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Chemical Structure| 894852-01-8

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Product Details of [ 894852-01-8 ]

CAS No. :894852-01-8
Formula : C9H9BrN2O2
M.W : 257.08
SMILES Code : CC1(C)OC2=CC(Br)=CN=C2NC1=O
MDL No. :MFCD11215488
InChI Key :RWDKWNQIMXGFDK-UHFFFAOYSA-N
Pubchem ID :57742040

Safety of [ 894852-01-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P280-P305+P351+P338-P310

Computational Chemistry of [ 894852-01-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.33
Num. rotatable bonds 0
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 58.41
TPSA ?

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

51.22 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.13
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

1.42
Log Po/w (WLOGP)?

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

1.38
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.

1.11
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

2.12
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.63

Water Solubility

Log S (ESOL):?

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

-2.65
Solubility 0.581 mg/ml ; 0.00226 mol/l
Class?

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

Soluble
Log S (Ali)?

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

-2.1
Solubility 2.04 mg/ml ; 0.00794 mol/l
Class?

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

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

-3.88
Solubility 0.0342 mg/ml ; 0.000133 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

High
BBB permeant?

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

Yes
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

Yes
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.

-6.86 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

0.0
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<0.0
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)

2.45

Application In Synthesis of [ 894852-01-8 ]

* 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 [ 894852-01-8 ]

[ 894852-01-8 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 709652-78-8 ]
  • [ 894852-01-8 ]
  • (E)-3-(2,2-dimethyl-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-7-yl)-N-methyl-N-((3-methylbenzofuran-2-yl)methyl)acrylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
46% With N-ethyl-N,N-diisopropylamine;palladium diacetate; tris-(o-tolyl)phosphine; In N,N-dimethyl-formamide; propiononitrile;Heating / reflux; b) (E)-3 -(2,2-Dimethyl-3 -oxo-3 ,4-dihydro-2H-pyrido[3,2-&] [ 1 ,4]oxazin-7-yl)-iV-methyl-N- (3-methylbenzofuran-2-yhnethyl)acrylamide; A solution of N-methyl-N-(3-methylbenzofuran-2-yhnethyl)acrylamide (0.231 g,1.01 mmol) in propionitrile (4 mL) and DMF (0.8 mL) was deoxygenated with Ar for 20 min. The solution was treated with diisopropylethylamine (0.28 mL, 1.64 mmol) and 7- bromo-2,2-dimethyl-4H-rhoyrido[3,2-][l,4]oxazin-3-one (0.200 g, 0.775 mmol). The solution was deoxygenated with Ar for 20 min. Pd(OAc)2 (0.017 g, 0.078 mmol) and P(o- tol)3 (0.047 g, 0.15 mmol) were then added and the solution was deoxygenated again with Ar for 10 min. The mixture was heated to reflux for 18 h, then allowed to cool. The mixture was diluted with H2O (100 mL). The resulting solids were collected by filtration <n="132"/>and washed with Et2O (50 mL). Residual palladium was removed by silica gel plug (silica gel, 95:5, CH2Cl2/Me0H) the resulting solution concentrated to reveal a light orange solid. The solid was triturated with Et2O and dried to give the title compound (0.14 g, 46%) as a light pink solid and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-J
  • 2
  • [ 59154-46-0 ]
  • [ 39903-01-0 ]
  • [ 894852-01-8 ]
YieldReaction ConditionsOperation in experiment
84% With potassium carbonate; In acetone; for 18h;Heating / reflux; a) 7-Bromo-2,2-dimethyl-4H-pyrido[3,2-] [ 1 ,4]oxazin-3 -one; To a mixture of 2-amino-5-bromopyridin-3-ol (0.500 g, 2.64 mmol) and K2CO3 (1.09 g, 7.93 mmol) in acetone (11.0 niL) was added ethyl bromoisobutyrate (0.50 mL, 3.4 mmol). The solution was stirred under N2 for 18 h and then heated to reflux. After 18 h, the solution was cooled and concentrated. The light-pink, sweet-smelling solid was dissolved in CH2Cl2 (50 mL) and MeOH (5 mL). The solution was diluted with H2O (150 mL) and then washed with CH2Cl2 (3 x 75 mL). The combined organic layers were washed with brine (2 x 100 mL), dried (Na2SO4) and concentrated to yield the title compound (0.57 g, 84percent) as an off-white solid: 1H NMR (300 MHz, DMSO-J,*) delta 11.39 (s, IH), 8.03 (d, J=1.2 Hz, IH), 7.66 (d, 0.9 Hz, IH), 1.43 (s, 6H).
  • 3
  • [ 894852-01-8 ]
  • [ 894852-03-0 ]
YieldReaction ConditionsOperation in experiment
76% a) 7-Bromo-2,2-dimethyl-3,4-dihydro-2H-pyrido[3,2-][l,4]oxazine; To a solution of 7-bromo-2,2-dimethyl-4H-pyrido[3,2-][l,4]oxazin-3-one (0.360 g, 1.39 mmol) in TetaF (8.9 mL) at 0 0C was added BH3 (8.43 mL of a 1.0 M solution in THF, 8.43 mmol). The solution was heated to reflux. After 18 h, the solution was cooled to 0 0C and the reaction quenched with MeOH (15 mL). The mixture was concentrated and the resulting off-white solid was dissolved in MeOH (15 mL) and NaOH (10 mL of a 1 N solution). The mixture was heated at reflux to 4 h. The MeOH was removed under reduced pressure. The resulting precipitate was collected by filtration and washed with H2O (10 mL). The white solid was dried to give the title compound (0.260 g, 76%) as white needles: 1H NMR (300 MHz, DMSO-^) delta 7.62 (d, J= 2.1 Hz, IH), 7.10 (d, J = 1.5 Hz, IH), 7.03(br s, IH), 3.14 (d, J= 2.4 Hz, 2H), 1.25 (s, 6H); MS (ESI) m/e 243 (M + H)+.
  • 4
  • [ 894852-01-8 ]
  • [ 941604-85-9 ]
YieldReaction ConditionsOperation in experiment
65% A dichloroethane (10 mL) solution of 7-bromo-2,2-dimethyl-2H-pyrido[3,2-b][l,4]oxazin-3(4H)-one(930 rag, 3.6 mmol) and phosphorus pentachloride (1518 mg, 7.8 mmol) was irradiated in a microwave oven for 10 min at 160 0C. The solution was cooled to -78 0C and NH3 gas was condensed over it. The mixture was slowly let to warm to 21 0C, diluted with CH2Cl2, washed with dilute solution of NaOH, dried and evaporated. Crystallization from CH2Cl2/hexane afforded 602 mg (65%) of the title compound. 1HNMR (300 MHz, CDCl3, delta) 8.06 (d, J=2.0 Hz, IH), 7.24 (d, J=2.0 Hz, IH), 3.73 (s, IH), 1.53 (s, 6H). MS (ESI) m/e 256 (M + H)+.
  • 5
  • [ 600-00-0 ]
  • [ 894852-01-8 ]
YieldReaction ConditionsOperation in experiment
To a suspension of sodium hydride (60% dispersion in mineral oil, 0.68 g) in N,N-dimethylformamide (15 mL) was added dropwise a solution of 2-amino- 5- bromopyridin-3-ol (3.22 g) in N,N-dimethylformamide (25 mL) at room temperature over a period of 10 minutes, and the mixture was stirred at room temperature for 20 minutes. To the mixture was added dropwise ethyl alpha-bromoisobutyrate (3.32 g) over a period of 20 minutes, and the reaction mixture was stirred at room temperature for 1 hour and at 80 C for 2 hours. After cooling, to the reaction mixture was added cold water, and the mixture was extracted with ethyl acetate. The organic layer was washed successively water and brine, dried over magnesium sulfate and concentrated in vacuo by a half volume. The precipitates were collected by filtration to give 7-bromo-2,2- dimethyl-2H-pyrido[3,2-b][l,4]oxazin- 3(4H)-one (0.90 g) was obtained as a powder. MS(APCI) m/z: 257/279 [M+H]+
  • 6
  • [ 16867-03-1 ]
  • [ 894852-01-8 ]
  • 7
  • [ 20348-21-4 ]
  • [ 894852-01-8 ]
YieldReaction ConditionsOperation in experiment
86% With bromine; sodium carbonate; In dichloromethane; at 0 - 35℃; for 16h; Step-(ii): Synthesis of 7-bromo-2.2-dimethyl-2H-pyridor3.2-biri.41oxazin-3(4H)-one (Intermediate- 18) To a stirred solution of 2,2-dimethyl-2H-pyrido[3,2-b][l ,4]oxazin-3(4H)-one (18.1) (2 g, 11.23 mmol) in DCM (20 mL) was added Na2C03 (3.57 g, 33.70 mmol) followed by bromine (0.92 mL, 17.97 mmol) at 0C and the reaction mixture was allowed to stir at 20- 35C for 16 h. Then the reaction mixture was diluted with ice water, obtained solid was filtered and washed with water to get the desired compound as a white solid (1.8 g, 86%); lU NMR (400MHz, DMSO-<) delta 11.39 (s, 1H), 8.04 (d, J=.9 Hz, 1H), 7.66 (d, /=1.4 Hz, 1H), 1.43 (s, 6H); LC-MS: 257.0 (M+l)+.
 

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Technical Information

Categories

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[ 894852-01-8 ]

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