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Product Details of [ 706811-25-8 ]

CAS No. :706811-25-8
Formula : C10H7BrN2O2
M.W : 267.08
SMILES Code : OC1=NC=NC(O)=C1C2=CC=C(Br)C=C2
MDL No. :MFCD13151898
InChI Key :PIUMVXYVNAISNG-UHFFFAOYSA-N
Pubchem ID :54191439

Safety of [ 706811-25-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 706811-25-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 12
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 4.0
Num. H-bond donors 2.0
Molar Refractivity 59.21
TPSA ?

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

66.24 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.0
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

2.48
Log Po/w (WLOGP)?

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

2.32
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.

1.64
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

2.14
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.12

Water Solubility

Log S (ESOL):?

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

-3.58
Solubility 0.0696 mg/ml ; 0.00026 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.

-3.52
Solubility 0.0815 mg/ml ; 0.000305 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

-3.87
Solubility 0.0358 mg/ml ; 0.000134 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.

-6.17 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)

1.94

Application In Synthesis of [ 706811-25-8 ]

* 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 [ 706811-25-8 ]

[ 706811-25-8 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 706811-25-8 ]
  • [ 146533-41-7 ]
YieldReaction ConditionsOperation in experiment
86% With trichlorophosphate; In water; N,N-dimethyl-aniline; toluene; at 30 - 100℃; for 5h; 200 g of the intermediate 3 obtained in the third step was taken in a 3 L three-necked flask.Add 300g of toluene and 180g of N,N-dimethylaniline, mechanically stirred,230 g of phosphorus oxychloride was added dropwise at 30 C, and the temperature was raised to 55 C after the addition.After the solid is completely dissolved, the temperature is raised to 100 C, the reaction is carried out for 4 h, and then cooled to 25 C for use.450 g of water was mixed with 500 g of toluene, and cooled to 25 C with stirring.The above-mentioned alternate reaction solution was added, and the process control temperature was 30 C.Stir at 30 C for 1 h, then stand for stratification, and extract the aqueous phase with toluene several times.The toluene extract and the organic phase are combined, and the combined organic phases are decomposed under reduced pressure.Further, ethanol was added, and the mixture was stirred at 15 C for 1.5 hours, suction filtered, and dried.The product 5-(4-bromophenyl)-4,6-dichloropyrimidine 195.6 g, the yield was 86.0%,The liquid chromatographic test results of the obtained product are shown in Figure 2.HPLC purity is 99.93%,The test results came to the Waters 2489-1525 high performance liquid chromatograph produced by Waters.
79% With trichlorophosphate; at 90℃; A stirred solution of 100 g 5-(4-bromophenyl)pyrimidine-4,6-diol (11, 0.374 mol) was added to 300 cm3 phosphorousoxy chloride. The reaction mass was heated to 90 Cand maintained until completion (monitored by HPLC).After completion of the reaction, the reaction mass wascooled to 10-15 C and quenched over water below 15 C.The obtained solid was filtered and washed with water until the pH of the filtrate became 6.5-7.0. The material was dried under reduced pressure at 65 C to obtain the crudesolid. The crude solid was further recrystallized in methanol and the obtained solid was filtered and dried toprovide 2. Yield: 90 g (79%); purity by HPLC: 99.7%;m.p.: 100-103 C. The spectral data of compound 2 werefound to agree with the reported data [8].
With N,N-dimethyl-aniline; trichlorophosphate; at 130℃; for 2h; To a suspension of 5- (4-BROMOPHENYL)-PYRIMIDINE-4, 6-DIOL (9.90 G) in POCI3 (130 ml) was carefully added N, N-dimethylaniline (13.5 ML). The mixture was heated to 130C for 2 h. The dark brown solution was evaporated and the residue was poured into ice/water. The suspension was diluted with 2 N HCI and water and stirred for 20 min. The precipitate was collected and washed with water. The solid material was dissolved in EA, washed with 1 N aq. HCI and brine. The organic phase was dried over MGS04 and evaporated. The material was further purified by column chromatography on silica gel eluting with hexane: EA 95: 5 to 1: 1 followed by CRYSTALLISATION from hexane/EA AT-20C to give 4, 6-DICHLORO-5- (4- bromophenyl)-pyrimidine (8.3 g) as pale YELLOW CRYSTALS.'H-NMR (D6-DMSO) : 7.39-7. 44 (m, 2H), 7.72-7. 76 (m, 2H), 8.94 (s, 1 H).
With N,N-dimethyl-aniline; trichlorophosphate; at 130℃; for 2h; To a suspension of 5-(4-bromophenyl)-pyrimidine-4,6-diol (9.9O g) in POCl3 (13O mL) was carefully added JV,lambda/-dimethylaniline (13.5 mL). The mixture is heated to 1300C for 2 h. The dark brown solution is concentrated in vacuo and the residue was poured into ice/water. The suspension is diluted with 2 N HCl and water and stirred for 20 min. The precipitate that formed is collected and washed with water. The solid material is dissolved in EA, washed with 1 N aq. HCl and brine. The org. phase is dried over MgSO4 and evaporated. The material is further purified by column chromatography on silica gel eluting with Hex:EA 95:5 to 1 :1 followed by crystallisation from Hex/EA at -200C to give 4,6-dichloro-5-(4-bromophenyl)-pyrimidine as pale yellow crystals (8.3 g). 1H-NMR(D6-DMSO): delta 7.39-7.44 (m, 2H), 1.12-1.16 (m, 2H), 8.94 (s, IH).
With N,N-dimethyl-aniline; trichlorophosphate; at 130℃; for 2h; d) To a suspension of 5-(4-bromophenyl)-pyrimidine-4,6-diol (9.90 g) in POCI3 (130 ml_) is carefully added N, N-dimethylaniline (13.5 ml_). The mixture is heated to 1300C for 2 h. The dark brown solution is evaporated and the residue is poured into ice/water. The suspension is diluted with 2 N HCI and water and stirred for 20 min. The precipitate is collected and washed with water. The solid material is dissolved in EA, washed with 1 N aq. HCI and brine. The organic phase is dried over MgSO4 and evaporated. The material is further purified by column chromatography on silica gel eluting with hexane:EA 95:5 to 1 :1 followed by crystallisation from hexane/EA at -200C to give 4,6-dichloro-5-(4-bromophenyl)- pyrimidine (8.3 g) as pale yellow crystals. 1H-NMR(D6-DMSO): 7.39-7.44(m, 2H)1 7.72-7.76(m, 2H), 8.94(s, 1 H).
To a suspension of 5-(4-bromophenyl)-pyrimidine-4,6-diol (9.90 g) in POCl3 (130 mL) was carefully added N,N-dimethylaniline (13.5 mL). The mixture is heated to 130 C. for 2 h. The dark brown solution is concentrated in vacuo and the residue was poured into ice/water. The suspension is diluted with 2 N HCl and water and stirred for 20 min. The precipitate that formed is collected and washed with water. The solid material is dissolved in EA, washed with 1 N aq. HCl and brine. The org. phase is dried over MgSO4 and evaporated. The material is further purified by column chromatography on silica gel eluting with Hex:EA 95:5 to 1:1 followed by crystallisation from Hex/EA at -20 C. to give 4,6-dichloro-5-(4-bromophenyl)-pyrimidine as pale yellow crystals (8.3 g).1H-NMR(D6-DMSO): delta 7.39-7.44 (m, 2H), 7.72-7.76 (m, 2H), 8.94 (s, 1H).LC-MS: tR=1.02 min.
100 g With triethylamine; trichlorophosphate; In acetonitrile; at 25 - 85℃; for 5h;Inert atmosphere; Triethyl amine (130 mL) was added to a mixture of 5-(4-bromophenyl)-pyrimidine-4,6-diol (100 g), phosphoryl chloride (400 mL) and acetonitrile (600 mL) at 25-35C under nitrogen atmosphere for a period of 60 mins. The reaction mass was heated to 80-85C and stirred for 4 hrs. The reaction mass was distilled off under vacuum at below 75C followed by stripped off with acetonitrile. The reaction mass was cooled to 10-15C, water (500 mL) was added and stirred for 30 mins. Aqueous hydrochloric acid (2N, 500 ml) was added to the reaction mass at 10-15C and stirred for 30 mins. The solid obtained was filtered, washed with water and dried under vacuum at 40-45C for 6 hrs to get the title compound. Yield: 100 g; purity by HPLC: 99.0%
With N,N-dimethyl-aniline; trichlorophosphate; at 70℃; for 4h; Add 5-(4-bromophenyl)-4,6-dihydroxypyrimidine to a washed, dry round bottom flask.70 parts of phosphorus oxychloride (new steam),Then, 1 part of N,N-dimethylaniline was added dropwise thereto.Slowly turn on the magnetic stirrer and stir at room temperature for 15 minutes.Warmed to 70 C in 1 h,The reaction was carried out at this temperature for 3 h.After the reaction was terminated, it was naturally cooled to 55 C, and excess phosphorus oxychloride was distilled off under reduced pressure.Add the remaining mixture to the ice water, the temperature is controlled below 10 C, the natural yellow solid will be precipitated, and the pH of the solution will be adjusted.To be weakly acidic, it was washed twice with ice water and then with dichloroethane three times. After drying the wet product, a pale yellow product can be obtained (5-(4-Bromophenyl)-4,6-dichloropyrimidine).

 

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Technical Information

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