146533-41-7|5-(4-Bromophenyl)-4,6-dichloropyrimidine| Ambeed

Size	Price	VIP Price	US Stock	Global Stock	In Stock
{[ item.pr_size ]}		Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

{[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

Quality Control of [ 146533-41-7 ] Purity: 97% SDS Specification

COA

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

NMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

CNMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

HPLC

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

LC-MS

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

1-2 Day Shipping
High Quality
Technical Support

Product Details of [ 146533-41-7 ]

CAS No. :	146533-41-7
Formula :	C₁₀H₅BrCl₂N₂
M.W :	303.97
SMILES Code :	ClC1=C(C2=CC=C(Br)C=C2)C(Cl)=NC=N1
MDL No. :	MFCD13151897
InChI Key :	WEEFLZORZXLIJE-UHFFFAOYSA-N
Pubchem ID :	19735262

Safety of [ 146533-41-7 ]

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

Computational Chemistry of [ 146533-41-7 ] 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	2.0
Num. H-bond donors	0.0
Molar Refractivity	65.19
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	25.78 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.64
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	4.44
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	4.21
Log P_o/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.	3.1
Log P_o/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	4.38
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	3.75

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-5.05
Solubility	0.00272 mg/ml ; 0.00000896 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-4.7
Solubility	0.00607 mg/ml ; 0.00002 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately 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	-6.24
Solubility	0.000175 mg/ml ; 0.000000574 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Poorly 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.	-5.0 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)	1.96

Application In Synthesis of [ 146533-41-7 ]

* 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 [ 146533-41-7 ]

[ 146533-41-7 ] Synthesis Path-Downstream 1~35

1
[ 706811-25-8 ]
[ 146533-41-7 ]

Yield	Reaction Conditions	Operation 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).

References: [1]Patent: CN108997223,2018,A .Location in patent: Paragraph 0056; 0063; 0065; 0070; 0077; 0084; 0091.
[2]Journal of Medicinal Chemistry,2012,vol. 55,p. 7849 - 7861.
[3]Monatshefte fur Chemie,2018,vol. 149,p. 653 - 661.
[4]Bioorganic and Medicinal Chemistry,2007,vol. 15,p. 1586 - 1605.
[5]Patent: WO2004/50640,2004,A1 .Location in patent: Page 31.
[6]Patent: WO2009/24906,2009,A1 .Location in patent: Page/Page column 13-14.
[7]Patent: WO2006/51502,2006,A2 .Location in patent: Page/Page column 19.
[8]Patent: US2012/142716,2012,A1 .Location in patent: Page/Page column 5.
[9]Patent: WO2017/93903,2017,A1 .Location in patent: Page/Page column 20.
[10]Patent: CN109081814,2018,A .Location in patent: Paragraph 0013; 0022; 0027; 0032.

2
[ 146533-41-7 ]
[ 17573-94-3 ]
[ 926008-69-7 ]

References: [1]Bioorganic and Medicinal Chemistry,2007,vol. 15,p. 1586 - 1605.

3
[ 146533-41-7 ]
5-(4-bromophenyl)-6-(4-dimethylaminophenylethynyl)pyrimidin-4-ylamine [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2007,vol. 15,p. 1586 - 1605.

4
[ 14062-25-0 ]
[ 146533-41-7 ]

References: [1]Bioorganic and Medicinal Chemistry,2007,vol. 15,p. 1586 - 1605.

5
[ 93139-85-6 ]
[ 146533-41-7 ]

References: [1]Bioorganic and Medicinal Chemistry,2007,vol. 15,p. 1586 - 1605.

6
[ 1878-68-8 ]
[ 146533-41-7 ]

References: [1]Bioorganic and Medicinal Chemistry,2007,vol. 15,p. 1586 - 1605.
[2]Patent: US2012/142716,2012,A1 .
[3]Journal of Medicinal Chemistry,2012,vol. 55,p. 7849 - 7861.
[4]Patent: WO2017/93903,2017,A1 .
[5]Monatshefte fur Chemie,2018,vol. 149,p. 653 - 661.
[6]Patent: CN108997223,2018,A .

7
[ 146533-41-7 ]
2-methoxyethanesulfamic acid amide potassium salt [ No CAS ]
[ 706811-26-9 ]

Yield	Reaction Conditions	Operation in experiment
	In DMF (N,N-dimethyl-formamide); at 20℃; for 24h;	A solution of 4, 6-DICHLORO-5- (4-BROMOPHENYL)-PYRIMIDINE 1.79 mg) and 2- methoxyethanesulfamic acid amide potassium salt (4.54 g, Example 1) in DMF (25 ml) was stirred at rt for 24 h before bulk of the solvent was removed in vacuo. The residue was treated with 10% aq. citric acid. The suspension was filtered, and the mother liquor was extracted twice with EA. The organic phase was evaporated and combined with the solid material collected earlier. The crude product was purified by column chromatography on silica gel eluting with DCM containing 4% of methanol to give 2-METHOXYETHANESULFAMIC acid [6-CHLORO-5- (4-BROMOPHENYL)- pyrimidin-4-yl]-amide (640 mg) as a beige foam. LC-MS2 : TR = 4.46 min, [M+1] + = 422.93, [M-1]-= 420.82.

References: [1]Patent: WO2004/50640,2004,A1 .Location in patent: Page 32.

8
[ 146533-40-6 ]
[ 146533-41-7 ]

Yield	Reaction Conditions	Operation in experiment
	With trichlorophosphate;	In analogy to Example 3, paragraph b), from 5-(p-bromophenyl)-4,6(1H,5H)-pyrimidinedione and POCl3, there was prepared 5-(p-bromophenyl)-4,6-dichloropyrimidine, melting point 99-100 C. (from hexane), and therefrom with p-chlorophenylsulfonamide, there was prepared N-[5-(p-bromophenyl)-6-chloro-4-pyrimidinyl]-p-chlorobenzenesulfonamide, melting point 266-268 C. (from CH3 CN).

References: [1]Patent: US5270313,1993,A .

9
[ 146533-41-7 ]
3-benzyloxypropylsulfamide potassium salt [ No CAS ]
[ 887366-72-5 ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide; at 20℃; for 18h;	f) A solution of <strong>[146533-41-7]4,6-dichloro-5-(4-bromophenyl)-pyrimidine</strong> (405 mg, 1.33 mmol) and 3-benzyloxypropylsulfamide potassium (752 mg, 2.66 mmol) in DMSO is stirred at rt under argon for 18 h. The clear solution is poured onto 10% aq. citric acid solution (50 mL) and extracted twice with EA (2x75 mL). The organic extracts are washed with water (50 mL) and the solvent is evaporated. The residue is purified by column chromatography on silica gel eluting with hexane/EA 3:2 to afford 1-benzyloxypropanesulfamic acid [6-chloro-5-(4-bromophenyl)-pyrimidin-4- yl]-amide (524 mg) as a colourless foam. LC-MS: tR = 1.05 min, [M+H]+ = 510.96; 1H NMR (CDCI3): delta 8.44 (s, 1H), 7.71-7.65 (m, 2H), 7.40-7.28 (m, 5H), 7.18-7.12 (m, 2H), 6.90 (s, 1H), 6.05 (t, J = 5.9 Hz, 1 H), 4.49 (s, 2H), 3.57 (t, J 0 5.9 Hz, 2H), 3.18 (q, J = 5.9 Hz, 2H), 1.88 (p, J = 5.9 Hz, 2H).

References: [1]Patent: WO2006/51502,2006,A2 .Location in patent: Page/Page column 20.

10
[ 146533-41-7 ]
benzylsulfamide potassium salt [ No CAS ]
[ 441797-42-8 ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide; at 20℃; for 24h;	A solution of 5-(4-bromophenyl)-4,6-dichloro-pyrimidine (4.0O g, 13.2 mmol) and benzylsulfamide potassium salt (7.38 g, 32.9 mmol) in DMSO (30 mL) was stirred at rt for 24 h before being diluted with a 10% aq. citric acid solution (200 mL). The suspension that formed was filtered. The collected solid was washed well with water and dried under HV at 400C for 48 h to give the expected product as a white powder (6.15 g). 1H NMR (CDCl3): delta 4.23 (d, J = 5.9 Hz, 2H); 5.94 (t br., J = 6 Hz, IH); 7.05 (d, J = 8.2 Hz, 2H); 7.20-7.35 (m, 5H); 7.68 (d, J = 8.2 Hz, 2H); 8.61 (s, IH). LC-MS: tR = 1.02 min, [M+H]+ = 452.95.

References: [1]Patent: WO2009/24906,2009,A1 .Location in patent: Page/Page column 13.

11
[ 41841-16-1 ]
[ 146533-41-7 ]

References: [1]Patent: US2012/142716,2012,A1 .
[2]Journal of Medicinal Chemistry,2012,vol. 55,p. 7849 - 7861.
[3]Patent: WO2017/93903,2017,A1 .
[4]Monatshefte fur Chemie,2018,vol. 149,p. 653 - 661.
[5]Patent: CN108997223,2018,A .

12
[ 146533-41-7 ]
[ 441796-08-3 ]

References: [1]Patent: US2012/142716,2012,A1 .

13
[ 146533-41-7 ]
[ 441796-09-4 ]

References: [1]Patent: US2012/142716,2012,A1 .
[2]Patent: WO2015/121397,2015,A1 .

14
[ 146533-41-7 ]
[ 1103522-45-7 ]

References: [1]Patent: US2012/142716,2012,A1 .
[2]Patent: WO2015/121397,2015,A1 .
[3]Patent: WO2015/121397,2015,A1 .

15
[ 146533-41-7 ]
benzylsulfamide potassium salt [ No CAS ]
[ 441797-42-8 ]

Yield	Reaction Conditions	Operation in experiment
		A solution of 5-(4-bromophenyl)-4,6-dichloro-pyrimidine (4.00 g, 13.2 mmol) and benzylsulfamide potassium salt (7.38 g, 32.9 mmol) in DMSO (30 mL) was stirred at it for 24 h before being diluted with a 10% aq. citric acid solution (200 mL). The suspension that formed was filtered. The collected solid was washed well with water and dried under HV at 40 C. for 48 h to give the expected product as a white powder (6.15 g).1H NMR (CDCl3): delta 4.23 (d, J=5.9 Hz, 2H); 5.94 (t br., J=6 Hz, 1H); 7.05 (d, J=8.2 Hz, 2H); 7.20-7.35 (m, 5H); 7.68 (d, J=8.2 Hz, 2H); 8.61 (s, 1H).LC-MS: tR=1.02 min, [M+H]+=452.95.

References: [1]Patent: US2012/142716,2012,A1 .Location in patent: Page/Page column 5.

16
[ 149506-35-4 ]
[ 146533-41-7 ]

17
[ 146533-41-7 ]
C₄H₁₀NO₂S^(1-)*K⁽¹⁺⁾ [ No CAS ]
C₁₄H₁₅BrClN₃O₂S [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 7849 - 7861.

18
[ 146533-41-7 ]
C₈H₁₁N₂O₂S^(1-)*K⁽¹⁺⁾ [ No CAS ]
C₁₈H₁₆BrClN₄O₂S [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 7849 - 7861.

19
[ 146533-41-7 ]
C₄H₉N₂O₃S^(1-)*K⁽¹⁺⁾ [ No CAS ]
C₁₄H₁₄BrClN₄O₃S [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 7849 - 7861.

20
[ 146533-41-7 ]
potassium (N-propylsulfamoyl)amide [ No CAS ]
[ 1393813-42-7 ]

Yield	Reaction Conditions	Operation in experiment
110 g	With sodium amide; In dimethyl sulfoxide; at 25 - 30℃; for 10h;Inert atmosphere;	To a solution of 5-(4-bromophenyl)-4,6-dichloro-pyrimidine (100 g) in dimethyl sulfoxide (700 ml), potassium(N-propylsulfamoyl)amide (145 g) was added at 25-30C under nitrogen atmosphere and stirred for 10 hrs. After reaction completion, pH of the reaction mass was adjusted to 2-3 using aqueous hydrochloric acid at 25-30C and stirred for 75 mins. The solid obtained was filtered, washed with water and suck dried under vacuum. Methanol (3500 ml) was added to the above compound and heated to reflux temperature then stirred for an hour at reflux. The reaction mass was distilled upto 450-550 mL remained in the flask. The reaction mass was cooled to 25-30C, stirred for 75 mins then further cooled to 0- 5C and stirred for 75 mins. The obtained solid was filtered, washed with methanol and dried under vacuum at 50-55C for 4 hrs to get the title compound. Yield: 110 g; Purity by HPLC: 99.10%

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 7849 - 7861.
[2]Patent: WO2017/93903,2017,A1 .Location in patent: Page/Page column 21.

21
[ 146533-41-7 ]
[ 1393813-43-8 ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 7849 - 7861.
[2]Patent: WO2016/203489,2016,A1 .
[3]Patent: WO2017/33016,2017,A1 .
[4]Patent: WO2017/93903,2017,A1 .
[5]Patent: WO2017/191565,2017,A1 .
[6]Monatshefte fur Chemie,2018,vol. 149,p. 653 - 661.

22
[ 146533-41-7 ]
C₁₃H₁₅BrN₄O₄S [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 7849 - 7861.

23
[ 146533-41-7 ]
[ 441796-12-9 ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 7849 - 7861.

24
[ 146533-41-7 ]
C₁₆H₂₁BrN₄O₄S [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 7849 - 7861.

25
[ 146533-41-7 ]
[ 441797-01-9 ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 7849 - 7861.

26
[ 146533-41-7 ]
C₂₀H₂₁BrN₄O₄S [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 7849 - 7861.

27
[ 146533-41-7 ]
C₁₆H₁₉BrN₄O₅S [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 7849 - 7861.

28
[ 146533-41-7 ]
C₁₅H₁₈BrN₃O₄S [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 7849 - 7861.

29
[ 146533-41-7 ]
C₁₆H₂₀BrN₃O₄S [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 7849 - 7861.
[2]Journal of Medicinal Chemistry,2012,vol. 55,p. 7849 - 7861.

30
[ 146533-41-7 ]
macitentan [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 7849 - 7861.
[2]Patent: WO2015/121397,2015,A1 .
[3]Patent: WO2015/121397,2015,A1 .
[4]Patent: WO2016/203489,2016,A1 .
[5]Patent: WO2016/203489,2016,A1 .
[6]Patent: WO2017/33016,2017,A1 .
[7]Patent: WO2017/93903,2017,A1 .
[8]Patent: WO2017/191565,2017,A1 .
[9]Monatshefte fur Chemie,2018,vol. 149,p. 653 - 661.

31
[ 146533-41-7 ]
[ 441798-25-0 ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 7849 - 7861.

32
[ 146533-41-7 ]
[ 441796-13-0 ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 7849 - 7861.

33
[ 146533-41-7 ]
[ 441798-39-6 ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 7849 - 7861.

34
[ 146533-41-7 ]
[ 441797-02-0 ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 7849 - 7861.

35
[ 146533-41-7 ]
[ 1393813-60-9 ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 7849 - 7861.

Historical Records

Technical Information

• Alkyl Halide Occurrence • Benzylic Oxidation • Birch Reduction • Blanc Chloromethylation • Friedel-Crafts Reaction • General Reactivity • Grignard Reaction • Hiyama Cross-Coupling Reaction • Hydrogenolysis of Benzyl Ether • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Preparation of Alkylbenzene • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reactions of Dihalides • Stille Coupling • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Vilsmeier-Haack Reaction

Related Functional Groups of
[ 146533-41-7 ]

Aryls

A109973 [3974-16-1]

4,6-Dichloro-5-phenylpyrimidine

Similarity: 0.87

A101072 [160377-42-4]

5-(4-Bromophenyl)pyrimidine

Similarity: 0.68

A363645 [1245646-55-2]

(4,6-Dichloropyrimidin-5-yl)(4-methoxyphenyl)methanone

Similarity: 0.62

A376628 [654655-68-2]

3-Benzyl-6-bromo-2-chloroquinoline

Similarity: 0.62

A316260 [10177-06-7]

2,6-Dichloro-5-phenylnicotinonitrile

Similarity: 0.60

Bromides

A103667 [573675-55-5]

7-Bromo-4-chloroquinazoline

Similarity: 0.75

A131150 [1260847-61-7]

7-Bromo-4,6-dichloroquinazoline

Similarity: 0.72

A837791 [959237-68-4]

7-Bromo-2,4-dichloroquinazoline

Similarity: 0.71

A112852 [205055-63-6]

6-Bromo-1-chloroisoquinoline

Similarity: 0.71

A381350 [34551-41-2]

5-Bromo-1-chloroisoquinoline

Similarity: 0.69

Chlorides

A109973 [3974-16-1]

4,6-Dichloro-5-phenylpyrimidine

Similarity: 0.87

A165773 [16019-31-1]

5-Allyl-4,6-dichloropyrimidine

Similarity: 0.76

A103667 [573675-55-5]

7-Bromo-4-chloroquinazoline

Similarity: 0.75

A131150 [1260847-61-7]

7-Bromo-4,6-dichloroquinazoline

Similarity: 0.72

A837791 [959237-68-4]

7-Bromo-2,4-dichloroquinazoline

Similarity: 0.71

Related Parent Nucleus of
[ 146533-41-7 ]

Pyrimidines

A109973 [3974-16-1]

4,6-Dichloro-5-phenylpyrimidine

Similarity: 0.87

A165773 [16019-31-1]

5-Allyl-4,6-dichloropyrimidine

Similarity: 0.76

A161316 [16019-33-3]

2-(4,6-Dichloropyrimidin-5-yl)acetaldehyde

Similarity: 0.71

A260719 [1780-38-7]

2,4,6-Trichloro-5-ethylpyrimidine

Similarity: 0.69

A172845 [6343-68-6]

4,6-Dichloro-5-ethylpyrimidin-2-amine

Similarity: 0.69

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

{[proInfo.proName]}

CAS No.: 146533-41-7

{[proInfo.proName]}

CAS No.: 146533-41-7

Alternative Products

Product Details of [ 146533-41-7 ]

Safety of [ 146533-41-7 ]

Computational Chemistry of [ 146533-41-7 ] Show Less

Physicochemical Properties

Lipophilicity

Water Solubility

Pharmacokinetics

Druglikeness

Medicinal Chemistry

Application In Synthesis of [ 146533-41-7 ]

[ 146533-41-7 ] Synthesis Path-Downstream 1~35

Related Products

Historical Records

Technical Information

Categories

Related Functional Groups of
[ 146533-41-7 ]

Aryls

Bromides

Chlorides

Related Parent Nucleus of
[ 146533-41-7 ]

Pyrimidines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Molarity Calculator

Total Compounds Calculator

Dissolution Calculator

{[proInfo.proName]}

CAS No.: 146533-41-7

{[proInfo.proName]}

CAS No.: 146533-41-7

Alternative Products

Product Details of [ 146533-41-7 ]

Safety of [ 146533-41-7 ]

Computational Chemistry of [ 146533-41-7 ] Show Less

Physicochemical Properties

Lipophilicity

Water Solubility

Pharmacokinetics

Druglikeness

Medicinal Chemistry

Application In Synthesis of [ 146533-41-7 ]

[ 146533-41-7 ] Synthesis Path-Downstream 1~35

Related Products

Historical Records

Technical Information

Categories

Related Functional Groups of [ 146533-41-7 ]

Aryls

Bromides

Chlorides

Related Parent Nucleus of [ 146533-41-7 ]

Pyrimidines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Molarity Calculator

Total Compounds Calculator

Dissolution Calculator

Related Functional Groups of
[ 146533-41-7 ]

Related Parent Nucleus of
[ 146533-41-7 ]