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[ CAS No. 65130-46-3 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

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Chemical Structure| 65130-46-3

Chemical Structure| 65130-46-3

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Quality Control of [ 65130-46-3 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 65130-46-3 ]

Product Details of [ 65130-46-3 ]

CAS No. :	65130-46-3	MDL No. :	MFCD11180274
Formula :	C₈H₈BrF	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	PHGMUOJCQCLPBD-UHFFFAOYSA-N
M.W :	203.05	Pubchem ID :	13389030
Synonyms :

Calculated chemistry of [ 65130-46-3 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.25
Num. rotatable bonds :	1
Num. H-bond acceptors :	1.0
Num. H-bond donors :	0.0
Molar Refractivity :	44.04
TPSA :	0.0 Å²

Pharmacokinetics

GI absorption :	Low
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.42 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.37
Log Po/w (XLOGP3) :	2.98
Log Po/w (WLOGP) :	3.38
Log Po/w (MLOGP) :	3.83
Log Po/w (SILICOS-IT) :	3.41
Consensus Log Po/w :	3.19

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-3.35
Solubility :	0.0898 mg/ml ; 0.000442 mol/l
Class :	Soluble
Log S (Ali) :	-2.64
Solubility :	0.461 mg/ml ; 0.00227 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.97
Solubility :	0.0218 mg/ml ; 0.000107 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.97

Safety of [ 65130-46-3 ]

Signal Word:	Danger	Class:	8
Precautionary Statements:	P501-P260-P270-P271-P264-P280-P362+P364-P303+P361+P353-P301+P330+P331-P301+P312+P330-P304+P340+P310-P305+P351+P338+P310-P405	UN#:	3265
Hazard Statements:	H302+H312+H332-H314	Packing Group:	Ⅱ
GHS Pictogram:

Application In Synthesis of [ 65130-46-3 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 65130-46-3 ]
Downstream synthetic route of [ 65130-46-3 ]

[ 65130-46-3 ] Synthesis Path-Upstream 1~7

1
[ 52780-14-0 ]
[ 65130-46-3 ]

Yield	Reaction Conditions	Operation in experiment
80%	With phosphorus tribromide In dichloromethane at 20℃; for 16 h;	Example 168; 4-[4-[l-(3-Bromo-phenyl)-eihoxy]-2-(^yrido[23-d]pyrimidin-4-ylarnino)-phenylsulfanyl]-phenol; Example 168a; 1 -( 1 -Bromo-ethyl)-4-fluoro-benzene; [0612] To a solution of l-(3-Bromo-phenyl)-ethanol (7.0 g, 34.0 mmol) in dichloromethane (40 mL) was added drop wise phosphorus tribromide (77 g, 34.0 mmol) .The mixture was stirred at room temperature for 16 h. The reaction was poured onto ice/water. The aqueous phase was made basic with sodium bicarbonate. The aqueous phase was extracted with dichloromethane. The organic phase was washed with water, brine, and dried over sodium sulfate, filtered and concentrated under vacuum giving the title compound (7.8 g, 80 percent).

Reference： [1] Patent: WO2007/76034, 2007, A2, . Location in patent: Page/Page column 168

2
[ 459-47-2 ]
[ 65130-46-3 ]

Yield	Reaction Conditions	Operation in experiment
80%	With N-Bromosuccinimide; dibenzoyl peroxide In tetrachloromethane at 80℃; for 5 h;	(±)4(14romoethyI)41uorobenzene.A mixture of 1-ethyi-4-fluorohenzene (0248g, 2mmol), NBS (0.35g. 2mmol) and benzoyl peroxide (0. 14g, 0.6mmoi) were dissolved in 20 mL Cd4, The mixture was stirred at 0 °C for 5 hours and then the reaction was cone. in vacuo and resulting oil was purified via silica gel chromatography (PE-EtOAC 5: 1) to give the title compound (330 mg, 80percent) as a yellow oil. LCMS 202 (M ± Hj.

Reference： [1] Patent: WO2013/120104, 2013, A2, . Location in patent: Paragraph 00330

3
[ 403-41-8 ]
[ 65130-46-3 ]

Yield	Reaction Conditions	Operation in experiment
83%	With phosphorus tribromide In dichloromethane at 4 - 20℃; for 4 h;	1-(4-fluorophenyl)ethanol (1 equiv., 25 g) was taken up in dichloromethane (150 mL), and PBr3 (0.7 equiv., 12 mL) was added dropwise at 4° C. over a period of 20 min. The reaction mixture was stirred for 4 h at room temperature, then added to iced water (200 g) and extracted with dichloromethane (3*100 mL). The combined organic phases were dried over sodium sulphate, concentrated by evaporation in vacuo, and the liquid product (1-bromoethyl)-4-fluorobenzene was obtained (30 g, 83percent yield).
21.3%	With phosphorus tribromide In chloroform at 70℃; for 72 h;	A solution of 1-(4-fluorophenyl)ethanol (0.455 mL, 3.57 mmol) and phosphoms tribromide (0.673 mL, 7.13 mmol) in CHC13 (10 mL) was heated at 70 °C for 3 d. The reaction mixture was quenched in ice water and diluted in ethyl acetate. The organic layer was separated and washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated in vacuo to get the crudematerial. The cmde product was purified on a silica gel column with Hexanes/CH2C1(2/1) to afford 1-(1-bromoethyl)-4-fluorobenzene (154 mg, 0.758mo1, 21.3 percent) as acolourless oil. ‘H NMR (400 MHz, CHLOROFORM-d) ö 7.49 - 7.40 (m, 2H), 7.09 - 7.00(m, 2H), 5.23 (q, J=7.0 Hz, 1H), 2.06 (d, J=6.8 Hz, 3H).

Reference： [1] Journal of the American Chemical Society, 2016, vol. 138, # 34, p. 10774 - 10777
[2] Patent: US2012/46301, 2012, A1, . Location in patent: Page/Page column 30; 31
[3] Patent: WO2018/148626, 2018, A1, . Location in patent: Page/Page column 152
[4] Tetrahedron, 1977, vol. 33, p. 1581 - 1585
[5] Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical & Analytical, 1984, vol. 23, # 1, p. 60 - 62
[6] Patent: US2004/142940, 2004, A1, . Location in patent: Page/Page column 48
[7] Angewandte Chemie - International Edition, 2016, vol. 55, # 34, p. 9969 - 9973[8] Angew. Chem., 2016, vol. 128, # 34, p. 10123 - 10127,5
[9] Patent: US2010/197725, 2010, A1, . Location in patent: Page/Page column 20
[10] Patent: WO2006/112828, 2006, A1, . Location in patent: Page/Page column 57

4
[ 405-99-2 ]
[ 332-42-3 ]
[ 65130-46-3 ]

Reference： [1] Organic and Biomolecular Chemistry, 2016, vol. 14, # 24, p. 5622 - 5626

5
[ 403-42-9 ]
[ 65130-46-3 ]

Reference： [1] Patent: US2012/46301, 2012, A1,
[2] Angewandte Chemie - International Edition, 2016, vol. 55, # 34, p. 9969 - 9973[3] Angew. Chem., 2016, vol. 128, # 34, p. 10123 - 10127,5

6
[ 462-06-6 ]
[ 65130-46-3 ]

Reference： [1] Patent: US2012/46301, 2012, A1,

7
[ 405-99-2 ]
[ 332-42-3 ]
[ 65130-46-3 ]

Reference： [1] Organic and Biomolecular Chemistry, 2016, vol. 14, # 24, p. 5622 - 5626

[ 65130-46-3 ] Synthesis Path-Downstream 1~80

1
[ 403-41-8 ]
[ 65130-46-3 ]

Yield	Reaction Conditions	Operation in experiment
83%	With phosphorus tribromide; In dichloromethane; at 4 - 20℃; for 4h;	1-(4-fluorophenyl)ethanol (1 equiv., 25 g) was taken up in dichloromethane (150 mL), and PBr3 (0.7 equiv., 12 mL) was added dropwise at 4 C. over a period of 20 min. The reaction mixture was stirred for 4 h at room temperature, then added to iced water (200 g) and extracted with dichloromethane (3*100 mL). The combined organic phases were dried over sodium sulphate, concentrated by evaporation in vacuo, and the liquid product (1-bromoethyl)-4-fluorobenzene was obtained (30 g, 83% yield).
21.3%	With phosphorus tribromide; In chloroform; at 70℃; for 72h;	A solution of 1-(4-fluorophenyl)ethanol (0.455 mL, 3.57 mmol) and phosphoms tribromide (0.673 mL, 7.13 mmol) in CHC13 (10 mL) was heated at 70 C for 3 d. The reaction mixture was quenched in ice water and diluted in ethyl acetate. The organic layer was separated and washed with water followed by brine, dried over anhydrous sodium sulfate and concentrated in vacuo to get the crudematerial. The cmde product was purified on a silica gel column with Hexanes/CH2C1(2/1) to afford 1-(1-bromoethyl)-4-fluorobenzene (154 mg, 0.758mo1, 21.3 %) as acolourless oil. ?H NMR (400 MHz, CHLOROFORM-d) oe 7.49 - 7.40 (m, 2H), 7.09 - 7.00(m, 2H), 5.23 (q, J=7.0 Hz, 1H), 2.06 (d, J=6.8 Hz, 3H).
	With hydrogen bromide; In water; at 0 - 20℃; for 3h;	4-Fluoro-alpha-methylbenzyl alcohol (7 g, 6.3 ml, 50 mmol) was added to 50 mL 48% aqueous solution of HBr at 0 C. The solution was allowed to stir at room temperature three hoursat which time it was extracted with hexane. After drying and concentrated, 10 g of a colorless oil was obtained. M+H+(203).

	With trimethylsilyl bromide; In dichloromethane; at 20℃; for 48h;Inert atmosphere;	10.1.1: 1-(1-Bromoethyl)-4-fluorobenzene 0.5 g of 1-(4-fluorophenyl)ethanol is dissolved in 20 cm3 of dichloromethane, under an inert atmosphere, at a temperature close to 20 C. 1.24 cm3 of pure bromo(trimethyl)silane are introduced in two lots to the reaction mixture. The latter is stirred at a temperature close to 20 C. for 48 h, then it is washed with a saturated aqueous solution of sodium chloride, dried over a phase separation cartridge and concentrated using a rotary evaporator under reduced pressure (5 kPa). The 700 mg of crude product obtained are purified by filtration through a silica pellet (eluent: 10% ethyl acetate/90% cyclohexane). After concentrating the fractions under reduced pressure, 439 mg of 1-(1-bromoethyl)-4-fluorobenzene are obtained in the form of a colorless thick oil. NMR: ppm: 1.98 (d, J=6.8 Hz, 3H) 5.53 (q, J=6.8 Hz, 1H) 7.19 (t, J=8.8 Hz, 2H) 7.56 (dd, J=8.8, 5.4 Hz, 2H) EI: [M]+ m/z=202; [M-Br]+ m/z=123
	With hydrogen bromide; In water; at 0 - 20℃; for 3h;	4-Fluoro-alpha-methylbenzyl alcohol (7g, 6.3ml, 50mmol) was added to 50 mL 48 % aqueous solution of HBr at 0 0C. The solution was allowed to stir 3 h at RT, at which time it was extracted with hexane. After drying and concentration, 10 g of a colorless oil was obtained. M+H+(203).
	With phosphorus tribromide; In dichloromethane; at 0 - 26℃; for 16h;	To a solution of 1 -(4-fluorophenyl)ethanol (500 mg, 0.0036 mol, commercial source: Apollo) in dichloromethane (5 mL) at 0 °C, PBr3 (0.5 mL, commercial source: TCI) was slowly added and the mixture stirred at 26 °C for 16 h. Upon completion, the reaction mixture was concentrated under reduced pressure. NaHCC>3 solution (70 mL) was added and extracted with ethyl acetate (3x30 mL). The organic layers were combined and washed with brine (50 mL), dried over Na2S04, filtered and concentrated to afford crude 1-(1-bromoethyl)-4-fluorobenzene (310 mg) as a brown liquid. It was used in the next step without further purification.

Reference： [1]Journal of the American Chemical Society,2016,vol. 138,p. 10774 - 10777
[2]Patent: US2012/46301,2012,A1 .Location in patent: Page/Page column 30; 31
[3]Patent: WO2018/148626,2018,A1 .Location in patent: Page/Page column 152
[4]Tetrahedron,1977,vol. 33,p. 1581 - 1585
[5]Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical and Analytical,1984,vol. 23,p. 60 - 62
[6]Patent: US2004/142940,2004,A1 .Location in patent: Page/Page column 48
[7]Angewandte Chemie - International Edition,2016,vol. 55,p. 9969 - 9973
Angew. Chem.,2016,vol. 128,p. 10123 - 10127,5
[8]Patent: US2010/197725,2010,A1 .Location in patent: Page/Page column 20
[9]Patent: WO2006/112828,2006,A1 .Location in patent: Page/Page column 57
[10]Patent: WO2019/34729,2019,A1 .Location in patent: Page/Page column 104

2
[ 75-18-3 ]
[ 65130-46-3 ]
1-(p-Fluorphenyl)aethyldimethylsulfoniumbromid [ No CAS ]

Reference： [1]Tetrahedron,1977,vol. 33,p. 1581 - 1585

3
[ 75-89-8 ]
[ 64-19-7 ]
[ 65130-46-3 ]
[ 403-41-8 ]
[ 2928-12-3 ]
1-(4-fluorophenyl)ethyl trifluoroethyl ether [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1984,vol. 106,p. 1383 - 1396

4
[ 67-56-1 ]
[ 75-89-8 ]
[ 65130-46-3 ]
[ 403-41-8 ]
1-(4-fluorophenyl)ethyl trifluoroethyl ether [ No CAS ]
[ 111662-72-7 ]

Reference： [1]Journal of the American Chemical Society,1984,vol. 106,p. 1383 - 1396

5
[ 75-89-8 ]
[ 65130-46-3 ]
[ 403-41-8 ]
[ 823189-13-5 ]
1-(4-fluorophenyl)ethyl trifluoroethyl ether [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1984,vol. 106,p. 1383 - 1396

6
[ 65130-46-3 ]
[ 105-53-3 ]
[ 155943-44-5 ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 1070 - 1083

8
[ 65130-46-3 ]
[ 141056-88-4 ]
(+/-)9-(4-Fluoro-α-methylbenzyl)-2-(2-fluorophenyl)-7,8,9,10-tetrahydro-imidazo[1,2-c]pyrido[3,4-e]pyrimidin-5(6H)-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 5043 - 5051

9
[ 65130-46-3 ]
[ 403-42-9 ]

Reference： [1]Catalysis Communications,2010,vol. 11,p. 923 - 927
[2]Tetrahedron Letters,2007,vol. 48,p. 1919 - 1921
[3]Synthetic Communications,2008,vol. 38,p. 4188 - 4197
[4]Bulletin of the Chemical Society of Ethiopia,2010,vol. 24,p. 277 - 282

10
[ 65130-46-3 ]
[ 1000887-16-0 ]
[ 1000887-17-1 ]

Yield	Reaction Conditions	Operation in experiment
		Example 18, 19 To lactam 115 (50 mg, 0.12 mmol, 1 equiv.) was added DMF (1.2 mL, 0.1 M) and cooled in an ice bath to 0° C. before added sodium hydride (5.5 mg, 0.14 mmol, 60percent mineral oil, 1.2 equiv.) and stirred for 5 minutes under nitrogen atmosphere. Bromide 121 (50 mg, 0.17 mmol, 1.5 equiv) was added and the reaction was allowed to stir for 30 minutes at 0° C. The reaction was quenched with water and diluted with Ethyl Acetate. The organic layer was washed with water and brine before being dried over sodium sulfate, filtered and concentrated in vacuo. The crude residue was purified by silica gel chromatography eluting with 4/1 EtOAc/Hexanes to afford the desired products 122 diastereomer A (first to elute off column) and 123 diastereomer B (second to elute of column) 121.

Reference： [1]Patent: US2008/58315,2008,A1 .Location in patent: Page/Page column 28

11
[ 81477-94-3 ]
[ 65130-46-3 ]
C₂₇H₂₈NO₂F [ No CAS ]
C₂₇H₂₈NO₂F [ No CAS ]

Reference： [1]Organic Letters,2007,vol. 9,p. 3945 - 3948

12
[ 81477-94-3 ]
[ 98-88-4 ]
[ 65130-46-3 ]
C₂₁H₂₄NO₃F [ No CAS ]
C₂₁H₂₄NO₃F [ No CAS ]

Reference： [1]Organic Letters,2007,vol. 9,p. 3945 - 3948

13
[ 81477-94-3 ]
[ 98-88-4 ]
[ 65130-46-3 ]
C₂₁H₂₄NO₃F [ No CAS ]
C₂₁H₂₄NO₃F [ No CAS ]
C₂₁H₂₄NO₃F [ No CAS ]

Reference： [1]Organic Letters,2007,vol. 9,p. 3945 - 3948

14
[ 65130-46-3 ]
[ 155943-75-2 ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 1070 - 1083

15
[ 65130-46-3 ]
[ 1026290-72-1 ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 1070 - 1083

16
[ 65130-46-3 ]
2-[1-(4-Fluoro-phenyl)-ethyl]-malonic acid monoethyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 1070 - 1083

17
[ 65130-46-3 ]
[ 150881-66-6 ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 1070 - 1083

18
[ 65130-46-3 ]
(S)-2-[3-(4-Fluoro-phenyl)-2-mercaptomethyl-butyrylamino]-propionic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 1070 - 1083

19
[ 65130-46-3 ]
(S)-2-[3-(4-Fluoro-phenyl)-2-mercaptomethyl-butyrylamino]-3-(4-hydroxy-phenyl)-propionic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 1070 - 1083

20
[ 65130-46-3 ]
[ 150881-46-2 ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 1070 - 1083

21
[ 65130-46-3 ]
(S)-2-[2-Acetylsulfanylmethyl-3-(4-fluoro-phenyl)-butyrylamino]-3-(4-hydroxy-phenyl)-propionic acid benzyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 1070 - 1083

22
[ 65130-46-3 ]
(S)-3-(4-Acetoxy-phenyl)-2-[2-acetylsulfanylmethyl-3-(4-fluoro-phenyl)-butyrylamino]-propionic acid benzyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 1070 - 1083

23
[ 75336-86-6 ]
[ 65130-46-3 ]
[ 672293-44-6 ]

Yield	Reaction Conditions	Operation in experiment
90%	In DMF (N,N-dimethyl-formamide); at 20℃;	To 6.4 g 1-(4-fluorophenyl)-ethyl bromine in 100 mL DMF was added the piperazine. The mixture was then stirred overnight at room temperature. The solution was evaporated and the residue was then filtrated on a small quantity of silica gel, washing with ethyl acetate and methanol. Purification was carried out using flash chromatography, CHCl3/MeOH/Et3N=90/8/2 (or AcOEt/MeOH=90/10). 6.2 g (90percent) of pure compound (mixture inseparable of two diasteromers) was obtained. M+H+(223).

Reference： [1]Patent: US2004/142940,2004,A1 .Location in patent: Page/Page column 48

24
[ 65130-46-3 ]
2-(4-Fluoro-α-methylbenzyl)-5-(4-methylsulfonylphenyl)-6-(4-fluorophenyl)-3(2H)-pyridazinone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 12 2-(4-Fluoro-alpha-methylbenzyl)-5-(4-methylsulfonylphenyl)-6-(4-fluorophenyl)-3(2H)-pyridazinone The title compound was prepared according to the method of Example 7, substituting 4-fluoro-alpha-methyl benzyl bromide (synthesised from 4-fluoro-alpha-methyl benzyl alcohol) for benzyl bromide. M.p. = 185-186°C. 1H NMR (300 MHz, CDCl3) 81.84 (d, J = 7 Hz, 3 H), 3.07 (s, 3 H), 6.43 (q, J = 7 Hz, 1 H), 6.91-7.11 (m, 7 H), 7.31 (d, J = 9 Hz, 2 H), 7.52 (m, 2 H), 7.9 (d, J = 9 Hz, 2 H). MS (DCI/NH3) m/e 467 (M + H)+, 484 (M + NH4)+.

Reference： [1]Patent: EP1005460,2006,B1 .Location in patent: Page/Page column 20

25
[ 403-41-8 ]
[ 65130-46-3 ]
2-(4-Fluoro-α-methylbenzyl)-5-(4-methylsulfonylphenyl)-6-(4-fluorophenyl)-3(2H)-pyridazinone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 12 2-(4-Fluoro-alpha-methylbenzyl)-5-(4-methylsulfonylphenyl)-6-(4-fluorophenyl)-3(2H)-pyridazinone The title compound was prepared according to the method of Example 7, substituting 4-fluoro-alpha-methyl benzyl bromide (synthesised from 4-fluoro-alpha-methyl benzyl alcohol) for benzyl bromide. M.p.=185-186° C. 1H NMR (300 MHz, CDCl3) 67 1.84 (d, J=7 Hz, 3H), 3.07 (s, 3H), 6.43 (q, J=7 Hz, 1H), 6.91-7.11 (m, 7H), 7.31 (d, J=9 Hz, 2H), 7.52 (m, 2H), 7.9 (d, J=9 Hz, 2H). MS (DCl/NH3) m/e 467 (M+H)+, 484 (M+NH4)+. Elemental Analysis: calculated for C25H20F2N2O3S: C, 64.36; H, 4.32; N, 6.00. Found: C, 64.38; H, 4.07; N, 5.93.

Reference： [1]Patent: US6525053,2003,B1

26
[ 75336-86-6 ]
[ 65130-46-3 ]
[ 672293-44-6 ]
[ 1076195-30-6 ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide; at 20℃;	To 6.4 g l-(4-fluororhohenyl)-ethyl bromine in 100 mL DMF was added the 2R- methylpiperazine. The mixture was then stirred overnight at room temperature. The solution was evaporated and the residue was then filtrated on a small quantity of silica gel, washing with ethyl acetate and methanol. Purification was carried out using flash chromatography, CHCl3/MeOH/Et3N=90/8/2 (or AcOEt/MeOH=90/10). 6.2 g (90 percent) of pure compound (mixture inseparable of two diasteromers) was obtained. M+H+(223).

Reference： [1]Patent: WO2006/112828,2006,A1 .Location in patent: Page/Page column 57

Yield	Reaction Conditions	Operation in experiment
		b) 1-(4-Fluorophenyl)-1-bromoethane was prepared by dissolving 20.75 g (79 mmol) of triphenyl phosphine in 100 mL of dichloromethane and adding 12.68 g (79 mmol) of bromine. To this mixture was added 10.1 g of the crude product prepared in Example 31(a) above. The triphenylphosphine oxide which formed was removed by filtration and the solvent was evaporated under vacuum to yield crude 1-(4-fluorophenyl)-1-bromoethane which was used without further purification.
	With phosphorus tribromide; In diethyl ether; at 0 - 20℃;	General procedure: Example 44A 1-(1-bromoethyl)-3-chlorobenzene To a solution of 1-(3-chlorophenyl)ethanol (0.2 g, 1.28 mmol) in diethyl ether (10 mL) at 0° C. was added tribromophosphine (0.38 g, 1.41 mmol). The mixture was warmed to room temperature and stirred overnight, then diluted with ether (10 mL). After quenching with water (10 mL), the organic phase was separated, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel and eluted with petroleum ether to give the title compound as an oil (0.16 g, yield 57.1percent).

28
[ 610-78-6 ]
[ 65130-46-3 ]
[ 943774-64-9 ]

Yield	Reaction Conditions	Operation in experiment
66%	With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 16h;	Example 168b; 4-[l -(3-Bromo-phenyl)-ethoxy]-l -chloro-2-nitro-benzene; [0613] To Example 168a (7.8 g, 30 mmol) in DMF (50 mL) was added 4-chloro-3-nitro-phenol (5.14 g, 30.0 mmol), and K2CO3 (8.18 g, 60 mmol). The mixture was heated at 80 0C for 16 hr. The reaction was cooled and poured into water. The aqueous phase was extracted with ethyl acetate (2x) and the combined phases were washed with water, brine, and dried over sodium sulfate. The organic phase was concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with (hexanes/ethyl acetate 90:10) to give the title compound (7.0 g, 66 percent).

Reference： [1]Patent: WO2007/76034,2007,A2 .Location in patent: Page/Page column 168

29
[ 52780-14-0 ]
[ 65130-46-3 ]

Yield	Reaction Conditions	Operation in experiment
80%	With phosphorus tribromide; In dichloromethane; at 20℃; for 16h;	Example 168; 4-[4-[l-(3-Bromo-phenyl)-eihoxy]-2-(^yrido[23-d]pyrimidin-4-ylarnino)-phenylsulfanyl]-phenol; Example 168a; 1 -( 1 -Bromo-ethyl)-4-fluoro-benzene; [0612] To a solution of l-(3-Bromo-phenyl)-ethanol (7.0 g, 34.0 mmol) in dichloromethane (40 mL) was added drop wise phosphorus tribromide (77 g, 34.0 mmol) .The mixture was stirred at room temperature for 16 h. The reaction was poured onto ice/water. The aqueous phase was made basic with sodium bicarbonate. The aqueous phase was extracted with dichloromethane. The organic phase was washed with water, brine, and dried over sodium sulfate, filtered and concentrated under vacuum giving the title compound (7.8 g, 80 percent).

Reference： [1]Patent: WO2007/76034,2007,A2 .Location in patent: Page/Page column 168

30
[ 5654-95-5 ]
[ 65130-46-3 ]
[ 1115389-44-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In tetrahydrofuran;Heating;	To a THF solution of E1 and RI-Br (R1 = alpha-methyl-p-fluorobenzyl) will be added NaH (1.1 eq) and the solution will be heated until the starting material disappears. After removal of volatiles, the residue will be chromatographed to give compound E2.

Reference： [1]Patent: WO2009/20580,2009,A1 .Location in patent: Page/Page column 238

31
[ 13466-43-8 ]
[ 65130-46-3 ]
[ 1128105-63-4 ]

Yield	Reaction Conditions	Operation in experiment
59%		EXAMPLE 9; Step A:; To a solution of 77.1a (4.0 g, 22.98 mmol) in THF/DMF (20/20 ml) was added NaH (60percent, 1.1 O g, 27.6 mmol) at 0 0C and stirred for 10 min, followed with addition of 4-fluoro alpha-methyl benzyl bromide (5.57 g, 27.6 mmol). The resulting mixture was stirred overnight, then quenched with saturated aqueous NH4CI, extracted with EtOAc (3 X). The combination of organic layers was washed with brine, dried (Na2SO4), concentrated and purified by flash chromatography to afford product 77.1b as colorless oil (4.0 g, 59percent).
59%		To a solution of 1a (4.0 g, 22.98 mmol) in THF/DMF (20/20 ml) was added NaH (60percent, 1.10 g, 27.6 mmol) at 00C and stirred for 10 min, followed with addition of 1b (5.57 g, 27.6 mmol). The resulting mixture was stirred overnight, then quenched with saturated aqueous NH4CI, extracted with EtOAc (3 X). The combination of organic layers was washed with brine, dried (Na2SO4), concentrated and purified by flash chromatography to afford product 1c as colorless oil (4.0 g, 59percent).

Reference： [1]Patent: WO2009/32277,2009,A1 .Location in patent: Page/Page column 420
[2]Patent: WO2009/73777,2009,A1 .Location in patent: Page/Page column 166
[3]ACS Medicinal Chemistry Letters,2011,vol. 2,p. 471 - 476

32
[ 13466-38-1 ]
[ 65130-46-3 ]
[ 1128105-91-8 ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 25; Step A:; To the 0.9M solution 117.1a in THF/DMF (1 :1 ) was added 1.5 eq. of NaH was added at 0°C. After 10 minutes 1.5 eq. of 4-fluoro alpha-methyl benzyl bromide was added. The reaction was then allowed to stir overnight at room temperature. The reaction mixture was quenched with NH4CI solution and extracted with ethyl acetate. The combined organic layer was dried with Na2SO4 and then filtered. The filtrate was concentrated and the residue was purified by silica gel chromatography using ethyl acetate/hexanes to obtain 114.1a.

Reference： [1]Patent: WO2009/32277,2009,A1 .Location in patent: Page/Page column 439-440

33
[ 675-20-7 ]
[ 65130-46-3 ]
[ 1160359-87-4 ]

Yield	Reaction Conditions	Operation in experiment
56.6%		To a solution of 133a (3.25 g, 32.80 mmol) in THF/DMF (25/25 ml) was added NaH (60percent, 1.95 g, 49.25 mmol) at 0 °C and stirred for 10 min, followed with addition of 4-fluoro alpha-methyl benzyl bromide (10.00 g, 49.25 mmol). The resulting mixture was stirred overnight, then quenched with saturated aqueous NH4CI, extracted with EtOAc (3 X). The combination of organic layers was washed with brine, dried (Na2SO4), concentrated and purified by flash chromatography to afford product 133b as colorless oil (4.1 g, 56.6percent).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 664 - 669
[2]Patent: WO2009/73777,2009,A1 .Location in patent: Page/Page column 218

34
[ 1218940-99-8 ]
[ 65130-46-3 ]
[ 1218941-16-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 828 - 831

35
[ 1109230-25-2 ]
[ 65130-46-3 ]
[ 1109230-26-3 ]

Yield	Reaction Conditions	Operation in experiment
		A solution of 0.15 g of <strong>[1109230-25-2]5-bromo-3,4-dihydroisoquinolin-1(2H)-one</strong> in 5 cm3 of dimethylformamide is poured into a mixture containing 31 mg of sodium hydride (60percent in oil) and 10 cm3 of dimethylformamide at a temperature close to 20° C. under an inert atmosphere. Then a solution of 0.2 g of 1-(1-bromoethyl)-4-fluorobenzene in 5 cm3 of dimethylformamide is poured into the reaction mixture. The latter is stirred for 20 h at a temperature close to 20° C. Water and ethyl acetate are added to the reaction mixture. After decanting, the organic phase is washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate, filtered then concentrated using a rotary evaporator under reduced pressure (5 kPa). The 325 mg of crude product obtained are purified by filtration through a silica pellet (eluent: 20percent ethyl acetate/80percent cyclohexane). After concentrating the fractions under reduced pressure, 146 mg of 5-bromo-2-[1-(4-fluorophenyl)ethyl]-3,4-dihydroisoquinolin-1(2H)-one are obtained in the form of a thick pale yellow oil.NMR: ppm: 1.54 (d, J=7.3 Hz, 3H) 2.85 (m, 1H) 2.97 (m, 1H) 3.10 (m, 1H) 3.47 (m, 1H) 5.92 (q, J=7.3 Hz, 1H) 7.18 (t, J=8.8 Hz, 2H) 7.33 (t, J=8.1 Hz, 1H) 7.41 (dd, J=8.8, 5.9 Hz, 2H) 7.78 (dd, J=8.1, 1.4 Hz, 1H) 7.98 (dd, J=8.1, 1.4 Hz, 1H)LC-MS-DAD-ELSD: [M+H]+ m/z=348

Reference： [1]Patent: US2010/197725,2010,A1 .Location in patent: Page/Page column 21

36
[ 1160359-98-7 ]
[ 65130-46-3 ]
[ 1160358-81-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 664 - 669

37
[ 1064708-73-1 ]
[ 65130-46-3 ]
[ 1064708-35-5 ]

Yield	Reaction Conditions	Operation in experiment
75.5%		4-benzoylmethyl-4-piperidinol (II) is firstly prepared according to the method of synthesis and post-treatment in General Method one. Thereafter, 1.79g (8.8mmol) of <strong>[65130-46-3]1-(1-bromoethyl)-4-fluorobenzene</strong>, 1.75g (8.0mmol) of 4-benzoylmethyl-4-piperidinol (II), 0.03g (0.2mmol) of potassium iodide and 3.53g (25.6mmol) of anhydrous K2CO3 is placed in anhydrous acetone (60ml), and reacting at reflux for 12 hours. Operating according to the post-treatment procedure in General Method two obtains 2.39g of a white crystal, with yield of 75.5 percent. Element analysis: C21H24FNO2HClH2O (calculated valuepercent: C 63.71, H 6.87, N 3.54, Cl 8.96; found valuepercent: C 63.96, H 6.65, N 3.32, Cl 9.12) 1HNMR (DMSO-d6): delta 1.35(d, 3H, CH3), 1.80-2.10 (m, 4H, piperidine-H), 3.00-3.20 (m, 4H, piperidine-H), 3.16 (s, 2H, CH2CO), 4.03-4.10 (m, 1H, PhCH), 5.01(s, 1H, piperidine-N-HCl), 7.20-8.10 (m, 9H, ArH), 9.6-10.2(2B, 1H, piperidine-OH). MS : m/z 342(M+1)

Reference： [1]Patent: EP2305645,2011,A1 .Location in patent: Page/Page column 18

38
[ 1064708-73-1 ]
[ 65130-46-3 ]
[ 1064709-08-5 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; potassium iodide; In acetone; for 12h;Reflux;	III-20N-(1-(4-fluorophenyl)ethyl)-4-benzoylmethyl-4-piperidinol hydrochloride4-benzoylmethyl-4-piperidinol (II) is firstly prepared according to the method of synthesis and post-treatment in General Method one.Thereafter, 1.79 g (8.8 mmol) of <strong>[65130-46-3]1-(1-bromoethyl)-4-fluorobenzene</strong>, 1.75 g (8.0 mmol) of 4-benzoylmethyl-4-piperidinol (II), 0.03 g (0.2 mmol) of potassium iodide and 3.53 g (25.6 mmol) of anhydrous K2CO3 is placed in anhydrous acetone (60 ml), and reacting at reflux for 12 hours.Operating according to the post-treatment procedure in General Method two obtains 2.39 g of a white crystal, with yield of 75.5percent.Element analysis: C21H24FNO2.HCl.H2O (calculated value percent: C 63.71, H 6.87, N 3.54, Cl 8.96; found value percent: C 63.96, H 6.65, N 3.32, Cl 9.12)1HNMR (DMSO-d6): delta 1.35(d, 3H, CH3), 1.80-2.10 (m, 4H, piperidine-H), 3.00-3.20 (m, 4H, piperidine-H), 3.16 (s, 2H, CH2CO), 4.03-4.10 (m, 1H, PhCH), 5.01(s, 1H, piperidine-N.HCl), 7.20-8.10 (m, 9H, ArH), 9.6-10.2(2B, 1H, piperidine-OH).MS: m/z 342(M+1)

Reference： [1]Patent: US2011/105503,2011,A1 .Location in patent: Page/Page column 14

39
[ 65130-46-3 ]
[ 1160358-00-8 ]
[ 1160357-99-2 ]

Reference： [1]ACS Medicinal Chemistry Letters,2011,vol. 2,p. 471 - 476

40
[ 65130-46-3 ]
[ 1128103-39-8 ]

Reference： [1]ACS Medicinal Chemistry Letters,2011,vol. 2,p. 471 - 476

41
[ 65130-46-3 ]
[ 1128103-40-1 ]

Reference： [1]ACS Medicinal Chemistry Letters,2011,vol. 2,p. 471 - 476

42
[ 65130-46-3 ]
[ 1128103-43-4 ]

Reference： [1]ACS Medicinal Chemistry Letters,2011,vol. 2,p. 471 - 476

43
[ 462-06-6 ]
[ 65130-46-3 ]

Reference： [1]Patent: US2012/46301,2012,A1

44
[ 403-42-9 ]
[ 65130-46-3 ]

Reference： [1]Patent: US2012/46301,2012,A1
[2]Angewandte Chemie - International Edition,2016,vol. 55,p. 9969 - 9973
Angew. Chem.,2016,vol. 128,p. 10123 - 10127,5

45
[ 65130-46-3 ]
[ 516447-52-2 ]

Reference： [1]Patent: US2012/46301,2012,A1

46
[ 65130-46-3 ]
[ 57260-71-6 ]
[ 862270-46-0 ]

Yield	Reaction Conditions	Operation in experiment
50%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 2h;	<strong>[65130-46-3]1-(1-bromoethyl)-4-fluorobenzene</strong> (1.2 equiv., 18 g) and K2CO3 (2 equiv., 22 g) were added at room temperature to a solution of tert.-butyl-piperazine-1-carboxylate (1 equiv., 15 g) in DMF (15 mL) and stirred for 2 h. After adding cold water (20 mL) the mixture was extracted with hexane (10.x.60 mL). The combined organic phases were dried over sodium sulphate and acidified with 10percent HCl. The precipitate was suction filtered, washed with hexane (3.x.100 mL), adjusted to pH9 with K2CO3 and re-extracted with hexane (5.x.100 mL). The combined organic phases were dried over sodium sulphate. The removal of the solvent in vacuo yielded a viscous product (tert-butyl 4-(1-(4-fluorophenyl)ethyl)piperazine-1-carboxylate) (12.5 g, 50percent yield).

Reference： [1]Patent: US2012/46301,2012,A1 .Location in patent: Page/Page column 31

47
[ 1375202-52-0 ]
[ 65130-46-3 ]
[ 1450652-63-7 ]

Yield	Reaction Conditions	Operation in experiment
3%		Example 35. Synthesis of (±)-N-((4,6-dimethyI-2-oxo-42-dihydropyridin3-yI)methy1)-1-(1-(4fluorophenyI)ethv[)-2-methvl-1H4ndole-3carhoxamide (Compound166).N-((4,6-dimethyl-2-oxo- I ,2-dihydropvridin-3-yl )methyfl-2-methyl- I H-indole-3-carhoxamide (309 ing, 1 .Onimol) was dissolved in 4 mL DMF. NaK (80mg, 2.Onimol) was added, the mixture was stirred at room temperature for 30 mm, and then i?(1?bromnoetlwl,1?4?fluorobenzene (0,404mg, 2.Ommnol) was added. The mixture was stirred at room temperature overnight and was directly purified by reverse phase FIPLC (A:CH3CN,B:water-fO.1 percent HO. A:B=35:65 ASB C18 150*25mm) to afford the title compound as a white solidU I mg, yield 3percent). LCMS 432 (M H) 1F1 NMR (400 MHz, CDCI3) 6 7.78 (d,J8FIz, 1Ff), 7.33 (m, 11:1), 7.14 (s, 11:1), 6.96 (in, 2H), 6.92 (in, 1H), 6.85-6.92 (rn, 4H), 5.85 (s, 1H), 5.72 (rn, 1H), 4.56 (s, 2H), 2.64 (s, 3H), 2.37 (s, 3H), 2.11 (s, 3H), I .85(d, J7.2 H, 3H).

Reference： [1]Patent: WO2013/120104,2013,A2 .Location in patent: Paragraph 00329; 00332

48
[ 459-47-2 ]
[ 65130-46-3 ]

Yield	Reaction Conditions	Operation in experiment
80%	With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; at 80℃; for 5h;	(±)4(14romoethyI)41uorobenzene.A mixture of 1-ethyi-4-fluorohenzene (0248g, 2mmol), NBS (0.35g. 2mmol) and benzoyl peroxide (0. 14g, 0.6mmoi) were dissolved in 20 mL Cd4, The mixture was stirred at 0 °C for 5 hours and then the reaction was cone. in vacuo and resulting oil was purified via silica gel chromatography (PE-EtOAC 5: 1) to give the title compound (330 mg, 80percent) as a yellow oil. LCMS 202 (M ± Hj.

Reference： [1]Patent: WO2013/120104,2013,A2 .Location in patent: Paragraph 00330

49
[ 65130-46-3 ]
[ 403-41-8 ]

Reference： [1]RSC Advances,2014,vol. 4,p. 49974 - 49978

50
N-[2-(3,5-dichloropyridin-2-yl)-2-(hydroxyimino)ethyl]-2-(trifluoromethyl)benzamide [ No CAS ]
[ 65130-46-3 ]
N-[2-(3,5-dichloropyridin-2-yl)-2-[1-(4-fluorophenyl)ethoxyimino]ethyl]-2-(trifluoromethyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
171 mg	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 18h;	To a suspension of 200 mg of N-[2-(3,5-dichloropyridin-2-yl)-2-(hydroxyimino)ethyl]-2-(trifluoromethyl)benzamide and 211 mg of potassium carbonate in 2 ml of N,N-dimethylformamide, 155 mg of <strong>[65130-46-3]1-(1-bromoethyl)-4-fluorobenzene</strong> was added, and the mixture was stirred at room temperature for 18 hours. After completion of the reaction, the reaction mixture was mixed with 3 ml of water and extracted with ethyl acetate (3 mlx2), the resulting organic layers were combined, washed with water (3 ml*1) and dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography using ethyl acetate-hexane (with a gradient of from 5:95 to 50:50) as the eluent to obtain 171 mg of the desired product as a pale yellow resinous substance. 1H NMR (CDCl3, Me4Si, 300MHz) delta8.52 and 8.42 (d, J=2.1 Hz, 1 H), 7.80 and 7.77 (d, J=2.1 Hz, 1 H), 6.0-7.75 (m, 8H), 6.40 (bs, 1 H), 5.38 and 5.21 (q, J=6.9Hz, 1 H), 4.81 and 4.49 (d, J=5.7Hz, 2H), 1.64 and 1.45 (d, J=6.9Hz, 3H).
171 mg	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 18h;	To a suspension of 200 mg of N-[2-(3,5-dichloropyridin-2-yl)-2-(hydroxyimino)ethyl]-2-(trifluoromethyl)benzamide and 211 mg of potassium carbonate in 2 ml of N,N-dimethylformamide, 155 mg of <strong>[65130-46-3]1-(1-bromoethyl)-4-fluorobenzene</strong> was added, and the mixture was stirred at room temperature for 18 hours. After completion of the reaction, the reaction mixture was mixed with 3 ml of water and extracted with ethyl acetate (3 ml×2), the resulting organic layers were combined, washed with water (3 ml×1) and dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography using ethyl acetate-hexane (with a gradient of from 5:95 to 50:50) as the eluent to obtain 171 mg of the desired product as a pale yellow resinous substance

Reference： [1]Patent: EP2873658,2015,A1 .Location in patent: Paragraph 0480
[2]Patent: JP2016/11286,2016,A .Location in patent: Paragraph 0515

51
[ 405-99-2 ]
[ 332-42-3 ]
[ 65130-46-3 ]

Reference： [1]Organic and Biomolecular Chemistry,2016,vol. 14,p. 5622 - 5626

52
[ 6783-05-7 ]
[ 65130-46-3 ]
[ 1236889-31-8 ]

Reference： [1]Journal of the American Chemical Society,2016,vol. 138,p. 10774 - 10777

53
[ 65130-46-3 ]
3-(4-fluorophenyl)-1-phenylbutan-1-one [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 9969 - 9973
Angew. Chem.,2016,vol. 128,p. 10123 - 10127,5

54
[ 2564-83-2 ]
[ 65130-46-3 ]
1-(1-(4-fluorophenyl)ethoxy)-2,2,6,6-tetramethylpiperidine [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2016,vol. 55,p. 9969 - 9973
Angew. Chem.,2016,vol. 128,p. 10123 - 10127,5

55
[ 14531-55-6 ]
[ 65130-46-3 ]
(±)-1-[1-(4-fluorophenyl)ethyl]-3,5-dimethyl-4-nitro-1H-pyrazole [ No CAS ]

Reference： [1]ChemMedChem,2016,vol. 11,p. 2261 - 2271

56
[ 65130-46-3 ]
(±)-6-bromo-N-{1-[1-(4-fluorophenyl)ethyl]-3,5-dimethyl-1H-pyrazol-4-yl}-2-(trifluoromethyl)quinoline-4-carboxamide [ No CAS ]

Reference： [1]ChemMedChem,2016,vol. 11,p. 2261 - 2271

57
[ 65130-46-3 ]
(±)-1-[1-(4-fluorophenyl)ethyl]-3,5-dimethyl-1H-pyrazol-4-amine [ No CAS ]

Reference： [1]ChemMedChem,2016,vol. 11,p. 2261 - 2271

58
C₂₈H₄₂N₆O₈ [ No CAS ]
[ 65130-46-3 ]
C₃₆H₄₉FN₆O₈ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 3212 - 3216

59
[ 1826-67-1 ]
[ 65130-46-3 ]
C₁₀H₁₁F [ No CAS ]

Reference： [1]Organic Letters,2017,vol. 19,p. 6590 - 6593

60
[ 65130-46-3 ]
(Z)-2-(3-(4-fluorophenyl)but-2-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane [ No CAS ]

Reference： [1]Organic Letters,2017,vol. 19,p. 6590 - 6593

61
[ 65130-46-3 ]
(R)-1-(1-(4-fluorophenyl)ethyl)-4-nitro-1H-pyrazole [ No CAS ]

Reference： [1]Patent: WO2018/148626,2018,A1

62
[ 65130-46-3 ]
(R)-1-(1-(4-fluorophenyl)ethyl)-1H-pyrazol-4-amine [ No CAS ]
(S)-1-(1-(4-fluorophenyl)ethyl)-1H-pyrazol-4-amine [ No CAS ]

Reference： [1]Patent: WO2018/148626,2018,A1

63
[ 2075-46-9 ]
[ 65130-46-3 ]
1-(1-(4-fluorophenyl)ethyl)-4-nitro-1H-pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With sodium hexamethyldisilazane; In tetrahydrofuran; at 20℃;	mg, 4.42 mmol) in DMF (10 mL) was added 1.0 M NaHMDS/THF (4.86 mL, 4.86 mmol) dropwise at rt. After stirring at rt for 20 min, l-(1-bromoethyl)-4-fluorobenzene (1077 mg, 5.31 mmol) was added very slowly. The mixture was stirred at rt for 3 h. EtOAc was added and the organics washed with water. The organics were collected, dried over sodium sulfate and concentrated under vacuum. The residue was purified via silica gel chromatography (24g, hexanes-50%EtOAc) to give l-(1-(4-fluorophenyl)ethyl)-4-nitro-1H-pyrazole (980 mg, 4.17 mmol, 94 % yield). NMR (499 MHz, CDC13) delta 8.12 (s, 1H), 8.09 (s, 1H), 7.33-7.27 (m, 2H), 7.14-7.08 (m, 2H), 5.53 (q, J=7.1Hz, 1H), 1.95 (d, J=7.0 Hz, 3H).
94%		To a solution of 4-nitro- 1H-pyrazole (500 mg, 4.42 mmol) in DMF (10 mL) was added 1.0 M NaHMDS/THF (4.86 mL, 4.86 mmol) dropwise at rt. After stirring at rt for 20 min, 1-(1-bromoethyl)-4- fluorobenzene (1077 mg, 5.31 mmol) was added very slowly. The mixture was stirred at rt for 3 h. EtOAc was added. The organic layer was washed with water and concentrated in vacuo. The residue was purified via silica gel chromatography (24g, hexanes- 50percentEtOAc) to give 1-(1-(4-fluorophenyl)ethyl)-4-nitro-1H-pyrazole (980 mg, 4.17 mmol, 94 percent yield). (2309) 1H NMR (499 MHz, CDCl3) delta 8.13 - 8.11 (m, 1H), 8.10 - 8.09 (m, 1H), 7.32 - 7.29 (m, 2H), 7.11 (s, 2H), 5.56 - 5.50 (m, 1H), 1.95 (d, J=7.0 Hz, 3H).
81%	With potassium carbonate; In N,N-dimethyl-formamide; at 23℃; for 2h;	To a solution of4-nitro-1H-pyrazole (25 mg, 0.221 mmol) and potassium carbonate (36.7 mg, 0.265 mmol) in DMF (1 mL) was added <strong>[65130-46-3]1-(1-bromoethyl)-4-fluorobenzene</strong> (44.9 mg, 0.221 mmol) at 23 C and stirred for 2 h. The reaction mixture was purified by column chromatography on the Isco system (12 g, 0-50% EtOAc/Hex) to yield 1-(1-(4-fluorophenyl)ethyl)-4-nitro-1H-pyrazole as the racemate. (42 mg, 0. 179mo1, 81%).?H NMR (400 MHz, CD3OD) oe 8.66 (s, 1H), 8.14 (s, 1H), 7.44 - 7.37 (m, 2H), 7.15 - 7.07 (m, 2H), 5.67 (q, J7.0 Hz, 1H), 1.92 (d, J=7.1 Hz, 3H).MS ESI m/z 236.1 (M+H).

Reference： [1]Patent: WO2019/89442,2019,A1 .Location in patent: Page/Page column 202
[2]Patent: WO2019/147782,2019,A1 .Location in patent: Page/Page column 750
[3]Patent: WO2018/148626,2018,A1 .Location in patent: Page/Page column 152

64
[ 65130-46-3 ]
[ 1109230-28-5 ]

Reference： [1]Patent: US2010/197725,2010,A1

65
[ 65130-46-3 ]
[ 1109230-23-0 ]

Reference： [1]Patent: US2010/197725,2010,A1

66
[ 65130-46-3 ]
[ 1109230-29-6 ]

Reference： [1]Patent: US2010/197725,2010,A1

67
[ 65130-46-3 ]
{4-[R-(4-fluoro-phenyl)-ethyl]-2R-methyl-piperazin-1-yl}-(6-methoxy-1H-pyrrolo[2,3-b]pyridin-5-yl)-methanone [ No CAS ]

Reference： [1]Patent: WO2006/112828,2006,A1

68
[ 65130-46-3 ]
2-(5-{4-[1R-(4-fluoro-phenyl)-ethyl]-2R-methyl-piperazine-1-carbonyl}-6-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)-N-methyl-2-oxo-acetamide [ No CAS ]

Reference： [1]Patent: WO2006/112828,2006,A1

69
[ 65130-46-3 ]
[ 672293-90-2 ]

Reference： [1]Patent: WO2006/112828,2006,A1

70
ethyl 2-(4-(2H-tetrazol-5-yl)phenylsulfonamido)acetate [ No CAS ]
[ 65130-46-3 ]
ethyl 2-(4-(2-(1-(4-fluorophenyl)ethyl)-2H-tetrazol-5-yl)phenylsulfonamido)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%	With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 85℃; for 16h;	To a solution of ethyl 2-(4-(2H-tetrazol-5-yl)phenylsulfonamido)acetate (500 mg, 0.0016 mol, Intermediate 115) in acetonitrile (10 mL), /VJv-diisopropylethylamine (0.7 mL, 0.0040 mol, commercial source: Finar) and <strong>[65130-46-3]1-(1-bromoethyl)-4-fluorobenzene</strong> (389 mg, 0.0019 mol, Intermediate 142) was added at 26 °C and the mixture stirred at 85 °C for 16 h. Upon completion, it was cooled to 26 °C and dissolved in ethyl acetate (100 mL) and water (20 mL). The organic layer was separated, dried over Na2S04, filtered and concentrated under reduced pressure. The crude was purified by column chromatography (silicagel 100-200 mesh), eluted with 1 .5percent methanol in dichloromethane. The pure fractions were collected and concentrated under reduced pressure to afford ethyl 2-(4-(2-(1-(4-fluorophenyl)ethyl)-2H-tetrazol-5- yl)phenylsulfonamido)acetate (300 mg, 41 percent) as an off white solid. MS m/z [M+H]+= 434.26.

Reference： [1]Patent: WO2019/34729,2019,A1 .Location in patent: Page/Page column 106

71
[ 65130-46-3 ]
2-(4-(2-(1-(4-fluorophenyl)ethyl)-2H-tetrazol-5-yl)phenylsulfonamido)acetic acid [ No CAS ]

Reference： [1]Patent: WO2019/34729,2019,A1

72
[ 65130-46-3 ]
tert-butyl (2-amino-2-oxoethyl)((4-(2-(1-(4-fluorophenyl)ethyl)-2H-tetrazol-5-yl)-2-methoxyphenyl)sulfonyl)carbamate [ No CAS ]

Reference： [1]Patent: WO2019/34729,2019,A1

73
[ 65130-46-3 ]
2-(4-(2-(1-(4-fluorophenyl)ethyl)-2H-tetrazol-5-yl)phenylsulfonamido)acetamide [ No CAS ]
2-(4-(2-(1-(4-fluorophenyl)ethyl)-2H-tetrazol-5-yl)phenylsulfonamido)acetamide [ No CAS ]

Reference： [1]Patent: WO2019/34729,2019,A1

74
[ 65130-46-3 ]
2-(4-(2-(1-(4-fluorophenyl)ethyl)-2H-tetrazol-5-yl)-2-methoxyphenylsulfonamido)acetamide [ No CAS ]
2-(4-(2-(1-(4-fluorophenyl)ethyl)-2H-tetrazol-5-yl)-2-methoxyphenylsulfonamido)acetamide [ No CAS ]

Reference： [1]Patent: WO2019/34729,2019,A1

75
N-(2-hydroxyethyl)-4-(2H-tetrazol-5-yl)benzenesulfonamide [ No CAS ]
[ 65130-46-3 ]
4-(2-(1-(5-fluoropyridin-2-yl)ethyl)-2H-tetrazol-5-yl)-N-(2-hydroxyethyl)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
26%	With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 85℃; for 16h;	To a solution of N-(2-hydroxyethyl)-4-(2H-tetrazol-5-yl)benzenesulfonamide (300 mg, 0.001 1 mol, intermediate 17) and /V,/V-diisopropylethylamine (0.38 mL, 0.0022 mol, commercial source: Finar) in acetonitrile (6 mL), 1 -(1 -bromoethyl)-4-fluorobenzene (271 mg, 0.0013 mol, Intermediate 142) was added at 26°C. The reaction mixture was heated to 85°C and stirred for 16 h at the same temperature. Upon completion, the reaction mixture was cooled to 26°C, dissolved in ethyl acetate (10 mL) and washed with water (30 mL) and brine (40 mL). The organic layer was dried over Na2S04, filtered and concentrated under reduced pressure. The crude was purified by column chromatography (silicagel 100-200 mesh), eluted with 1.5percent methanol in dichloromethane. The pure fractions were collected and concentrated under reduced pressure to afford (4-(2-(1 -(5-fluoropyridin-2-yl)ethyl)-2H-tetrazol-5-yl)-N-(2- hydroxyethyl)benzenesulfonamide (1 10 mg, 26percent) as an off white solid.The obtained racemic compound was submitted to chiral prep-SFC for the separation of isomers.SFC prep Conditions:Column: Chiralpak IG (30x250mm), 5mupercentC02: 55percent: percentco-solvent: 45percent (100percent methanol)Flow: 90g/mm, Back pressure: 90bar, UV: 254nm, Stack time: 5.5mnLoading: 8.6 mg, Solubility: MeOH, No. of inj: 20Instrument model: Make/model: SFC-200-002The two pure fractions were dried under lyophilization to afford:Isomer 1 : (43 mg, 10percent) as a brown gummy solid and as a single unknown enantiomer.1H NMR (400 MHz, DMSO-de) delta 8.24 (d, J=8.1 Hz, 2H), 7.96 (d, J=8.3 Hz, 2H), 7.52-7.49 (m, 2H), 7.26-7-21 (m, 2H), 6.44-6.39 (m, 1 H), 3.38-3.35 (m, 2H), 2.85-2.82 (m, 2H), 2.02 (d, J=7 Hz, 3H). MS m/z [M+H]+= 392.05, chiral purity: eepercent = 99.53percent. Isomer 2: (49 mg, 1 1 percent) as a brown gummy solid and as a single unknown enantiomer.1H NMR (400 MHz, DMSO-d6) delta 8.25 (d, J=8.3 Hz, 2H), 7.97 (d, J=8.3 Hz, 2H), 7.76-7.73 (m, 1 H), 7.52-7.49 (m, 2H), 7.26-7-21 (m, 2H), 6.44-6.39 (m, 1 H), 4.67-4.64 (m, 1 H), 3.39-3.34 (m, 2H), 2.86-2.81 (m, 2H), 2.03-2.01 (m, 3H). MS m/z [M+H]+= 392.02, chiral purity: eepercent = 99.80percent

Reference： [1]Patent: WO2019/34729,2019,A1 .Location in patent: Page/Page column 172

76
N-(2-hydroxyethyl)-4-(2H-tetrazol-5-yl)benzenesulfonamide [ No CAS ]
[ 65130-46-3 ]
4-(2-(1-(5-fluoropyridin-2-yl)ethyl)-2H-tetrazol-5-yl)-N-(2-hydroxyethyl)benzenesulfonamide [ No CAS ]
4-(2-(1-(5-fluoropyridin-2-yl)ethyl)-2H-tetrazol-5-yl)-N-(2-hydroxyethyl)benzenesulfonamide [ No CAS ]

Reference： [1]Patent: WO2019/34729,2019,A1

77
2-methoxy-4-(2H-tetrazol-5-yl)benzenesulfonamide [ No CAS ]
[ 65130-46-3 ]
4-(2-(1-(4-fluorophenyl)ethyl)-2H-tetrazol-5-yl)-2-methoxybenzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
27%	With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 85℃; for 16h;	To a solution of ethyl 2-(4-(2H-tetrazol-5-yl)phenylsulfonamido)acetate (1.2 g, 0.0047 mol, Intermediate 51 ) and <strong>[65130-46-3]1-(1-bromoethyl)-4-fluorobenzene</strong> (1 .14 g, 0.0056 mol, Intermediate 142) in acetonitrile (24 mL), /VJv-diisopropylethylamine (2.0 mL, 0.01 18 mol, commercial source: Finar) was added at 26 °C and the mixture stirred at 85 °C for 16 h. Upon completion, it was cooled to 26 °C and dissolved in ethyl acetate (100 mL) and water (20 mL). The organic layer was separated, dried over Na2S04, filtered and concentrated under reduced pressure. The crude was purified by column chromatography (silicagel 100-200 mesh), eluted with 1 percent methanol in dichloromethane. The pure fractions were collected and concentrated under reduced pressure to afford 4-(2-(1-(4- fluorophenyl)ethyl)-2H-tetrazol-5-yl)-2-methoxybenzenesulfonamide (500 mg, 27percent) as an off white solid. MS m/z [M+H]+= 378.52

Reference： [1]Patent: WO2019/34729,2019,A1 .Location in patent: Page/Page column 107

78
[ 65130-46-3 ]
1-(1-(4-fluorophenyl)ethyl)-1H-pyrazol-4-amine [ No CAS ]

Reference： [1]Patent: WO2019/89442,2019,A1
[2]Patent: WO2019/147782,2019,A1

79
[ 1036378-83-2 ]
[ 65130-46-3 ]
1,3-diphenyl-5-(1-(4-fluorophenyl)ethyl)benzene [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2020,vol. 142,p. 19652 - 19659

80
[ 65130-46-3 ]
[ 3553-12-6 ]
C₁₃H₁₄FN₃O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With potassium carbonate In dichloromethane at 50℃; for 6h;	8.A A suspension of compound 9-1 (1.50 g, 11.99 mmol) and compound 10-6 (2.68 g, 13.19 mmol) in dichloromethane (50 mL) was treated with potassium carbonate (2.49 g, 17.99 mmol), and then the mixture Heat to 50°C and keep at this temperature for 6h. The mixture was cooled to 25°C, and the insoluble matter was filtered off. The supernatant was concentrated and purified by column chromatography (0% to 50% ethyl acetate/petroleum ether) to obtain pure product 11-4 (2.34g, 79%):

Reference： [1]Current Patent Assignee: TIANJIN INST PHARMACEUTICAL - CN113493442, 2021, A Location in patent: Paragraph 0207-0210

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Ghs Precautionary Statements

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

Ghs Hazard Statements

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