSC(N)=N1
MDL No. :MFCD00071548

Safety of [ 89604-92-2 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302+H312+H332-H315-H319-H228
Precautionary Statements:P261-P210-P264-P280-P370+P378-P302+P352+P312
Class:4.1
UN#:1325
Packing Group:

Computational Chemistry of [ 89604-92-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 31
Num. arom. heavy atoms 14
Fraction Csp3 0.35
Num. rotatable bonds 9
Num. H-bond acceptors 7.0
Num. H-bond donors 1.0
Molar Refractivity 125.5
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

198.54 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

3.73
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

5.64
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

4.5
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

1.26
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

5.29
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

4.09

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-6.1
Solubility 0.00038 mg/ml ; 0.000000793 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Poorly soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-9.57
Solubility 0.000000128 mg/ml ; 0.0000000003 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Poorly soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-5.49
Solubility 0.00156 mg/ml ; 0.00000327 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

Low
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

No
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

Yes
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

Yes
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

Yes
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.22 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

1.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

1.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

2.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

3.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<3.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

4.07

Application In Synthesis of [ 89604-92-2 ]

* 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 [ 89604-92-2 ]

[ 89604-92-2 ] Synthesis Path-Downstream   1~13

  • 1
  • [ 89604-92-2 ]
  • C31H43F3N5O6SSi2(1+)*I(1-) [ No CAS ]
  • C44H60F3N8O10S2Si2(1+)*I(1-) [ No CAS ]
  • 2
  • [ 89604-92-2 ]
  • [ 135327-68-3 ]
  • C39H43FN8O12S2 [ No CAS ]
  • 3
  • [ 89604-92-2 ]
  • (6R-trans)-7-amino-3-<<4-(3-carboxy-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-quinolinyl)-1-piperazinyl>methyl>-8-oxo-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxylic acid trifluoroacetic acid salt [ No CAS ]
  • 6R-<6α,7β(Z)>-7-<<<(2-amino-4-thiazolyl)<<(1,1-dimethylethoxy)carbonyl>-1-methylethoxy>imino>acetyl>amino>-3-<<4-(3-carboxy-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-quinolinyl)-1-piperazinyl>methyl>-8-oxo-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-ca... [ No CAS ]
  • 4
  • [ 89604-92-2 ]
  • [ 127142-88-5 ]
  • 5
  • [ 89604-92-2 ]
  • [ 127142-81-8 ]
  • 6
  • 1-[[(6R,7R)-7-amino-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-3-yl]methylpyridinium hydroxide [ No CAS ]
  • [ 89604-92-2 ]
  • 1-[[(6R,7R)-7-[(Z)-(2-amino-4-thiazolyl)-2-[[1-(t-butoxycarbonyl)-1-methylethoxy]imino]-acetamido]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]pyridinium hydroxide [ No CAS ]
YieldReaction ConditionsOperation in experiment
In methanol; dichloromethane; water; acetone; EXAMPLE 10 3.64 g of 1-[[(6R,7R)-7-amino-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-3-yl]methylpyridinium hydroxide internal salt dihydrochloride are dissolved in 250 ml of methanol. 5.74 g of S-(2-benzothiazolyl)-2-amino-alpha-[(Z)-[1-(t-butoxycarbonyl)-1-methylethoxy]-imino]-4-thiazole-thioacetate and 150 ml of methylene chloride are now added thereto and the mixture is stirred at 20°-25° for 2 hours. The yellow solution obtained is evaporated in a water-jet vacuum at 30° and the residue is triturated with 100 ml of acetone. The solid is filtered off under suction, washed with acetone and dried in a vacuum at 25°. The material obtained (5.6 g of a beige amorphous solid) is partitioned between 50 ml of water and 50 ml of methylene chloride. The aqueous phase is separated, washed twice with methylene chloride and lyophilized overnight in a high vacuum. There are obtained 4.2 g (62.2percent) of 1-[[(6R,7R)-7-[(Z)-(2-amino-4-thiazolyl)-2-[[1-(t-butoxycarbonyl)-1-methylethoxy]imino]-acetamido]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]pyridinium hydroxide internal salt dihydrochloride as a beige lyophilizate (C26 H30 N6 O7 S2.2HCl; MW: 675.603).
  • 7
  • [ 80082-65-1 ]
  • [ 89604-92-2 ]
  • [ 330944-50-8 ]
YieldReaction ConditionsOperation in experiment
To a suspension of Azetidine of formula III (25 g) in mixture of aq.acetone or aq.THF, triethylamine (29 mL) was added. To the reaction mass, TAEM of formula (IV) (75 g) was added and the reaction mass was stirred at 150C -2O0C till completion of reaction. After completion of reaction was added a mixture of ethyl acetate and water (1 :1) and pH adjusted to 5.0. The by products obtained were removed, and layers separated. Organic layer was again extracted with water. The pH of the aqueous layer was acidified to 2.0 with dil. HCl at 00C -50C. The solid obtained was filtered, washed with water and dried under vacuum at 4O0C to yield title compound in pure form (48 g)
5.4 g Azetidin is dissolved in 20 ml acetonitrile (or dimethyl formamide) with the assistance of 5 ml of triethylamine at room temperature. The solution is cooled to [0°C.] A solution of 4 g TAEM in 25 ml THF is added with magnetic stirring. If the color disappears, 8 g TAEM in 50 ml THF is added. After 10 minutes, another 4.1 g TAEM in 25 ml THF is added. The solution is stirred at [0°C] for an additional hour. The pH is adjusted to about 4-5 with a freshly prepared TFA solution (TFA-THF 1: 4, [V/V).] Being careful not to evaporate the acetonitrile, the THF is evaporated (weight loss is about 90 g) at30°C under vacuum. The remaining residue is diluted with 200 ml ethylacetate and then extracted with 100 ml and then 50 ml of distilled water. The aqueous extracts are combined and washed twice with 50 ml ethylacetate after readjustment of the pH to about 4-5. The dissolved ethylacetate is removed from the aqueous phase by vacuum at [30 °C.] 10-15 g [KC1] (or NaCl) is dissolved. The solution is acidified with [HC1] solution (cc. [HCL-DISTILLED] water 1: 4, [V/V)] with stirring (approx. 10 ml). The solution is cooled to [0 ° C] with slow stirring and crystallization occurs. The resulting suspension is refrigerated overnight (at about [5 °C).] The suspension is filtered on a glass filter, and the crystals are washed with chilled water. The washed crystals are dried at room temperature. The product, Aztreonam t-butyl ester, is about 12.5-13 g white solid, which is sufficiently pure for the next step.
65 g Azetidine is dissolved in a mixture of 240 ml acetonitrile and 60 ml triethylamine. When dissolution is complete, TAEM is added in four portions. The suspension is stirred for 20-30 min, then diluted with 500 ml EtOAc and 500 ml water and stirred for [5-10 MIN.] The pH of the emulsion is set to 5 with 2.4 M [HC1] solution. After the phases separate, the pH of the aqueous phase is checked. If the pH is between 4.20 and 5.30, the two phases are filtered and separated, otherwise more [HC1] is added. The upper phase is diluted with 900 ml ethylacetate and extracted with 2 x 500 ml water (faster phase separation). The combined aqueous phase is diluted with 500 ml water and washed with 2 x 500 ml ethylacetate. The dissolved ethylacetate is removed from the aqueous phase by vacuum. The aqueous phase is acidified further to pH 2 with 2.4 M [HC1] solution. The solution is stirred and cooled. Crystallization starts soon. The suspension is stirred and cooled to [0 °C,] stirring at this temperature overnight. The suspension is filtered, washed with chilled water, dried at 38 [°C] in air-circulated oven for 3 h. The yield is approx. 116-120 g of Aztreonam t-butyl ester.
  • 8
  • [ 89604-92-2 ]
  • [ 100988-63-4 ]
  • [ 102772-66-7 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In methanol; dichloromethane; at 0℃; for 24h; 19.1 g of 2-(2-amino-4-thiazolyl)-(Z)-2-[(l-tert.butoxycarbonyl-l- methylethoxy)imino]thioacetic acid-S-benzothiazol-2-yl-ester, 14.6 g of (6R,7R)-7-amino-3-(l-pyridiniummethyl)-3-cephem-4-carboxylic acid iodide, monohydrate and 5.6 ml of triethylamine were stirred for 24 hours at 0 C in a mixture of 142.5 ml of dichloromethane and 7.5 ml of methanol. The solid substance was filtered off, washed with dichloromethane and vacuum-dried at room temperature. 16.0 g of the title compound were obtained in crystalline form. This compound was optionally stirred with acetone followed by filtration yield to get pure (6R,7R)-7-[[2-(2-amino-4-thiazolyl)-(Z)-2-(tert.butoxycarbonyl-l- methylethoxy)imino]acetamido]-3-(l-pyridiniummethyl)-3-cephem-4- carboxylate. This compound thus obtained was treated with HCL in formic acid at 25 C for two hrs. After the completion of the reaction, ethyl acetate was added to the reaction mass and the layers were separated. The aqueous layer was treated with Amberlite resin to adjust the pH to 4.0. The product was filtered, slurry washed with acetone and dried to get Ceftazidime pentahydrate in pure form.
  • 9
  • [ 120-78-5 ]
  • [ 86299-47-0 ]
  • [ 89604-92-2 ]
  • [ 149-30-4 ]
  • 10
  • C5H8F2N2O5S [ No CAS ]
  • [ 89604-92-2 ]
  • C18H25F2N5O9S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
5% [00322] A 10-mL round bottom flask equipped with a stir bar was charged with core (25 mg, 0.101 mmol, 1 equiv), followed by wet tetrahydrofuran (0.400 mL). The reaction vessel was placed in an ice water cooling bath. Triethylamine (0.42 mL, 0.305 mmol, 3 equiv) was added and the cooling bath was removed after 5 minutes. The vessel continued to stir at 23 °C as (Z)-iert-butyl 2-(((l-(2-aminothiazol-4-yl)-2-(benzo[d]thiazol-2-ylthio)-2- oxoethylidene)amino)oxy)-2-methylpropanoate (73 mg, 0.152 mmol, 1.5 equiv) was added portion- wise. Reaction progress was monitored by the consumption of the core by LC-MS analysis of aliquots removed from the reaction mixture. After 2.5 h, ethyl acetate (10 mL) and water (10 mL) were added and the layers were separated. The organic layer was washed with 0.5 M aqueous hydrochloric acid solution (2 x 10 mL) and the aqueous extracts were combined and concentrated with no additional heating on the rotovap bath. The crude material was purified via HPLC (Agilent Extend-C18, 90: 10?70:30 water-acetonitrile + 0.1percent formic acid, then 100percent acetonitrile +0.1percent formic acid) to provide the coupled product (3 mg, 5percent) as an off-white solid. 1H NMR (600 MHz, CD3OD), delta: 7.14 (s, 1H), 5.33 (s, 5.00-4.83 (m, 4H), 1.60 (s, 3H), 1.59 (s, 3H), 1.47 (s, 9H). HRMS (ESI): Calcd for (C18H25F2N5O9S2 - H)": 556.0989; Found: 556.0985.
  • 11
  • [ 80082-65-1 ]
  • [ 89604-92-2 ]
  • [ 78110-38-0 ]
YieldReaction ConditionsOperation in experiment
86.9% A reaction flask was added the primary ring aztreonam (5.0g, 27.8mmol), acetonitrile (30 mL), was slowly added dropwise with stirring pyridine (2.7mL, 33.2mmol), the reaction was stirred until complete dissolution, cooled to -5 deg.] C, was added dropwise the side chain active ester compound (13.3g, 27.8mmol) in 60mL acetonitrile. after completion of the dropwise addition, the reaction was kept 4h, after completion of the reaction with dichloromethane (100mL) and 2percent formic acid (about 100mL ), neutralized to pH 6.0, filtered, the organic layer was washed with stratification, washed with water (70mL × 3), the combined aqueous layer and washings using 20percent nitric acid solution adjusted to pH 1, was slowly heated to about 35 , reaction heat 2h, active carbon was added 0.5h, filtered and the filtrate was cooled to 0 deg.] C, stirring the precipitated solid was filtered, washed with water, 40 deg.] C and dried in vacuo to give 11.0 g of crude aztreonam, 93.2percent yield, 98.9percent purity. To the reaction flask was added 10.7g aztreonam crude product (purity 98.9percent) and 40ml of distilled water, and stirred to cool under a 71/92 0 saturated aqueous sodium carbonate until the solution is clear, was added dropwise hydrochloric acid (1M), and a white precipitate.Suction filtered and the filter cake was dried in vacuo 35 .The above solid was added absolute ethanol (700mL) and heated to 60 dissolved, heating was stopped, cooled with stirring, suction filtered, the filter cake was dried in vacuo at 35 , aztreonam give beta-type compound. Give a white solid 9.3g, 86.9percent yield, 99.9percent purity.
  • 12
  • [ 120-78-5 ]
  • [ 86299-47-0 ]
  • [ 89604-92-2 ]
YieldReaction ConditionsOperation in experiment
92.6% At 21 ° C,35g cefotaxime side chain acid and 48gDMWas added to a mixture of dichloro and acetonitrile (the mass of the mixture was 250 g and the density was 1.0 g / cm 3)After stirring for 10 min,1.0 mL of pyridine was added,At 22 ° C, triethylamine (8.0 mL)After the addition was completed, the temperature was raised to 30 ° C., the reaction was incubated for 50 minutes, cooled,28 ml of triethyl phosphite was added dropwise at 21 ° C,Drop when the process of sharing 2.5h,After the addition was completed, the reaction was incubated at 21 ± 1 ° C for 3.0 h,Then cooled to 3 incubated reaction 30min, suction filtration,And dried at 60 to ceftazidime side chain acid active ester, the yield was 92.6percentThe content is 99.3percent.
  • 13
  • 1-((7-ammonio-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl)methyl)pyridin-1-ium chloride [ No CAS ]
  • [ 89604-92-2 ]
  • [ 102772-66-7 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In chloroform; tert-butyl alcohol; at 0 - 10℃;pH 7-9; 520 ml of chloroform was added to a clean and dry four-neck reaction flask, 30 ml of t-butanol was added, and the temperature was lowered to 0-5 C.Add 7-APCA 70g, pyridine active ester 105g, control the temperature to add triethylamine,Adjust the pH to 7.0-9.0. The temperature is controlled at 0-10 C for 20-24 hours. After the reaction,150 ml of pure water was added, stirred for 1-2 hours, and chloroform was separated.Isopropanol precipitation in the drug solutionThe ceftazidime tert-butyl ester was stirred and crystallized at 0-10 C for 2 hours. Filter by suction and wash with isopropyl alcohol.After drying, ceftazidime tert-butyl ester was dried.Weight yield: 145%, purity 98.9%,
 

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