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Chemical Structure| 827-16-7 Chemical Structure| 827-16-7

Structure of 827-16-7

Chemical Structure| 827-16-7

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Product Details of [ 827-16-7 ]

CAS No. :827-16-7
Formula : C6H9N3O3
M.W : 171.15
SMILES Code : O=C(N(C)C(N1C)=O)N(C)C1=O
MDL No. :MFCD00179925
InChI Key :AHWDQDMGFXRVFB-UHFFFAOYSA-N
Pubchem ID :13225

Safety of [ 827-16-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 827-16-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.5
Num. rotatable bonds 0
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 43.01
TPSA ?

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

66.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.62
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

-0.62
Log Po/w (WLOGP)?

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

-2.22
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.

-0.93
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

-0.93
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.61

Water Solubility

Log S (ESOL):?

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

-0.88
Solubility 22.5 mg/ml ; 0.132 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-0.29
Solubility 87.0 mg/ml ; 0.508 mol/l
Class?

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

Very 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

0.32
Solubility 356.0 mg/ml ; 2.08 mol/l
Class?

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

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

No
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

No
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

No
Log Kp (skin permeation)?

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

-7.78 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

0.0
Egan?

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

0.0
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

1.0
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

0.0 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<1.0
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)

1.67

Application In Synthesis of [ 827-16-7 ]

* 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 [ 827-16-7 ]

[ 827-16-7 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 6642-30-4 ]
  • [ 124-41-4 ]
  • [ 827-16-7 ]
  • 3
  • [ 6642-30-4 ]
  • calcium hydroxide [ No CAS ]
  • [ 827-16-7 ]
  • 4
  • [ 67-56-1 ]
  • [ 598-55-0 ]
  • [ 827-16-7 ]
  • [ 75-13-8 ]
  • [ 115-10-6 ]
  • [ 6642-30-4 ]
  • [ 616-38-6 ]
YieldReaction ConditionsOperation in experiment
dibutyldimethoxytin; In Triethylene glycol dimethyl ether; at 173.879℃; under 5311.07 Torr; for 1500h; The purpose of this experiment is demonstrating a primary reactor system, which is composed of multiple reactors. The same experimental set-up in Example 2 was used to demonstrate the performance of the second primary reactor. The experiment was carried out in the similar manner to the Experiment 2. The present example differs from the Example 2 in that the 8 wt. % DMC solution in methanol is used herein in the place of pure methanol in the Experiment 2 and a slightly lower overhead pressure (88 psig) in the present distillation column. The reboiler of the distillation column was loaded with the following materials; 285 grams of triglyme, 40 grams of methanol and 100 grams of dibutyltin dimethoxide. A steady state operation of the distillation column reactor was obtained, while pumping in MC solution and DMC-methanol solution to the reactor. The reactor operation was continued for more than 1500 hours without interruption at 345 F. for the liquid reaction medium in the reboiler, the distillation column temperature of 278 F., and 88 psig for the overhead column pressure. The average compositions of the overhead and bottom products from the reactor during the 54 hours from 1428 hours to 1482 hours of on-stream-time are listed in Table 2. During this period, the pumping rate of a 22.5 wt. % MC solution (590 ppm H2O) was fixed at 1.97 ml/min and the pumping rate of a 8 wt. % DMC solution (80 ppm H2O) was about 3.2 ml/min at 345 F. The mole ratio of MC/CH3OH and DMC wt. % based on MC and CH3OH in the liquid medium in the reactor are 0.915 and 6.40 wt. % respectively. The result of the experiment corresponds to better than 93 mole % of MC to DMC.
  • 5
  • [ 67-56-1 ]
  • [ 598-55-0 ]
  • [ 827-16-7 ]
  • [ 115-10-6 ]
  • [ 6642-30-4 ]
  • [ 616-38-6 ]
YieldReaction ConditionsOperation in experiment
dibutyldimethoxytin; In Triethylene glycol dimethyl ether; at 173.879℃; under 5455.88 Torr; for 926h; A one liter stirred autoclave serves as the reaction zone and reboiler for the reaction/distillation column reactor, which is connected to a 1 inch diameter×3.5 feet long distillation column. The distillation column has three zone heaters, which are independently controlled. The overhead vapor stream from the distillation column is diluted with a nitrogen stream (800 cc/min) and then partially cooled to about 200 F. with hot water in a condenser. The vapor stream from the condenser cooled to ambient temperature to prevent the plugging problem of a cold spot and overhead backpressure regulator. The liquid stream from the condenser flows to a small overhead liquid reflux drum. The temperature of the liquid reflux drum is maintained at ambient temperature. The flow of the liquid product from the overhead reflux drum is monitored with a LFM (liquid flow meter). The liquid stream from the overhead reflux drum and the cooled vapor stream are combined as product stream from the reaction/distillation reactor. Samples are taken for analyses to determine the composition of the overhead vapor stream coming out of the column. Also occasionally samples are taken from the reboiler to monitor the composition of the liquid reaction medium. Whenever the samples are taken from the reboiler, the make-up solutions are pumped in to compensate for the loss of triglyme and catalyst. During the operation of the reactor, the liquid level inside the reboiler is maintained at a constant level. A vertical sight glass is attached to the reboiler for the visual observation of the liquid level inside the reboiler during the operation. Also the reboiler is equipped with a liquid level digital monitor for the automatic control of the reactor during the night and weekends for unattended operation. To carry out the operation of the primary reactor to produce DMC, a MC feed solution (methyl carbamate in methanol) and a methanol feed are pumped in and combined into a single stream. The combined feed stream is passed through a prereactor (a vertically mounted tubular reactor up-flow) at 300 F. and 230 psig to remove water in the feed streams and then introduced to the primary reactor. The temperature of the liquid reaction medium is controlled by adjusting the overhead pressure of the distillation column and the concentration of high boiling solvent in the reboiler of the distillation column. The products DMC, ammonia and other light by-products such as dimethyl ether and CO2 are boiled off from the liquid medium and carried away along with methanol vapor. The operation of the distillation column is carried out in the unconventional mode to perform partial condensation of the vapor coming out of the liquid medium in the reboiler without liquid reflux from the overhead reflux drum by controlling the vapor temperature, which is done by controlling the zone temperatures of the column with three column zone heaters, while the vapor is coming up the distillation column. It was discovered that the unconventional column operation keeps the triglyme solvent in the reactor and continuously removes the by-product N-MMC along with MC from the liquid reaction medium as a part of the overhead stream, which allows the operation of the reactor for an extended period of time. It is found that no liquid reflux from the overhead reflux drum is highly preferred in minimizing the formation of the by-product N-MMC and heterocyclic compounds. It was possible to operate the reaction/distillation column reactor more than 1000 hours without interruption until a high pressure nitrogen valve to the reboiler was accidentally opened. Operating the distillation column in the conventional way causes shutdown or removal of materials from the reboiler, because of the overflow of the reboiler due to the accumulation of the reaction by-products such as N-MMC, cyanuric acid and TTT (1,3,5-trimethyl triazine-2,4,6-trione), etc. Other critical factors to minimize the side-reactions while maintaining an acceptable DMC production rate are balancing the concentrations of solvent and catalyst, the temperature of liquid medium and the overhead column pressure. The range of optimum operation for the reboiler temperature and the overhead column pressure is from about 330 to about 355 F. for the reboiler temperature and from about 80 to about 110 psig respectively. Detailed Description of the Experiment The reboiler of the distillation column was loaded with the following materials; 285 grams of triglyme, 100 grams of methanol and 100 grams of dibutyltin dimethoxide. A steady state operation of the reaction/distillation column reactor was obtained, while pumping in the 13.3 wt. % MC solution in methanol (280 ppm H2O) at a fixed rate of 3.01 ml/min and about 1.92 ml/min of methanol (80 ppm H2O) at 345 F. for the liquid reaction medium in the reboiler, 260 F. for the vapor temperature in the top section of the distillation column, and 90.8 psig for the overhead column pressure. The flow rate...
 

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