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Chemical Structure| 606-00-8 Chemical Structure| 606-00-8

Structure of 606-00-8

Chemical Structure| 606-00-8

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Product Details of [ 606-00-8 ]

CAS No. :606-00-8
Formula : C8H7Br2NO2
M.W : 308.96
SMILES Code : O=C(OC)C1=CC(Br)=CC(Br)=C1N
MDL No. :MFCD00010873
InChI Key :NGXVMFCGYYHEGC-UHFFFAOYSA-N
Pubchem ID :69069

Safety of [ 606-00-8 ]

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

Computational Chemistry of [ 606-00-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 2
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 57.53
TPSA ?

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

52.32 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.33
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

3.03
Log Po/w (WLOGP)?

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

2.59
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.

2.77
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

2.35
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.61

Water Solubility

Log S (ESOL):?

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

-3.87
Solubility 0.0413 mg/ml ; 0.000134 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.

-3.79
Solubility 0.0496 mg/ml ; 0.000161 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

-3.8
Solubility 0.0485 mg/ml ; 0.000157 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

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

No
Log Kp (skin permeation)?

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

-6.03 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

1.0 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)

1.63

Application In Synthesis of [ 606-00-8 ]

* 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 [ 606-00-8 ]

[ 606-00-8 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 82-44-0 ]
  • [ 606-00-8 ]
  • 3,5-dibromo-2-(9,10-dioxo-9,10-dihydro-[1]anthrylamino)-benzoic acid methyl ester [ No CAS ]
  • 4
  • [ 134-20-3 ]
  • [ 606-00-8 ]
YieldReaction ConditionsOperation in experiment
99% With bromine; sodium hydrogensulfite; In dichloromethane; acetic acid; EXAMPLE B Preparation of Methyl 3,5-Dibromoanthranilate {Formula II: X=Br, R=CO2 CH3, R3 =R4 =H} A solution of methyl anthranilate (28.70 g, 189.9 mmol) in acetic acid (150 mL) was cooled with an ice bath. Bromine (64.83 g, 405.6 mmol) was added slowly dropwise over 50 min. (A considerable amount of insoluble white solid was formed during the bromine addition.) The solution was then removed from the ice bath and stirred at room temperature for 2 hr. The reaction mixture was dissolved in CH2 Cl2 (500 mL was required to dissolve the white solid) and the orange solution was washed with a solution of sodium bisulfite giving a pale yellow solution. The organic phase was washed twice with water (250 mL each) and with saturated brine (250 mL). After drying over sodium sulfate, the solvent was removed giving methyl 3,5-dibromoanthranilate (58.10 g, 99 percent) as a pale yellow solid. The product was recrystallized from methanol (300 mL), giving white needles (52.78 g, mp 87.5-88.5 C.). 1 H NMR (CDCl3) delta7.95 (d, J=2.1 Hz, 1H), 7.66 (d, J=2.4 Hz, 1H), 6.34 (br s, 2H), 3.88 (s, 3H): 13 C NMR (CDCl3) delta166.9, 146.6, 139.0, 133.0, 112.6, 111.1, 106.5, 52.1: MS (70 eV) 309, 277, 249, 224, 170, 63.
96% In a 100 L double-layer glass reactor, 26.50 kg of dichloromethane, 8.0 kg of purified water, and 3.02 kg of methyl 2-aminobenzoate were successively added, and the mixture was uniformly stirred.A solution of bromine (3.83 kg) in dichloromethane (5.3 kg) was slowly added to the reaction mixture obtained above at normal temperature.After the addition was completed, stirring was continued for 10 minutes, and 2.50 kg of a 30% hydrogen peroxide solution was slowly added to the reaction solution, and the mixture was stirred for 6 hours, and the reaction was completed.To the reaction solution, slowly add 3.5 kg of a 20% sodium sulfite solution to quench the reaction, phase separate, and extract the organic phase with 8.0 kg of purified water.The aqueous phase was extracted twice with dichloromethane, and the organic phases were combined.The residue was transferred to a 100 L autoclave and 15.0 kg of methanol was added, heated to dissolve, and stirred for 15 minutes.The reaction solution was transferred to a crystallizing tank, and slowly cooled to room temperature at rest, and then placed in a refrigerator and further cooled to 0 C for 2 hours.The solid was filtered and dried at 50 C. After the water was passed, the yield was 5.88 kg, and the yield was 96%.
95% To a round bottom flask was added CuBr2 (33 mmol, 7.40 g), EtOH (250 mL) and 14a (66 mmol, 10.00 g). The mixture was stirred at 35C for 2 h. Then, another portion of CuBr2 (33 mmol, 7.40 g) was added, and the mixture was continuously stirred for 1 h at 35C before being heated at reflux. After the completion of the reaction, the mixture was cooled to room temperature, and the solvent was removed under reduced pressure. To the residue was added ammonia hydroxide (170 mL, 25% w/v) with vigorous stirring. After being stirred for 3 h at room temperature, the mixture was filtered and washed with ammonia hydroxide (5 mL ×3) and water (20 mL ×5). The filter cake was recrystallized with MeOH (25 mL) to produce 14bb in 95% yield as white solid. Methyl 2-amino-3,5-dibromobenzoate (14bb) White solid, mp 89.9-91.6 C, 95% yield. 1H NMR (CDCl3) delta 8.00 (d, J = 2.1 Hz, 1H), 7.71 (d, J = 2.1 Hz, 1H), 6.38 (s, 2H), 3.91 (s, 3H). 13C NMR (CDCl3) delta 167.0, 146.6, 139.1, 133.1, 112.6, 111.1, 106.5, 52.2. MS (ESI): m/z calcd for C8H8Br2NO2: 307.9 [M+H]+; found: 308.1 (79Br, 79Br, 30%), 310.1 (79Br, 81Br 100%), 312.1 (81Br, 81Br 30%).
  • 6
  • [ 109-97-7 ]
  • [ 606-00-8 ]
  • 2-(2'-Amino-3',5'-dibrombenzoyl)-1H-pyrrol [ No CAS ]
  • 7
  • [ 77-78-1 ]
  • [ 609-85-8 ]
  • [ 606-00-8 ]
  • [ 146273-81-6 ]
  • 8
  • [ 134-20-3 ]
  • [ 606-00-8 ]
  • [ 104670-74-8 ]
  • [ 52727-57-8 ]
  • 9
  • [ 85-44-9 ]
  • [ 606-00-8 ]
  • 3,5-dibromo-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-benzoic acid methyl ester [ No CAS ]
  • 10
  • [ 606-00-8 ]
  • C8H5Br2N2O2(1+)*BF4(1-) [ No CAS ]
  • 11
  • [ 553-90-2 ]
  • [ 606-00-8 ]
  • [ 1049106-45-7 ]
  • 13
  • [ 606-00-8 ]
  • 2-[3-(3,5-dibromo-2-methylamino-benzylamino)-propylamino]-1<i>H</i>-quinolin-4-one [ No CAS ]
  • 14
  • [ 606-00-8 ]
  • [ 51329-15-8 ]
YieldReaction ConditionsOperation in experiment
67% With tetrahydrofuran; tert.-butylnitrite; dimethyl sulfoxide; at 30℃; for 1h;Green chemistry; General procedure: A solution of amine 2 (5 mmol) in THF (3 mL) was added dropwise over 20 min to a solution of t-BuONO (7.5 mmol) and DMSO (0.5 mmol) in THF (7 mL) at 30 C. The mixture was stirred at 30 C until the starting materials 2 were consumed (monitored by TLC). The solvent was evaporated, and the yields of the low boiling point products were determined by GC; the high boiling point products were isolated by column chromatography on silica gel (hexane/ethyl acetate).
  • 15
  • [ 606-00-8 ]
  • [ 439940-37-1 ]
  • 16
  • [ 606-00-8 ]
  • [ 439940-36-0 ]
  • 17
  • [ 606-00-8 ]
  • [ 439940-38-2 ]
  • 18
  • [ 606-00-8 ]
  • [ 439940-35-9 ]
  • 19
  • [ 606-00-8 ]
  • C78H80 [ No CAS ]
  • 20
  • [ 606-00-8 ]
  • 9,10-Bis-((E)-2-{3,5-bis-[(E)-2-(4-tert-butyl-phenyl)-vinyl]-phenyl}-vinyl)-anthracene [ No CAS ]
  • 21
  • [ 606-00-8 ]
  • 3,4,5-Tribrom-2-(2'-amino-3',5'-dibrombenzoyl)-1H-pyrrol [ No CAS ]
  • 22
  • [ 606-00-8 ]
  • 10,12-dibromo-13<i>H</i>-naphth[2,3-<i>c</i>]acridine-5,8,14-trione [ No CAS ]
  • 23
  • [ 186581-53-3 ]
  • [ 609-85-8 ]
  • [ 606-00-8 ]
  • 24
  • [ 25145-43-1 ]
  • [ 606-00-8 ]
  • [ 883244-37-9 ]
  • 25
  • [ 606-00-8 ]
  • methyl 3,5-bis-[2-(4-tert-butylphenyl)vinyl]benzoate [ No CAS ]
  • 26
  • [ 606-00-8 ]
  • 3,5-bis-[2-(4-tert-butylphenyl)vinyl]benzaldehyde [ No CAS ]
  • 27
  • [ 606-00-8 ]
  • 1,3-bis-[2-(4-tert-butylphenyl)vinyl]-5-vinylbenzene [ No CAS ]
  • 28
  • [ 606-00-8 ]
  • C69H73N [ No CAS ]
  • 29
  • [ 606-00-8 ]
  • {3,5-bis-[2-(4-tert-butylphenyl)vinyl]phenyl}methanol [ No CAS ]
  • 30
  • 3-Aethinyl-1,5-diphenyl-penta-1,4-diin-3-ol [ No CAS ]
  • [ 606-00-8 ]
  • methyl (E)-3,5-dibromo-2-(2-methyl-5-phenyl-3-styryl-1H-pyrrol-1-yl)benzoate [ No CAS ]
  • 31
  • [ 606-00-8 ]
  • 6,8-dibromo-1H-benzo[d][1,3]oxazin-2(4H)-one [ No CAS ]
  • 32
  • [ 606-00-8 ]
  • [ 50739-76-9 ]
YieldReaction ConditionsOperation in experiment
95% With potassium borohydride; ethanol; at 20 - 40℃; for 0.5h;Industrial scale; 10.0 kg of absolute ethanol and 5.88 kg of methyl 3,5-dibromo-2-aminobenzoate were added to a 100 L double-layer glass reactor.After stirring uniformly, 2.62 kg of potassium borohydride was added, and stirring was continued for 30 minutes at room temperature.The temperature of the reaction mixture was raised to 40 C, and 13.5 g of an anhydrous ethanol solution containing 2.7 kg of calcium chloride was slowly added to the reaction liquid for a period of not less than 6 hours.After the addition, the reaction was stirred for 8 hours, and the UPLC test was taken. After the reaction was passed (the methyl 3,5-dibromo-2-aminobenzoate was not more than 1.0%), and cooled to room temperature.The temperature of the reaction solution was maintained at not more than 35 C, and 32 kg of 5% hydrochloric acid was slowly added to the reaction solution to adjust the pH to 2 to 3, and stirring was continued for 20 minutes, and the pH was measured again.Centrifugally filter, rinse the filter cake with purified water to neutrality, and transfer the obtained solid to the reaction kettle.20 kg of a 0.4% sodium hydroxide solution was added, and the mixture was heated to 45 C and stirred for 15 minutes, and then cooled to room temperature.Centrifugal filtration, rinse the filter cake with purified water to neutrality. It is placed in a blast drying oven tray, dried at 60 C for 20 hours, and after receiving water, it is charged with 5.08 kg, and the yield is 95%.
  • 33
  • [ 942-24-5 ]
  • [ 606-00-8 ]
  • methyl 2,4-dibromo-12-oxo-5,12-dihydroindolo[2,1-b]quinazoline-6-carboxylate [ No CAS ]
  • 34
  • [ 606-00-8 ]
  • 6,8-dibromo-2-(3-phenyl-1H-pyrazol-4-yl)-2,3-dihydroquinazolin-4(1H)-one [ No CAS ]
  • 35
  • [ 606-00-8 ]
  • [ 16524-04-2 ]
YieldReaction ConditionsOperation in experiment
With ammonium hydroxide; at 100℃; for 12h;Sealed tube; General procedure: The syntheses of compounds 3a-3x were mainly referred to literature method [35]. A mixture of 1a-1q, 1w, 1x (2mmol), EDC?HCl (575mg, 3mmol), HOBt (446mg, 3.3mmol), NH4Cl (348mg, 6.5mmol) and DIPEA (2.3mL, 13mmol) in DMSO (7mL) was stirred at room temperature for 15h. The mixture was extracted with EtOAc three times, and the combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford 3a-3q, 3w, 3x. A mixture of 2r-2v (2mmol) and NH3·H2O (25-28wt%, 80mmol) in sealed tube was heated at 100C for 12h. The mixture was cooled to room temperature and extracted with EtOAc three times. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford 3r-3v.
 

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