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Structure of 864076-05-1

Chemical Structure| 864076-05-1

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Product Details of [ 864076-05-1 ]

CAS No. :864076-05-1
Formula : C6H7BrN2O2
M.W : 219.04
SMILES Code : O=C(C1=NC(Br)=CN1C)OC
MDL No. :MFCD13189816
InChI Key :ROEZBNMDDJUDSC-UHFFFAOYSA-N
Pubchem ID :53302209

Safety of [ 864076-05-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 864076-05-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 5
Fraction Csp3 0.33
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 42.47
TPSA ?

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

44.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.12
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

1.22
Log Po/w (WLOGP)?

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

0.97
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.

0.36
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

0.87
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.11

Water Solubility

Log S (ESOL):?

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

-2.17
Solubility 1.48 mg/ml ; 0.00675 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.

-1.74
Solubility 3.95 mg/ml ; 0.018 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

-1.73
Solubility 4.05 mg/ml ; 0.0185 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.

-6.77 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<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)

2.22

Application In Synthesis of [ 864076-05-1 ]

* 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 [ 864076-05-1 ]

[ 864076-05-1 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 67-56-1 ]
  • [ 30148-23-3 ]
  • [ 864076-05-1 ]
YieldReaction ConditionsOperation in experiment
15.6% Step 2To a stirred solution of 2,2,2-trichloro-l-(l-methyl-lH-imidazol-2-yl)ethanone (12.42 g, 54.6 mmol) in THF (40 mL) at -10 0C was added n-bromosuccinimide (6.95 ml, 81.9 mmol). The reaction mixturewas kept at -10 0C for 2 h, warmed to RT with stirring for 12 h and concentrated. The residue was purified with ISCO using straight DCM. The solid obtained was dissolved in MeOH (40 mL), 60percent NaH (80 mg) was added and the reaction mixture heated to 75 0C for 1 h. The reaction mixturewas concentrated and the residue purified with ISCO using 0-10percent EtOAc in DCM to give methyl 4-bromo-l-methyl-lH-imidazole-2- carboxylate (1.86 g, 15.6percent yield).
  • 3
  • [ 864076-05-1 ]
  • [ 1413063-58-7 ]
YieldReaction ConditionsOperation in experiment
100% With ammonia; In methanol; at 20℃; for 16h; To the saturated solution of ammonia in MeOH was added 165 mg of <strong>[864076-05-1]4-bromo-1-methyl-1H-imidazole-2-carboxylic acid methyl ester</strong> and the resulting mixture was stirred at 20° C. for 16 h. The solution was evaporated to give 4-bromo-1-methyl-1H-imidazole-2-carboxylic acid amide (154 mg, yield 100percent). LC-MS calcd for C5H6BrN3O (m/e) 202.97, obsd 204 and 206 [M+1]+.
  • 4
  • [ 1313196-09-6 ]
  • [ 124-41-4 ]
  • [ 864076-05-1 ]
YieldReaction ConditionsOperation in experiment
81% A suspension of 1-(4-bromo-l-methyl-1H-imidazol-2-yl)-2,2,2-trichloroethanone (0.266 g, 868 muiotaetaomicron, Eq: 1) in methanol (1.11 g, 1.41 ml, 34.7 mmol, Eq: 40) was heated to reflux for 3 hours then at room temperature overnight. To the reaction mixture, sodium methoxide (15.6 mg, 16.1 mu, 86.8 muiotaetaomicron, Eq: 0.1) was added and stirring was continued at room temperature for 3 hours. The reaction mixture was concentrated in vacuo. The residue was purified by chromatography on silica gel to afford the desired product as a light brown solid (155 mg, 81 percent). MS (m/z) = 219.1, 221.1 [(M+H)+].
68% In methanol; at 25℃; for 0.333333h; To the solution of 1.18 g of 1-(-4-bromo-1-methyl-1H-imidazol-2-yl)-2,2,2-trichloroethanone in 10 mL of methanol was added 42 mg of sodium methoxide and the resulting mixture was stirred at 25° C. for 20 min. TLC showed completion of the reaction. The solution was evaporated, redissolved in 30 mL of DCM, washed with water (15 mL.x.2) and brine (15 mL). The solution was dried over anhydrous sodium sulfate and filtered. The residue was purified by silica gel column (DCM/MeOH=60/1) to give 4-bromo-1-methyl-1H-imidazole-2-carboxylic acid methyl ester (0.575 g, yield 68percent). 1H NMR (300 MHz, CDCl3) delta 7.02 (s, 1H), 4.00 (s, 3H). 3.93 (s, 3H). LC-MS calcd for C6H7BrN2O2 (m/e) 217.97, obsd 219 and 221 [M+1]+
  • 5
  • [ 864076-05-1 ]
  • (3R)-3-hydroxy-1-methyl-3-[2-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethynyl]pyrrolidin-2-one [ No CAS ]
  • (R)-methyl 4-(3-((3-hydroxy-1-methyl-2-oxopyrrolidin-3-yl)ethynyl)phenyl)-1-methyl-1H-imidazole-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
42.7% With bis-triphenylphosphine-palladium(II) chloride; cesium fluoride; In ethanol; water; at 100℃; for 0.75h;Microwave irradiation; A solution of (3^)-3-hydroxy-l-methyl-3-[2-[3-(4,4,5,5-tetramethyl-l ,3,2- dioxaborolan-2-yl)phenyl]ethynyl]pyrrolidin-2-one (73 mg., 0.21 mmol), methyl 4-bromo-l- methyl-lh-imidazole-2-carboxylate (40 mg, 0.18 mmol), cesium fluoride (54 mg, 0.36 mmol) and bis(triphenylphosphine)palladium(II) dichloride (12.5 mg, 0.018 mmol) in ethanol (1.5 mL) and water (1.0 mL) was degassed. The reaction mixture was heated in microwave at 100 °C for 45 min. The reaction was filtered through celite. The crude product was purified by flash chromatography (MeOH/DCM) then submitted for rHPLC to give product (27 mg, 42.7percent). LC-MS (ES, m/z): 354 [M+H]+.
  • 6
  • [ 67-56-1 ]
  • [ 1313196-09-6 ]
  • [ 864076-05-1 ]
YieldReaction ConditionsOperation in experiment
96% With dmap; at 20℃; for 0.5h; A solution of SI-2 (1.91 g, 6.24 mmol) and DMAP (305 mg, 2.50 mmol) in MeOH (31 mL) was stirred for 30min at room temperature. The reaction mixture was evaporated and the obtained residue was purified by silica gel column chromatography (SiO2, EtOAc) to give the desired product 6a (1.32 g, 96percent yield) as white solid.
96% With dmap; at 25℃; for 0.5h; A solution of the compound 2-4 (1.91 g, 6.24 mmol) and DMAP (305 mg, 2.50 mmol) in MeOH (31 mL) was stirred at room temperature for 30 minutes. The reaction mixed liquid was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (SiO2, EtOAc), so as to provide the target compound 2-5 (1.32 g, 96percent yield) as a white solid substance. Melting point (Mp.) 94-95° C.; 1H NMR (400 MHz, CDCl3) delta 3.94 (s, 3H), 4.01 (s, 3H), 7.03 (s, 1H); 13C NMR (100 MHz, CDCl3) delta 36.0, 52.4, 115.6, 125.7, 135.9, 158.6; IR (ATR) nu 1713, 1446, 1243, 1122, 953 cm?1; HRMS ((+)-ESI-TOF) m/z: [M+H]+ Calcd. for C6H8BrN2O2+ 218.9764; Found 218.9749.
  • 7
  • [ 864076-05-1 ]
  • methylamine hydrochloride salt [ No CAS ]
  • 4-bromo-N,1-dimethyl-1H-imidazole-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
To a suspension of methylamine hydrochloride (78.6 mg, 1.16 mmol, Eq: 3) in dioxane (3.88 ml) was added dropwise 2 M trimethylaluminum in toluene (582 mu, 1.16 mmol, Eq: 3) (slight gas evolution) and the mixture was stirred for 30 minutes at room temperature. Then methyl 4- bromo-1 -methyl-1H-imidazole-2-carboxylate (0.085 g, 388 muiotaetaomicron, Eq: 1) was added and the mixture was heated to reflux overnight. The reaction mixture was quenched with 120 ul of water (strong gas evolution) and the mixture was stirred for 15 minutes at room temperature. Then sodium sulfate was added and the stirring was continued for 1 hour. The suspension was filtered and washed with dichloromethane and dichloromethane/methanol 9: 1. The obtained solution was concentrated in vacuo. The residue was purified by chromatography on silica gel to afford the desired product as a white solid (51 mg, 60 percent). MS (m/z) = 218.1, 220.1 [(M+H)+].
  • 8
  • [ 864076-05-1 ]
  • S-(trifluoromethyl)dimesitylsulfanium triflate [ No CAS ]
  • methyl 1-methyl-4-(trifluoromethyl)-1H-imidazole-2-carboxylate [ No CAS ]
 

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