62224-16-2|Methyl 4-bromothiophene-2-carboxylate| Ambeed

Structure of 62224-16-2

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Quality Control of [ 62224-16-2 ] Purity: 98% SDS Specification

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Product Details of [ 62224-16-2 ]

CAS No. :	62224-16-2
Formula :	C₆H₅BrO₂S
M.W :	221.07
SMILES Code :	COC(=O)C1=CC(Br)=CS1
MDL No. :	MFCD06203668
InChI Key :	HPZXLAIWCQLSAR-UHFFFAOYSA-N
Pubchem ID :	12752071

Safety of [ 62224-16-2 ]

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

Computational Chemistry of [ 62224-16-2 ] Show Less

Physicochemical Properties

Num. heavy atoms	10
Num. arom. heavy atoms	5
Fraction Csp3	0.17
Num. rotatable bonds	2
Num. H-bond acceptors	2.0
Num. H-bond donors	0.0
Molar Refractivity	43.3
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	54.54 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.31
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	2.48
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.3
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.	1.69
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	3.04
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.36

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.01
Solubility	0.216 mg/ml ; 0.000975 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.	-3.27
Solubility	0.119 mg/ml ; 0.000537 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	-2.6
Solubility	0.553 mg/ml ; 0.0025 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.	-5.89 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)	2.37

Application In Synthesis of [ 62224-16-2 ]

* 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 [ 62224-16-2 ]

[ 62224-16-2 ] Synthesis Path-Downstream 1~35

1
[ 67-56-1 ]
[ 62224-16-2 ]
[ 5118-05-8 ]

References: [1]Journal of Chemical Research, Miniprint,1981,p. 1801 - 1824.

2
[ 67-56-1 ]
[ 16694-18-1 ]
[ 62224-16-2 ]

Yield	Reaction Conditions	Operation in experiment
100%	With sulfuric acid; at 25 - 50℃; for 12h;	To a solution of 4-bromo-2-thiophenecarboxylic acid (4g, 19 mmol) in MeOH (100 ml.) was added H2SO4 (5 ml.) dropwise at 25 0C. The solution was stirred for 12 h at 50 0C and was poured into ice-H2O and the pH was adjusted to ~1 1 with aqueous NaOH. The aqueous phase was extracted several times with DCM and the combined organic fractions were dried over Na2SO4, concentrated and used directly (4.27g, quant.): LCMS (ES) m/z 222 (M+H)+.
100%	sulfuric acid; at 50℃;	Example 1; Preparation of Lambda/-{(1 S)-2-amino-1-[(3,4-difluorophenyl)methyl1ethyl}-4-(1 /-/-pyrazol-4-yl)-2- thiophenecarboxamide; a) methyl 4-bromo-2-thiophenecarboxylate; To a solution of 4-bromo-2-thiophenecarboxylic acid (7 g, 34 mmol) in MeOH (170 ml.) was added cone. H2SO4 (17 ml_). After heating to 50 0C for 12 h, the reaction solution was cooled to room temperature and diluted with CHCI3 (100 ml_). The CHCI3 solution was washed with cold aqueous NaHCO3, then 5N NaOH and dried over Na2SO4. Concentration under vacuum gave the title compound as a yellow oil (7.2 g, quant.): LCMS (ES) m/z 222 (M+H)+.
95%		To a dry flask under N2 with a stirbar was added 6 g (29.1 mmol) of 4- bromothiophene-2-carboxylic acid (as prepared in the previous step) and dry methanol (100 mL). The solution was cooled in an ice-salt bath for 15 min and 2.55 mL (34.9 mmol) of thionyl chloride was added over 15 min, keeping the temperature <-5o C. The reaction mixture was stirred on the ice-salt bath for an additional 15 min, then for 1 h at rt, and finally refluxed for 8 h under N2. The resulting solution was cooled and concentrated to 6.7 g of pale amber oil. This oil was passed through 150 g of silica WITH ~600 mL CH2C12 (discarded the first 120 mL which contained minor impurities and no ester). The solvent was removed in vacuo to afford 6.11 g (95% yield) of the title compound as a colorless solid, which was used in the next step without further purification.

91.4%	With thionyl chloride; for 6h;Reflux;	In 100ml single neck flask was added 4-bromo-2-thiophenecarboxylic acid 2.07g (10mmol), thionyl chloride 1.19g (10mmol) and absolute ethanol 25ml, refluxed, 6h After TLC showed the starting material is no longer remaining. The solvent was distilled off under reduced pressure, ice water was added, adjusting the pH with saturated sodium carbonate solution to 9 to 10, and extracted with ethyl acetate (40ml × 3), the combined organic phase was washed twice with saturated brine, dried over anhydrous MgSO 4, pale yellow oily liquid 2.02g, yield 91.4%.
90%	With sulfuric acid; for 10h;Heating / reflux;	Example 1 : Methyl 4-{6-[4-(2-piperidin-l-ylethoxy)phenyllpyrazolo[l,5-alpyrimdin-3-vUthiophene- 2-carboxylate; Step 1 : methyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)thiophene-2-carboxylate; 4-Bromothiophene-2-carboxylic acid (0.418 g, 2 mmol) was dissolved in methanol (1 mL), and concentrated sulfuric acid (0.039 g, 0.4 mmol) was added. The mixture was refluxed for 1O h, poured into water, and subjected to 3-fold extraction with ethyl acetate. The organic layer was washed with K2CO3- solution, concentrated, dried over MgSO4, filtered and evaporated to give methyl 4-bromothiophene-2- carboxylate, weight 0.4 g (90% yield).A flask containing PdCl2(dppf) (0.32 g, 0.43 mmol), dppf (0.24 g, 0.43 mmol), KOAc (4.23 g, 0.043 mol), and pinacolediborone (5.5 g, 0.021 mol) was flushed with argon, then a solution of the ester from the foregoing step (3.2 g, 0.014 mol) in dioxane (60 mL) was added. The mixture was stirred at 850C under argon atmosphere for 40 h. Water (5-fold excess) was added, and the mixture was subjected to 3-fold extraction with ethyl acetate. The organic layer was washed with brine, concentrated, dried over MgSO4, filtered, and evaporated to give the crude methyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)thiophene- 2-carboxylate (5.1 g, purity 85% according to 1H NMR data). This crude boronate was used without further purification.
	With sulfuric acid;Heating / reflux;	Step 2 4-Bromo-thiophene-2-carboxylic acid (12.85g), CH30H (360 mL) and H2SO4 (95-98%, 6mL) were refluxed overnight. The solution was basified and evaporated to remove the organic solvent. The residue was extracted with EtOAc. The organic layer was washed with water and brine, then dried over Na2SO4, evaporated to give the product the solvent gave the product 4-Bromo-thiophene-2-carboxylic acid methyl ester (13 g).
	With thionyl chloride; at -20℃; for 2.08333h;Reflux;	4-bromo-2-thiophenecarboxylic acid (3.0 g) was dissolved in anhydrous methanol (30 mL) and cooled to -20 C.Then, thionyl chloride (5.1 g) was slowly added dropwise to the above mixture.After stirring for 5 minutes, the temperature was raised to reflux and the reaction was carried out for 2 h.The reaction was quenched with water and extracted with EtOAc.The extract is washed with saturated brine.After drying, it was concentrated to give a crude material (yellow oil, 3.24 g).
	With thionyl chloride; for 6h;Reflux;	To a stirring solution of 4-bromo-2-thiophenecarboxylic acid (3g, 14.5mmol) in methanol (25mL) was added thionyl chloride (1.74g, 14.5mmol). Reaction mixture was heated to reflux and stirred for 6h. Upon completion, the residue was taken up in ice water (60mL). The pH was adjusted to 9-10 with saturated sodium carbonate solution. The aqueous phase was extracted with ethyl acetate (40mL×3). The combined organic phase was washed twice with saturated brine (20mL×2) and dried over anhydrous MgSO4. After filtering out MgSO4, the solvent of filtrate was removed in vacuo to afford crude product of title compound as a pale-yellow oil which was used for next step directly. Yield: 98%; 1H NMR (300MHz, CDCl3) delta: 7.69 (s, 1H), 7.45 (s, 1H), 3.90 (s, 3H). MS (m/z): [M+H]+ 221.0, 223.0.

References: [1]Patent: WO2008/98104,2008,A1 .Location in patent: Page/Page column 134.
[2]Patent: WO2010/93885,2010,A1 .Location in patent: Page/Page column 37-38.
[3]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 491 - 495.
[4]Patent: WO2003/99805,2003,A1 .Location in patent: Page 151.
[5]Patent: CN103408540,2016,B .Location in patent: Paragraph 0100; 0164; 0165.
[6]Patent: WO2007/85873,2007,A1 .Location in patent: Page/Page column 18.
[7]Journal of Medicinal Chemistry,1992,vol. 35,p. 1109 - 1116.
[8]Journal of Chemical Research, Miniprint,1981,p. 1801 - 1824.
[9]Patent: WO2005/40161,2005,A1 .Location in patent: Page/Page column 78.
[10]Patent: CN108341774,2018,A .Location in patent: Paragraph 0531-0534.
[11]European Journal of Medicinal Chemistry,2019,vol. 176,p. 248 - 267.

3
[ 62224-16-2 ]
[ 927-74-2 ]
[ 130073-85-7 ]

References: [1]Journal of Medicinal Chemistry,1992,vol. 35,p. 1109 - 1116.
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 6938 - 6959.

4
[ 67-56-1 ]
[ 58777-65-4 ]
[ 62224-16-2 ]

References: [1]Archiv der Pharmazie,1998,vol. 331,p. 405 - 411.

5
[ 62224-16-2 ]
[ 58621-39-9 ]
[ 219771-99-0 ]

References: [1]Archiv der Pharmazie,1998,vol. 331,p. 405 - 411.

7
[ 62224-16-2 ]
[ 544-92-3 ]
[ 67808-33-7 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 491 - 495.

8
[ 62224-16-2 ]
cyclohexylammonium acrylate [ No CAS ]
3-(5-methoxycarbonyl-3-thienyl)acrylic acid [ No CAS ]

References: [1]Chemical and pharmaceutical bulletin,2002,vol. 50,p. 656 - 660.

9
[ 62224-16-2 ]
[ 473933-09-4 ]

References: [1]Chemical and pharmaceutical bulletin,2002,vol. 50,p. 656 - 660.

10
[ 18791-75-8 ]
[ 62224-16-2 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 491 - 495.
[2]Journal of Medicinal Chemistry,1992,vol. 35,p. 1109 - 1116.

11
[ 62224-16-2 ]
[ 237384-70-2 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 491 - 495.

12
[ 62224-16-2 ]
[ 237384-71-3 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 491 - 495.

13
[ 62224-16-2 ]
4-(4-phenyl-thiazol-2-yl)-thiophene-2-carboxamidine [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2002,vol. 12,p. 491 - 495.

14
[ 16694-18-1 ]
[ 62224-16-2 ]

Yield	Reaction Conditions	Operation in experiment
98%	With sulfuric acid; In methanol; at 65℃; for 17h;	A few drops of concentrated sulphuric acid are added to a solution of 5.0 g of the compound obtained during Stage 1 of Preparation 1 in 25 ml of methanol. The reaction medium is stirred at 65 C. for 17 hours and is then concentrated under reduced pressure. The oily residue obtained is dissolved in ethyl acetate (200 ml), washed with water (3×100 ml), dried over sodium sulphate and then concentrated under reduced pressure in order to produce 5.24 g of the desired product. Yield: 98% 1H NMR (CDCl3) delta (ppm): 3.90 (s, 3H), 7.45 (s, 1H), 7.70 (s, 1H)
95%	With thionyl chloride; In methanol; dichloromethane;	b) Methyl 4-bromothiophene-2-carboxylate To a cooled (-20 C.) solution of 6.02 g (29.1 mmol) of 4-bromothiophene-2-carboxylic acid (as prepared in the previous step) in 100 mL of anhyd MeOH under nitrogen was added 2.55 mL (34.9 mmol) of thionyl chloride dropwise at a rate to keep the temperature below -5 C. (ca. 8-10 min). After stirring for 1 h at room temperature, the mixture was refluxed for 8 h, cooled, and concentrated in vacuo. The resulting 6.7 g of pale amber oil was passed through a 150 g pad of silica gel with ca. 600 mL of CH2Cl2 (discarding the first 120 mL which contained a minor impurity) to afford, after concentration in vacuo, the title compound as a colorless oil (6.11 g, 95%). 1H-NMR (300 MHz, CDCl3) delta7.69 (d, 1 H, J=1.5 Hz), 7.45 (d, 1 H, J=1.5 Hz), and 3.90 (s, 3 H).
95%	With thionyl chloride; In methanol; dichloromethane;	b) Methyl 4-bromothiophene-2-carboxylate To a cooled (-20 C.) solution of 6.02 g (29.1 mmol) of 4-bromothiophene-2-carboxylic acid (as prepared in the previous step) in 100 mL of anhyd MeOH under nitrogen was added 2.55 mL (34.9 mmol) of thionyl chloride dropwise at a rate to keep the temperature below -5 C. (ca. 8-10 min). After stirring for 1 h at room temperature, the mixture was refluxed for 8 h, cooled, and concentrated in vacuo. The resulting 6.7 g of pale amber oil was passed through a 150 g pad of silica gel with ca. 600 mL of CH2Cl2 (discarding the first 120 mL which contained a minor impurity) to afford, after concentration in vacuo the title compound as a colorless oil (6.11 g, 95%). 1H-NMR (300 MHz, CDCl3) delta 7.69 (d, 1H, J=1.5 Hz), 7.45 (d, 1H, J=1.5 Hz), and 3.90 (s, 3H).

95%

With thionyl chloride; In methanol; dichloromethane;

b 4-Bromothiophene-2-carboxylic acid Methyl Ester To a dry flask under N2 with a stirbar was added 6 g (29.1 mmol) of 4-bromothiophene-2-carboxylic acid (as prepared in the previous step) and dry methanol (100 mL). The solution was cooled in an ice-salt bath for 15 min and 2.55 mL (34.9 mmol) of thionyl chloride was added over 15 min, keeping the temperature <-5 C. The reaction mixture was stirred on the ice-salt bath for an additional 15 min, then for 1 h at rt, and finally refluxed for 8 h under N2. The resulting solution was cooled and concentrated to 6.7 g of pale amber oil. This oil was passed through 150 g of silica with ~600 mL CH2Cl2 (discarded the first 120 mL which contained minor impurities and no ester). The solvent was removed in vacuo to afford 6.11 g (95% yield) of the title compound as a colorless solid, which was used in the next step without further purification.

References: [1]Patent: US2004/72871,2004,A1 .Location in patent: Page/Page column 29.
[2]Patent: US2002/37915,2002,A1 .
[3]Patent: US6291514,2001,B1 .
[4]Patent: US2004/9995,2004,A1 .
[5]Archiv der Pharmazie,1998,vol. 331,p. 405 - 411.

15
[ 62224-16-2 ]
[ 77133-27-8 ]

References: [1]Journal of Chemical Research, Miniprint,1981,p. 1801 - 1824.

16
[ 62224-16-2 ]
[ 78645-52-0 ]

References: [1]Journal of Chemical Research, Miniprint,1981,p. 1801 - 1824.

17
[ 62224-16-2 ]
<4-Methoxy-5-<<(4-methoxy-2-thienyl)-amino>-carbonyl>-2-thienyl>-carbaminsaeure-(1,1-dimethylethyl)ester [ No CAS ]

References: [1]Journal of Chemical Research, Miniprint,1981,p. 1801 - 1824.

18
[ 6324-10-3 ]
[ 62224-16-2 ]

References: [1]Journal of Chemical Research, Miniprint,1981,p. 1801 - 1824.

19
[ 62224-16-2 ]
[ 478374-81-1 ]

References: [1]Patent: EP1394147,2004,A1 .Location in patent: Page 73.

20
[ 62224-16-2 ]
[ 24067-17-2 ]
[ 666721-41-1 ]

Yield	Reaction Conditions	Operation in experiment
78%	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 80℃; for 3h;	(4-Nitrophenyl) boronic acid (1.2 equivalents), tetrakis (TRIPHENYLPHOSPHINE) palladium (0) (0.03 equivalent) and 2. 0M potassium phosphate solution (2.1 equivalents) are added to a solution under nitrogen of methyl 4-BROMOTHIOPHENE-2-CARBOXYLATE in 3.0 ml of degassed DME. The reaction medium is then stirred for 3 hours at 80oC, diluted with ethyl acetate (20 ml), washed with water (2X15 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. Chromatography of the residue on silica gel (98/2 dichloromethane/methanol) allows 1.94 g of the expected product to be isolated. Yield: 78% H NMR (CDC13) 5 (PPM) : 3.92 (s, 3H), 7.75 (d, 2H), 7.82 (s, 1H), 8.12 (s, 1H), 8.30 (d, 2H)
78%	With potassium phosphate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 80℃; for 3h;	To a solution of <strong>[62224-16-2]methyl 4-bromothiophen-2-carboxylate</strong> and 1.2 equivalents of (4-nitrophenyl) boronic acid in DME were added 2. [1] equivalents of a 2.0 M solution of potassium phosphate and 0.03 equivalent of tetrakis (triphenylphosphie) palladium (0). After stirring at [80XB0;C] for 3 hours the mixture was concentrated under reduced pressure. The residue was diluted with ethyl acetate, filtered over Celite, washed with water, dried over sodium sulfate, and then concentrated under vacuum. The residue was purified on a silica gel column using 9: [1] cyclohexane: ethyl acetate to yield 1.94 g (78%) of the desired compound.

References: [1]Patent: WO2005/3114,2005,A1 .Location in patent: Page 20.
[2]Patent: WO2004/14381,2004,A2 .Location in patent: Page/Page column 42-43.

21
[ 62224-16-2 ]
[ 87199-17-5 ]
[ 851340-17-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate;methyl (triphenylphosphoranylidene)acetate; In tetrahydrofuran; water; at 90 - 100℃;	Step 3 4-Bromo-thiophene-2-carboxylic acid methyl ester (8.67g), 4-Formylphenylboronic acid (13 g), Pd (PPh3) 4 (2.08g), THF (100mL), Na2CO3 aqueous solution (100 mL, 2M) were refluxed overnight (90~100C), then extracted the reaction mixture with EtOAc, and washed the organic layer by 5% NaOH solution, followed by water and brine, then dried over Na2SO4, After evaporation, the residue was washed with Et20 and afforded 4- (4- Formyl-phenyl)-thiophene-2-carboxylic acid methyl ester (7 g).

References: [1]Patent: WO2005/40161,2005,A1 .Location in patent: Page/Page column 77-78.

22
[ 62224-16-2 ]
[ 31862-80-3 ]

Yield	Reaction Conditions	Operation in experiment
	In sulfuric acid;	c 4-Bromo-5-nitrothiophene-2-carboxylic acid Methyl Ester The nitrating mixture (HNO3 d=1.42, 2 mL; concentrated H2SO4, 6 mL) was slowly added with stirring, at -5 to -10 C., to <strong>[62224-16-2]4-Bromothiophene-2-carboxylic acid methyl ester</strong> (3 g, 13.57 mmol) dissolved in concentrated H2SO4 (10 mL). After being kept at -5 to -10 C. for 30 min. the mixture was poured over crushed ice. The solid precipitate was separated by filtration and washed with water and dried over P2O5 to give 3.7 g of 4-bromo-5-nitrothiophene-2-carboxylic acid methyl ester as a tan solid, which was used in the next step without further purification.
	With sulfuric acid; nitric acid; at -10 - -5℃; for 0.5h;	The nitrating mixture (HNO3 d =1.42, 2 ML ; concentrated H2SO4, 6 mL) was slowly added with stirring, AT-5o TO-10oC, to 4-Bromothiophene-2- carboxylic acid methyl ester (3 g, 13.57 mmol) dissolved in concentrated H2S04 (10 mL). After being kept at-5 to-10oC for 30 min. the mixture was poured over crushed ice. The solid precipitate was separated by filtration and washed with water and dried over P205 to give 3.7 g of 4-bromo-5- nitrothiophene-2-carboxylic acid methyl ester as a tan solid, which was used in the next step without further purification.

References: [1]Patent: US2004/9995,2004,A1 .
[2]Patent: WO2003/99805,2003,A1 .Location in patent: Page 151.

23
[ 62224-16-2 ]
[ 1679-18-1 ]
[ 848483-63-6 ]

Yield	Reaction Conditions	Operation in experiment
47.3%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 20 - 60℃; for 66h;	2.72a. methyl 4-(4-chloro-phenyl)-thiophene-2-carboxylate 420 mg (1.25 mmol) of <strong>[62224-16-2]methyl 4-bromo-thiophene-2-carboxylate</strong> are dissolved in 10 mL dioxane and 5 mL 2M Na2CO3 solution. 196 mg (0.06 mmol) of 4-chloro-phenyl-boric acid and 72 mg (0.06 mmol) of tetrakis-(triphenylphosphine)-palladium are added successively, the reaction is refluxed for 6 h and stirred for a further 60 h at RT. After being heated again, the hot reaction solution is suction filtered through a glass fibre filter, washed with dioxane, combined with semisaturated NaHCO3 solution and extracted with EtOAc. The combined organic phases are dried over MgSO4. After elimination of the drying agent and solvent the residue is purified by column chromatography on silica gel (petroleum ether/ethyl acetate 9:1). Yield: 150 mg (47.3% of theory); C12H9ClO2S (M=252.72); calc.: molar peak (M+H)+: 253/255 fnd.: molar peak (M+H)+: 253/255; Retention time HPLC: 6.21 min (method B).

References: [1]Patent: US2004/242572,2004,A1 .Location in patent: Page/Page column 83-84.

24
[ 62224-16-2 ]
[ 128344-92-3 ]
methyl 4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-anthryl)-2-thiophenecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 3 Preparation of methyl 4-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-anthryl)-2-thiophene carboxylate Following the basic procedure of Example 1, beginning with 9.5 g (30 mmol) of 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-bromoanthracene and 4.6 g (21 mmol) of <strong>[62224-16-2]methyl 4-bromo-2-thiophenecarboxylate</strong>, 2.87 g (36%) of the expected methyl ester were obtained in the form of an amorphous solid.

References: [1]Patent: US5723499,1998,A .

25
[ 62224-16-2 ]
[ 73183-34-3 ]
[ 709648-80-6 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium acetate;1,1'-bis-(diphenylphosphino)ferrocene; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 85℃; for 40h;	Example 1 : Methyl 4-{6-[4-(2-piperidin-l-ylethoxy)phenyllpyrazolo[l,5-alpyrimdin-3-vUthiophene- 2-carboxylate; Step 1 : methyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)thiophene-2-carboxylate; 4-Bromothiophene-2-carboxylic acid (0.418 g, 2 mmol) was dissolved in methanol (1 mL), and concentrated sulfuric acid (0.039 g, 0.4 mmol) was added. The mixture was refluxed for 1O h, poured into water, and subjected to 3-fold extraction with ethyl acetate. The organic layer was washed with K2CO3- solution, concentrated, dried over MgSO4, filtered and evaporated to give methyl 4-bromothiophene-2- carboxylate, weight 0.4 g (90% yield).A flask containing PdCl2(dppf) (0.32 g, 0.43 mmol), dppf (0.24 g, 0.43 mmol), KOAc (4.23 g, 0.043 mol), and pinacolediborone (5.5 g, 0.021 mol) was flushed with argon, then a solution of the ester from the foregoing step (3.2 g, 0.014 mol) in dioxane (60 mL) was added. The mixture was stirred at 850C under argon atmosphere for 40 h. Water (5-fold excess) was added, and the mixture was subjected to 3-fold extraction with ethyl acetate. The organic layer was washed with brine, concentrated, dried over MgSO4, filtered, and evaporated to give the crude methyl 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)thiophene- 2-carboxylate (5.1 g, purity 85% according to 1H NMR data). This crude boronate was used without further purification.

References: [1]Patent: WO2007/85873,2007,A1 .Location in patent: Page/Page column 18.

26
[ 62224-16-2 ]
[ 1007110-53-3 ]
[ 1047645-53-3 ]

Yield	Reaction Conditions	Operation in experiment
66%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; water; at 70℃; for 2h;	To a solution of <strong>[62224-16-2]methyl 4-bromo-2-thiophenecarboxylate</strong> (1.0 g, 4.52 mmol) in dioxane/H2O (5:1 , 6 mL) was added K2CO3 (1.86 g, 13.5 mmol), tetrakistriphenylphosphine Pd(O) (260 mg, 0.23 mmol) and 1 -ethyl-5-(4, 4,5,5- tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 /-/-pyrazole(1.3 g, 5.85 mmol). The reaction mixture was heated to 70 C in a sealed tube. After 2h, the reaction mixture was concentrated under vacuum and purified on silica (hex/EtOAc, 20-40%) to afford methyl 4-(1 -ethyl-1 H-pyrazol-5-yl)-2-thiophenecarboxylate (0.7 g, 66%) as a light yellow solid: LC-MS (ES) m/z = 237 (M+H)+.To a solution of the above compound (0.5 g, 2.11 mmol) in THF (10 mL) was added NCS (0.364g, 2.74 mmol). The reaction mixture was heated to 70 C under nitrogen. After 2h, the reaction mixture was concentrated under vacuum and purified on silica (Hexanes/EtOAc, 10-20%) to afford the title compound (0.45 g, 78%) as a light yellow solid: LC-MS (ES) m/z 271 (M+H)+.

References: [1]Patent: WO2008/98104,2008,A1 .Location in patent: Page/Page column 162.

27
[ 62224-16-2 ]
[ 1044851-76-4 ]
[ 1047629-03-7 ]

Yield	Reaction Conditions	Operation in experiment
100%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 80℃; for 18h;Sealed tube;	To a solution of methyl 4-bromothiophene-2-car- boxylate (1.00 g, 4.52 mmol) in dioxane/H20 (30:3 mE) was added K2C03 (2.69 g, 19.45 mmol), tetrakistriphenylphosphine Pd(O) (0.78 g, 0.678 mmol), and 5-(5,5-dimethyl-1, 3,2-dioxaborinan-2-yl)-1 -methyl-i H-pyrazole (2.68 g,12.89 mmol). The reaction mixture was heated to 80 C. in a sealed tube for 18 h. The reaction solution was concentrated under vacuum and purified on silica gel (hexanes/ EtOAc, 4:1) to give the title compound methyl 4-(i-methyl- 1H-pyrazol-5-yl)thiophene-2-carboxylate (1.01 g, 100%) as yellow solid. ?H NMR (400 MHz, DMSO-d): oe 8.16 (d, 1H, J=i.6 Hz), 8.02 (d, 1H, J=i.6 Hz), 7.44 (d, 1H=2.0 Hz), 6.56 (d, 1H, J=2.0 Hz), 3.93 (s, 3H), 3.85 (s, 3H); MS (ESI):Calcd, for C1OH1ON2O2S: 222.1, found 223.1 (M+i).
	With potassium carbonate;bis(tri-t-butylphosphine)palladium(0); In 1,4-dioxane; water; at 80℃; for 1h;	To a solution of <strong>[62224-16-2]methyl 4-bromo-2-thiophenecarboxylate</strong> (1 g, 4.52 mmol) in dioxane/H2O (5:1 , 16 ml.) was added K2CO3 (2.7 g, 19 mmol), bis(tri-t- butylphosphine)palladium(O) (116 mg, 0.226 mmol) and 5-(5,5-dimethyl-1 ,3,2- dioxaborinan-2-yl)-1-methyl-1 H-pyrazole (1.2 g, 5.88 mmol). The reaction mixture was heated to 80 C in a sealed tube. After 1 h, the reaction was partitioned <n="136"/>between H2O-DCM and the aqueous phase was extracted several times with DCM. The combined organic fractions were dried over Na2SO4, concentrated and used directly: LCMS (ES) m/z 223 (M+H)+.

References: [1]Patent: US2018/201610,2018,A1 .Location in patent: Paragraph 0403; 0404.
[2]Patent: WO2008/98104,2008,A1 .Location in patent: Page/Page column 134-135.

28
[ 62224-16-2 ]
4-(2-methylimidazo[1,2-a]pyridin-3-yl)pyrimidin-2-amine [ No CAS ]
[ 1204527-64-9 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene;palladium diacetate; In 1,4-dioxane; at 130℃;Inert atmosphere;	To a stirred solution of Int-2 (0.5 g, 2.26 mmol) in THF (35 mL) was added Int-1 (0.51 g, 2.26 mmol) followed by Pd(OAc)2 (105 mg, 0.45 mmol), xanthpos (265 mg, 0.497 mmol) and CS2CO3 (1.35 g, 4.07 mmol). The reaction mixture was degassed under vacuum, bubbled with N2 for 10 minutes and stirred at 130 C. in a sealed tube for 20 hours. The reaction mixture was concentrated under reduced pressure and was purified by column chromatography to isolate product and a very close spot together. This mixture of two compounds (int-3+close impurity) was used directly in the next step. (Crude yield: 0.25 g). Mass (m/z): 366.0 [M++1]. 1H NMR (200 MHz, dmso-d6): delta 10.18 (s, 1H), 9.72 (brs, 1H), 8.59 (d, J=5.2 Hz, 1H), 7.98 (s, 1H), 7.62 (d, J=8 Hz, 1H), 7.42 (t, J=5.2 Hz, 1H), 7.18 (d, J=5.2 Hz, 1H), 7.02 (t, J=5.2 Hz, 1H), 7.11 (s, 1H), 3.82 (s, 3H), 2.62 (s, 3H). To a stirred solution of Int-3 (crude 0.25 g) in THF: MeOH: H2O (2:1:2) (25 ml) was added LiOH (0.25 g, wt/wt) at 0 C. and stirred while heating at 50 C. for 6 hours. Volatiles from the reaction mixture were distilled off under reduced pressure. Water (15 mL), DCM (50 ml) were added and stirred vigorously for 15 minutes, the aqueous layer was separated and treated again with DCM (35 ml). The aqueous layer was concentrated to half of its volume under reduced pressure and was acidified to about pH 5-6 with concentrated HCl. The precipitated solid was filtered and dried under vacuum to afford pure Int-4 (0.12 g). Mass (m/z): 352.0 [M++1]. 1H NMR (200 MHz, dmso-d6): delta 9.98 (s, 1H), 9.67 (brs, 1H), 8.60 (d, J=5.2 Hz, 1H), 7.65-7.59 (m, 3H) 7.42 (t, J=8.4 Hz, 2H), 7.15-6.98 (m, 2H), 2.67 (s, 3H). To a stirred solution of Int-4 (120 mg, 0.32 mmol) in DMF (10 mL) at 10 C. was added EDCI.HCl (136 mg, 0.71 mmol), HOBt (45 mg, 3.21 mmol), NH2OTHP (76 mg, 0.64 mmol) and finally DIPEA (0.143 mL, 0.80 mmol) was added and stirred at room temperature for 16 hours. The reaction was quenched with water (45 mL) and extracted with EtOAC (40 mL). The organic layer was washed with water (2×15 mL), brine (30 mL), dried over Na2SO4 and concentrated under vacuum to obtain crude compound which was purified by column chromatography eluting pure compound with 2% MeOH-DCM to afford pure Int-5 (50 mg, 33%). Mass (m/z): 451.2 [M++1]. 1H NMR (200 MHz, dmso-d6): delta 11.67 (brs, 1H), 10.06 (s, 1H), 9.74 (brs, 1H), 8.54 (d, J=5.2 Hz, 1H), 7.84 (s, 1H), 7.72 (s, 1H), 7.64 (d, J=9 Hz, 1H), 7.43 (t, J=7.8 Hz, 1H), 7.10 (d, J=5.6 Hz, 1H), 7.02 (t, J=5.8 Hz, 1H), 4.95 (s, 1H), 4.03 (s, 1H), 3.54 (s, 1H), 2.65 (s, 3H), 1.71 (s, 3H), 1.54 (s, 3H). To a stirred solution of Int-5 (50 mg, 0.105 mmol) in MeOH (4 mL) at 0-5 C. was added concentrated HCl (0.5 mL) dropwise and stirred at room temperature for 16 hours. The precipitated solid was filtered and dried under vacuum; this was then suspended in saturated aqueous HCO3 solution (5 mL) and stirred for 0.5 hours, this was filtered, washed with water (2 ml) and dried under vacuum to afford the title compound as a light brown solid (30 mg, 77%). Mass (m/z): 367.1[M++1]. 1H NMR (500 MHz, dmso-d6): delta 11.28 (brs, 1H), 10.00 (s, 1H), 9.78 (brs, 1H), 8.98 (brs, 1H), 8.54 (d, J=5.5 Hz, 1H), 7.64 (d, J=9 Hz, 1H), 7.59 (brs, 1H), 7.45-7.42 (m, 1H), 7.09 (d, J=5.5 Hz, 1H), 7.05-7.03 (m, 2H), 2.66 (s, 3H).

References: [1]Patent: US2010/29638,2010,A1 .Location in patent: Page/Page column 120.

29
[ 552846-17-0 ]
[ 62224-16-2 ]
[ 1239576-68-1 ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate;bis(tri-t-butylphosphine)palladium(0); In 1,4-dioxane; water; at 85℃; for 6h;Sealed flask;	Example 2; Preparation of Lambda/-{(1 S)-2-amino-1-[(3,4-difluorophenyl)methyl1ethyl}-5-chloro-4-(1 /-/- pyrazol-4-yl)-2-thiophenecarboxamide; a) 1 ,1-dimethylethyl 4-{5-[(methyloxy)carbonyl]-3-thienyl}-1 H-pyrazole-1-carboxylate; To a 75 ml. sealed flask was added <strong>[62224-16-2]methyl 4-bromo-2-thiophenecarboxylate</strong> (1.144 g, 5.17 mmol) [prepared according to the procedure of Example 1], potassium carbonate (2.31 g, 16.71 mmol), 1 ,1-dimethylethyl 4-(4,4, 5, 5-tetramethyl-1 , 3,2- dioxaborolan-2-yl)-1 H-pyrazole-1-carboxylate (1.656 g, 5.63 mmol) and bis(tri-t- butylphosphine)palladium(O) (35.1 mg, 0.069 mmol) in 1 ,4-dioxane (20 ml.) and H2O (4 ml_). After stirring for 6 hours at 85 0C, the reaction solution was diluted with CHCI3 (75 ml.) and washed with H2O. The organic layer was dried over Na2SO4, filtered and concentrated. The residue was adsorbed onto silica gel and eluted with [Hexanes/EtOAc, 2:1 ] to give the product [774 mg, quant.] as a yellow oil: LCMS (ES) m/z 309 (M+H)+.

References: [1]Patent: WO2010/93885,2010,A1 .Location in patent: Page/Page column 40-41.

30
[ 62224-16-2 ]
[ 761446-45-1 ]
[ 1239576-63-6 ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate;bis(tri-t-butylphosphine)palladium(0); In 1,4-dioxane; water; at 85℃; for 3h;Sealed flask;	b) methyl 4-[1-(phenylmethyl)-1 H-pyrazol-4-yl]-2-thiophenecarboxylate; To a 75 ml. sealed flask was added <strong>[62224-16-2]methyl 4-bromo-2-thiophenecarboxylate</strong> (1.6 g, 7.2 mmol), potassium carbonate (3.2 g, 23 mmol), 1-(phenylmethyl)-4-(4,4,5,5- tetramethyl-1 ,3,2-dioxaborolan-2-yl)-1 H-pyrazole (2.4 g, 8.1 mmol) and bis(tri-t- butylphosphine)palladium(O) (53 mg, 0.104 mmol) in 1 ,4-dioxane (20 ml.) and H2O (4 ml_). After stirring for 3 hours at 85 0C, the reaction solution was diluted with CHCI3 (75 ml.) and washed with H2O. The organic layer was dried over Na2SO4, filtered and concentrated. The reaction residue was purified on silica gel [Hexanes/EtOAc, 5:1 ] to give the product [2.4 g, quant.] as a yellow oil: LCMS (ES) m/z 258 (M+H)+.

References: [1]Patent: WO2010/93885,2010,A1 .Location in patent: Page/Page column 38.

31
[ 62224-16-2 ]
[ 1266112-22-4 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 528 - 530.

32
[ 62224-16-2 ]
[ 1448423-03-7 ]

References: [1]Synthetic Communications,2013,vol. 43,p. 2809 - 2816.

33
[ 62224-16-2 ]
[ 115-19-5 ]
[ 1448422-93-2 ]

References: [1]Synthetic Communications,2013,vol. 43,p. 2809 - 2816.

34
[ 62224-16-2 ]
(S)-2-({4-[3-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)propyl]thiophene-2-carbonyl}amino)pentanedioic acid [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 6938 - 6959.

35
[ 62224-16-2 ]
[ 130073-86-8 ]

References: [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 6938 - 6959.

Historical Records

Technical Information

• Acyl Group Substitution • Alkyl Halide Occurrence • Bouveault-Blanc Reduction • Catalytic Hydrogenation • Complex Metal Hydride Reductions • Ester Cleavage • General Reactivity • Grignard Reaction • Hiyama Cross-Coupling Reaction • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Dihalides • Reactions with Organometallic Reagents • Specialized Acylation Reagents-Carbodiimides and Related Reagents • Stille Coupling • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling

Related Functional Groups of
[ 62224-16-2 ]

Bromides

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4-Bromo-5-methylthiophene-2-carboxylic acid

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3-Bromothiophene-2-carboxylic acid

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Esters

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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

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CAS No.: 62224-16-2

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