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Chemical Structure| 7499-66-3 Chemical Structure| 7499-66-3

Structure of 7499-66-3

Chemical Structure| 7499-66-3

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Product Details of [ 7499-66-3 ]

CAS No. :7499-66-3
Formula : C10H8BrN
M.W : 222.08
SMILES Code : NC1=CC=C2C=C(Br)C=CC2=C1
MDL No. :MFCD01026466
InChI Key :UBLKHAWYJFEPDX-UHFFFAOYSA-N
Pubchem ID :348404

Safety of [ 7499-66-3 ]

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

Computational Chemistry of [ 7499-66-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 10
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 0.0
Num. H-bond donors 1.0
Molar Refractivity 56.05
TPSA ?

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

26.02 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.01
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

2.97
Log Po/w (WLOGP)?

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

3.19
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.

3.24
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

2.92
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.87

Water Solubility

Log S (ESOL):?

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

-3.7
Solubility 0.0438 mg/ml ; 0.000197 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.

-3.18
Solubility 0.147 mg/ml ; 0.000661 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

-4.57
Solubility 0.00594 mg/ml ; 0.0000267 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

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

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

No
Log Kp (skin permeation)?

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

-5.55 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

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<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)

1.16

Application In Synthesis of [ 7499-66-3 ]

* 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 [ 7499-66-3 ]

[ 7499-66-3 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 15231-91-1 ]
  • [ 7499-66-3 ]
YieldReaction ConditionsOperation in experiment
94% With ammonium bisulfite; ammonia; water; at 150℃; for 48h; 6-bromonaphthalen-2-amine (15)6-Bromonaphthalen-2-ol (1.5 g, 6.7 mmol) was heated with ammonium hydroxide (10ml) and ammonium sulfite (3.5 g, 26 mmol) in a seal tube at 150 0C for 48 h. After cooling to room temperature, ethyl acetate was added and organic layer was separated, washed with brine, dried over anhydrous sodium sulfate and evaporated to obtain crude product 15 (1.4 g, Y; 94 %), which was pure enough and can be used directly for next step without further purification. 1H NMR (CDCl3): delta 7.84 (IH, br), 7.56 (IH, d, J= 9.6 Hz), 7.43 (2H, m), 6.95 (2H, m), 3.87 (2H, b). Leigh C. Anderson and Donald G. Thomas: Quinoidation of Triaryl Compounds - Hydroxynaphthyldiphenylcarbinols J. Am. Chem. Soc; 65; 1943; 239, 241.
33% With ammonium bisulfite; ammonia; In water; at 190℃; for 24h; Preparation of 6-Bromonaphthalen-2-amine (9) 6-Bromo-2-naphthol (2.0 g, 9 mmol), ammonium sulfite (10.4 g, 90 mmol) and 10 mL of ammonia solution were sealed in a tube. The reaction mixture was heated at 190 C. for 24 hrs and allowed to cool to room temperature, the reaction mixture was extracted with EtOAc. HCl (10%) was added to the organic layer to give a precipitate. After filtration, the solid was dissolved in 10% of Na2CO3 and extracted with EtOAc, the organic layer was dried over Na2SO4. The solvent was removed under reduced pressure to give the product as yellow solid (0.67 g, 33%). MS [M++43]=265, LC-MS: tR=20.14 min.
21% With ammonium hydroxide; ammonium sulfite monohydrate; In water; at 120℃; for 17h; General procedure: Ammonium hydroxide aqueous solution ( 841mg, 27.8 mmol, 2 equiv.) was added to a freshly prepared aqueous solution of ammonium sulfite monohydrate (3.2 g, 27.8 mmol, 2 equiv.) in a 35 ml high pressure reaction vessel. Appropriate 2-naphthol analog (1a or 1b) (13.9 mmol, 1 equiv.) was added, and the mixture was stirred for 17 h at 120 C. The reaction mixture was filtered and the precipitate was washed with cold 5% aq. NaOH and then dissolved in DCM. The organic layer was again washed with 5% aq. NaOH (3×30 mL) and dried over anh. sodium sulfate to afford 2-naphthylamines after the removal of solvent in vacuo.
  • 2
  • [ 1780-26-3 ]
  • [ 7499-66-3 ]
  • [ 856975-58-1 ]
  • <i>N</i>4,<i>N</i>6-bis-(6-bromo-[2]naphthyl)-2-methyl-pyrimidine-4,6-diyldiamine [ No CAS ]
  • 3
  • [ 759396-95-7 ]
  • [ 7499-66-3 ]
  • [ 71590-31-3 ]
  • <i>N</i>4-(6-bromo-[2]naphthyl)-<i>N</i>2-(2-diethylamino-ethyl)-6-methyl-pyrimidine-2,4-diyldiamine; dihydrochloride [ No CAS ]
  • 4
  • [ 759396-95-7 ]
  • [ 7499-66-3 ]
  • <i>N</i>4-(6-bromo-[2]naphthyl)-<i>N</i>2-(2-diethylamino-ethyl)-6-methyl-pyrimidine-2,4-diyldiamine; dihydrochloride [ No CAS ]
  • 5
  • [ 67878-77-7 ]
  • [ 7499-66-3 ]
  • 6
  • [ 7499-66-3 ]
  • [ 82-23-5 ]
  • 2-bromo-14<i>H</i>-benzo[<i>a</i>]naphth[2,3-<i>h</i>]acridine-5,8,13-trione [ No CAS ]
  • 7
  • [ 7499-66-3 ]
  • [ 67878-77-7 ]
  • 8
  • [ 7499-66-3 ]
  • [ 13720-06-4 ]
  • 9
  • [ 7499-66-3 ]
  • [ 91065-17-7 ]
  • 10
  • [ 7499-66-3 ]
  • 3,10-dibromo-dibenzo[<i>a,h</i>]phenazine [ No CAS ]
  • 11
  • [ 7499-66-3 ]
  • [ 389806-32-0 ]
YieldReaction ConditionsOperation in experiment
51.1% To a 500 mL round bottom containing a stir bar was added borontrifluoride diethyletherate (14.5 mL, 115 mmol) and the flask was cooled to -30 °C. Compound CXI-1 (6.0 g, 27.3 mmol) dissolved in THF (75 mL) was added dropwise. 90percent tert-butylnitrite (12 mL, 100 mmol) was dissolved in THF (75 mL) and added dropwise. The reaction was allowed to warm to -5 °C at which time 100 mL of diethyl ether was added and the mixture was allowed to stir at -5 °C for 10 min until a pale solid precipitated. The solid was filtered and washed with ether to afford a pale solid which was then added in one portion to a 500 mL round bottom containing a stir bar, potassium iodide (6.4 g, 38.7 mmol), iodine (4.92 g, 19.4 mmol), and acetonitrile (100 mL). The reaction was allowed to stir at room temperature for 15 mins. 150 mL of a saturated aqueous solution of sodium thiosulfate was added as well as 150 mL of DCM. The mixture was allowed to stir for 5 mins, the layers were separated, the organics were dried using anhydrous MgS04, and the solvent was removed in vacuo. The residue was purified by column (PE) to give compounf CXI-2 (4.6 g, yield 51.1percent).
  • 12
  • [ 7499-66-3 ]
  • [ 861032-76-0 ]
  • <i>N</i>4-(6-bromo-[2]naphthyl)-<i>N</i>2-(3-diethylamino-propyl)-6-methyl-pyrimidine-2,4-diyldiamine [ No CAS ]
  • 15
  • [ 677291-27-9 ]
  • [ 7499-66-3 ]
  • 16
  • [ 7499-66-3 ]
  • [ 108-24-7 ]
  • [ 71590-32-4 ]
YieldReaction ConditionsOperation in experiment
With triethylamine;dmap; In dichloromethane; at 0 - 25℃; for 3h; To a solution of aminobromonaphthlene (1.81 g, 8.2 mmol) in 80 mL of dichloromethane at 0 0C were added acetic anhydride (1.15 mL, 12.2 mmol), and tpiethylamine (2.86 mL, 20 mmol) and a small amount of DMAP. The solution was warmed to RT and stirred for 3 h. The solvent was removed and the residue was dissolved in ethyl acetate, washed with water, 1N HCl, water, 1N NaOH, saturated sodium bicarbonate solution and brine successively. The organic layer was then dried with sodium sulfate and concentrated m vacuo to give the acetamide as a pmk solid. This bromide intermediate was subjected to the same Heck reaction and hydrogenation procedures as descnbed earlier, and shown in Scheme 25, to provide the product as a sticky oil. To a solution of this intermediate (86 mg, 0.22 mmol) in 15 mL of chloroform at 0 0C, was added dropwise a solution of bromine (14 uL, 42 mg, 0.26 mmol) in 1.5 mL of chloroform. The mixture was stirred at 0 0C for 5 mm and quenched with 1percent sodium sulfite. Two batches of this intermediate were combined and the aqueous phase was extracted with chloroform three times. The organic phase was washed with saturated sodium bicarbonate solution, and dried over sodium sulfate. A mixture of this bromide intermediate (0.56 g, 1.19 mmol), methyl boronic acid (93 mg, 1.55 mmol), potassium carbonate (494 mg, 3.58 mmol), palladium tetrakistriphenylphosphme (138 mg, 0.12 mmol), 2 mL of water and 20 mL of dioxane, was degassed with argon and heated at 100 0C overnight. After concentration, the residue was pupified by Biotage to give a white solid. To a solution of this methylated intermediate (89 mg, 0.22 mmol) in 5 mL of chloroform, were added potassium acetate (44 mg, 0.44 mmol), acetic acid (26 mg, 0.44 mmol), acetic anhydpide (45 mg, 0.44 mmol), 18- crown-6 (10 mg), and amylnitrite (74 uL, 0 63 mmol) The mixture was heated at 700C overnight. The reaction mixture was then purified by Biotage to give a white solid. To a suspension of this tricyclic acetamide intermediate (58 mg, 0.14 mmol) in 40 mL of methanol, were added sodium ethoxide (226 uL, 21percent in methanol). After 5 mm, to the mixture was added 10 mL of aqueous 1N lithium hydroxide solution, and the mixture was stirred for 30 mm The solvent was evaporated and the aqueous residue was acidified and extracted with 30percent isopropanol in chloroform. After removing the solvent, the residue was purified by RP-HPLC to give the desired product as a white solid 1H NMR (DMSO-d6, 500 MHz) delta 11.2 (1H, s), 8.55 (1H, s), 8.47 (1H, d), 8 24 (1H, d), 7.95 (1H, d), 7.84 (1H, s), 7 67 (1H, d), 7 59 (3H, m), 7.12 (1H, t), 3.12 (2H, t), 2.83 (2H, t); LCMS m/z 360 (M++1).
  • 17
  • [ 7499-66-3 ]
  • [ 703-61-7 ]
  • (6-bromo-[2]naphthyl)-(4-chloro-[2]quinolyl)-amine [ No CAS ]
  • 18
  • [ 7499-66-3 ]
  • [ 56-81-5 ]
  • [ 99585-68-9 ]
  • 21
  • [ 7499-66-3 ]
  • [ 77-78-1 ]
  • [ 5043-03-8 ]
  • 22
  • [ 15231-91-1 ]
  • [ 7664-41-7 ]
  • 4>2SO3 [ No CAS ]
  • [ 7499-66-3 ]
YieldReaction ConditionsOperation in experiment
99% Step 2. The above-prepared compound was dissolved in 20 mL DMF. To it was added 10 mL water. The mixture was refluxed overnight. It was diluted with 500 mL EtOAc, washed with brine (*2), dried, concentrated in vacuuo to afford 6-bromo-2-naphthylamine (1.2 g, 99percent). Rf 0.73 (1:1 EtOAc:hexane), ES-MS: (M+H)+222, 224 (Br pattern).
  • 24
  • [ 13720-04-2 ]
  • [ 10034-85-2 ]
  • [ 64-19-7 ]
  • [ 7499-66-3 ]
  • 25
  • [ 7647-01-0 ]
  • [ 13720-04-2 ]
  • copper (I)-chloride [ No CAS ]
  • [ 7499-66-3 ]
  • 26
  • [ 7647-01-0 ]
  • [ 13720-04-2 ]
  • tin (II)-chloride [ No CAS ]
  • [ 7499-66-3 ]
  • 27
  • [ 7647-01-0 ]
  • [ 13720-04-2 ]
  • tin [ No CAS ]
  • [ 7499-66-3 ]
  • 28
  • [ 7499-66-3 ]
  • 4-methoxycarbonylmethoxy-benzoic acid 4,6-dimethoxy-[1,3,5]triazin-2-yl ester [ No CAS ]
  • [ 170737-27-6 ]
  • 29
  • [ 7499-66-3 ]
  • [ 324-41-4 ]
YieldReaction ConditionsOperation in experiment
With pyridine hydrogenfluoride; sodium nitrite; at 85℃; for 4h; Commercially available 6-bromo-2-aminonaphthalene (100 mg, 0.45 mmol) in 4 mL of HF-pyridine was treated with sodium nitrite (101 mg, 1.35 mmol), aged to a thickly turbid mixture after 2 h, heated m a sealed tube at 85 0C for 2 h, the mixture cooled, and partitioned between chloroform and water. The organic phase was separated and concentrated in vacuo to provide the clean 6-bromo-2- fluoronaphthalene product. EXAMPLE 18 was prepared from this 6-bromo-2-fluoronaphthalene intermediate in a manner similar to EXAMPLE 17 above and illustrated in Scheme 5. The desired product was purified via preparative RPHPLC. 1H NMR (CD3OD, 600 MHz) delta 8.54 (d, 1H), 8 05 (dd, 1H), 7.81 (dd, 1H), 7.66-7.38 (m, 2H), 7.54 (dt, 1H), 7.46-7.44 (m, 2H), 7.24 (dt, 1H), 7 12 (t, 1H), 3.20 (t, 2H), 2.83 (t, 2H); LCMS m/z 338 (M++1).
  • 30
  • [ 7499-66-3 ]
  • (6‐bromonaphthalen‐2‐yl)hydrazine hydrochloride [ No CAS ]
  • 32
  • [ 628-21-7 ]
  • [ 7499-66-3 ]
  • [ 136924-72-6 ]
  • 33
  • [ 7499-66-3 ]
  • [ 109-70-6 ]
  • [ 922528-39-0 ]
  • 34
  • [ 7499-66-3 ]
  • [ 922528-40-3 ]
  • 35
  • [ 7499-66-3 ]
  • [ 922528-45-8 ]
 

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