[ CAS No. 60811-17-8 ] {[proInfo.proName]}

Name: 60811-17-8|5-Bromo-2-chloroaniline|98%
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Quality Control of [ 60811-17-8 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 60811-17-8 ]

Product Details of [ 60811-17-8 ]

CAS No. :	60811-17-8	MDL No. :	MFCD06796283
Formula :	C₆H₅BrClN	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	UGOLEPGQWYPIBR-UHFFFAOYSA-N
M.W :	206.47	Pubchem ID :	3830731
Synonyms :

Calculated chemistry of [ 60811-17-8 ]

Physicochemical Properties

Num. heavy atoms :	9
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	0.0
Num. H-bond donors :	1.0
Molar Refractivity :	43.56
TPSA :	26.02 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	Yes
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.44 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.91
Log Po/w (XLOGP3) :	2.98
Log Po/w (WLOGP) :	2.69
Log Po/w (MLOGP) :	2.84
Log Po/w (SILICOS-IT) :	2.46
Consensus Log Po/w :	2.58

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.49
Solubility :	0.0667 mg/ml ; 0.000323 mol/l
Class :	Soluble
Log S (Ali) :	-3.19
Solubility :	0.133 mg/ml ; 0.000646 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.51
Solubility :	0.0635 mg/ml ; 0.000308 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.64

Safety of [ 60811-17-8 ]

Signal Word:	Warning	Class:
Precautionary Statements:	P301+P312+P330	UN#:
Hazard Statements:	H302	Packing Group:
GHS Pictogram:

Application In Synthesis of [ 60811-17-8 ]

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

Upstream synthesis route of [ 60811-17-8 ]
Downstream synthetic route of [ 60811-17-8 ]

[ 60811-17-8 ] Synthesis Path-Upstream 1~12

1
[ 109-01-3 ]
[ 60810-77-7 ]
[ 60811-17-8 ]
[ 110-16-7 ]
[ 60811-18-9 ]

Reference： [1] Patent: US4238611, 1980, A,

2
[ 16588-24-2 ]
[ 60811-17-8 ]

Reference： [1] American Chemical Journal, 1892, vol. 14, p. 571
[2] American Chemical Journal, 1891, vol. 13, p. 425
[3] , 1967, vol. 3, p. 1795 - 1799[4] Zhurnal Organicheskoi Khimii, 1967, vol. 3, # 10, p. 1839 - 1843
[5] Patent: US4061761, 1977, A,

3
[ 16588-24-2 ]
[ 7439-89-6 ]
[ 60811-17-8 ]

Reference： [1] Patent: US2004/162282, 2004, A1,

4
[ 635-22-3 ]
[ 60811-17-8 ]

Reference： [1] , 1967, vol. 3, p. 1795 - 1799[2] Zhurnal Organicheskoi Khimii, 1967, vol. 3, # 10, p. 1839 - 1843

5
[ 112160-74-4 ]
[ 591-19-5 ]
[ 60811-17-8 ]
[ 823-54-1 ]

Reference： [1] Journal of the Chemical Society, 1901, vol. 79, p. 465

6
[ 112160-74-4 ]
[ 106-40-1 ]
[ 60811-17-8 ]
[ 823-54-1 ]

Reference： [1] Journal of the Chemical Society, 1901, vol. 79, p. 465

7
[ 67-66-3 ]
[ 112160-74-4 ]
[ 591-19-5 ]
[ 60811-17-8 ]
[ 823-54-1 ]

Reference： [1] Journal of the Chemical Society, 1901, vol. 79, p. 465

8
[ 112160-74-4 ]
[ 591-19-5 ]
[ 60811-17-8 ]
[ 823-54-1 ]

Reference： [1] Journal of the Chemical Society, 1901, vol. 79, p. 465

9
[ 112160-74-4 ]
[ 106-40-1 ]
[ 60811-17-8 ]
[ 823-54-1 ]

Reference： [1] Journal of the Chemical Society, 1901, vol. 79, p. 465

10
[ 67-66-3 ]
[ 112160-74-4 ]
[ 591-19-5 ]
[ 60811-17-8 ]
[ 823-54-1 ]

Reference： [1] Journal of the Chemical Society, 1901, vol. 79, p. 465

11
[ 60811-17-8 ]
[ 183802-98-4 ]

Reference： [1] Recueil des Travaux Chimiques des Pays-Bas, 1930, vol. 49, p. 1082,1087

12
[ 60811-17-8 ]
[ 81226-68-8 ]

Reference： [1] Journal of Medicinal Chemistry, 2012, vol. 55, # 11, p. 5467 - 5482
[2] Patent: WO2009/13348, 2009, A2, . Location in patent: Page/Page column 65-66
[3] Patent: US2009/239847, 2009, A1, . Location in patent: Page/Page column 43
[4] Patent: WO2011/94953, 2011, A1, . Location in patent: Page/Page column 49
[5] Patent: WO2011/95576, 2011, A1, . Location in patent: Page/Page column 49
[6] Patent: US2011/195979, 2011, A1, . Location in patent: Page/Page column 27
[7] Journal of Medicinal Chemistry, 2012, vol. 55, # 11, p. 5467 - 5482

[ 60811-17-8 ] Synthesis Path-Downstream 1~88

1
[ 16588-24-2 ]
[ 60811-17-8 ]

Yield	Reaction Conditions	Operation in experiment
	nickel; In methanol;	a. 5-Bromo-2-chloroaniline 90 g of <strong>[16588-24-2]5-bromo-2-chloronitrobenzene</strong> were hydrogenated in 500 ml of methanol at room temperature and under normal pressure with Raney-Nickel as catalyst and hydrogen. Colorless crystals, melting point: 47 C.

Reference： [1]American Chemical Journal,1892,vol. 14,p. 571
[2]Journal of Organic Chemistry USSR (English Translation),1967,vol. 3,p. 1795 - 1799
Zhurnal Organicheskoi Khimii,1967,vol. 3,p. 1839 - 1843
[3]Patent: US4061761,1977,A

2
[ 67-66-3 ]
[ 112160-74-4 ]
[ 591-19-5 ]
[ 60811-17-8 ]
[ 823-54-1 ]

Reference： [1]Journal of the Chemical Society,1901,vol. 79,p. 465

3
[ 112160-74-4 ]
[ 591-19-5 ]
[ 60811-17-8 ]
[ 823-54-1 ]

Reference： [1]Journal of the Chemical Society,1901,vol. 79,p. 465

4
[ 112160-74-4 ]
[ 106-40-1 ]
[ 60811-17-8 ]
[ 823-54-1 ]

Reference： [1]Journal of the Chemical Society,1901,vol. 79,p. 465

5
[ 635-22-3 ]
[ 60811-17-8 ]

Reference： [1]Journal of Organic Chemistry USSR (English Translation),1967,vol. 3,p. 1795 - 1799
Zhurnal Organicheskoi Khimii,1967,vol. 3,p. 1839 - 1843

6
[ 75-34-3 ]
[ 60811-17-8 ]
C₈H₅BrCl₄ [ No CAS ]

Reference： [1]Patent: US6359151,2002,B2 .Location in patent: Page column 82

7
[ 60811-17-8 ]
[ 98-09-9 ]
N-(5-bromo-2-chlorophenyl)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; In dichloromethane; at 0 - 20℃; for 2.5h;	5-Bromo-2-chloro-phenylamine (0.48 g) is dissolved in pyridine (6 mL) and the solution is cooled to O0C. Benzenesulfonyl chloride (0.41 g) in DCM (2 mL) is added dropwise. The solution is stirred at O0C for 30 minutes and at room temperature for 2 hours. Pyridine is removed under reduced pressure and the residue is dissolved in EtOAc. The organic layer is washed with 10% aqueous HCl, saturated NaHCO3, and brine. The organic layer is dried (MgSO4), filtered and evaporated and the crude material is recrystallized from EtO Ac/heptane to afford N-('5-bromo-2-chloro-phenyl')- benzenesulfonamide (O.62 g) as a solid. LCMS: Rtau = 3.06 minutes, MS: 346 (M+H).
	With pyridine; In dichloromethane; at 20℃; for 18h;	Step 1: N-(5-Bromo-2-chloro-phenyl)-benzenesulfonamide; To a stirring solution of 5-Bromo-2-chloroaniline (100 mg, 0.48 mmol) in DCM (5 ml) is added benzenesulfonyl chloride (280 mg, 202 ul, 1.58 mmol) and pyridine (195 ul, 2.42 mmol). The reaction mixture is stirred at room temperature for 18 hours. EtOAc (20 ml) is added and the reaction mixture is washed with 0.1m HCl (20 ml), the phases are separated and the organic portion is washed with water (3x), dried over MgStheta4, concentrated in vacuo and dried in a vacuum oven to afford the title compound.
	With pyridine; at 20℃; for 14h;Inert atmosphere;	After adding <strong>[60811-17-8]5-bromo-2-chloroaniline</strong> (3.0 g) to a round bottom flask, pyridine (15 ml) and benzenesulfonyl chloride (2.8 g) were added. The reaction system was reacted at room temperature for 14 hours under argon gas protection. After the reaction,The solvent was evaporated to dryness under reduced pressure.The organic phase was washed with water and saturated brine and dried over anhydrous sodium sulfate.The organic phase was filtered and evaporated to dryness then evaporated.The crude product is purified by column chromatography on silica gel to give compound (26).

Reference： [1]Patent: WO2006/81343,2006,A1 .Location in patent: Page/Page column 89
[2]Patent: WO2009/13348,2009,A2 .Location in patent: Page/Page column 64
[3]Patent: CN109721531,2019,A .Location in patent: Paragraph 0170-0172

8
[ 109-01-3 ]
tetrafluoroboric acid [ No CAS ]
[ 60810-77-7 ]
3 N-HCl [ No CAS ]
[ 60811-17-8 ]
[ 110-16-7 ]
[ 60811-18-9 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; boric acid; sodium nitrite; In ethanol; chloroform; hydrogen fluoride; water; benzene;	EXAMPLE 19 7-Fluoro-8-chloro-10-(4-methylpiperazino)-10,11-dihydrodibenzo(b,f)thiepine A mixture of 7-fluoro-8,10-dichloro-10,11-dihydrodibenzo(b,f)thiepine (7.48 g), 1-methylpiperazine (5.2 ml) and chloroform (7 ml) was refluxed for 7 hours. The chloroform was evaporated and the residue taken up in water (20 ml) and benzene (80 ml). The benzene solution was washed with water and shaken with 3 N-HCl (100 ml). The separated hydrochloride was filtered and added to the aqueous layer of the filtrate. The resulting suspension was made alkaline with ammonium hydroxide and the liberated base taken up in benzene. The desired product, m.p. 105-107 C. (acetone), was obtained in 74% yield (6.66 g). Its neutralization with maleic acid in ethanol, followed by addition of ether, yielded the crystalline maleate, m.p. 168-169 C. (ethanol). The required starting 7-fluoro-8,10-dichloro-10,11-dihydrodibenzo(b,f)thiepine was not described as yet in the literature. It can be prepared, e.g., from the known 2-chloro-5-bromoaniline (see B. R. Suthers et al: J. Org. Chem. 27, 447, 1962) by the following procedure: 2-Chloro-5-bromoaniline (258 g) is added to concentrated hydrochloric acid (750 ml) and the mixture is stirred at 80-90 C. until formation of a homogeneous suspension. Then, it is cooled and diazotized at 0-5 C. by dropwise addition of sodium nitrite (95.1 g) in water (330 ml) during 1 hour. The mixture is stirred for an additional 20 minutes and then a solution of fluoroboric acid (700 ml) (prepared by dissolving 264 g of boric acid in 744 ml of 40% hydrofluoric acid) is added. After 30 minutes of stirring, the separated fluoroborate was filtered, washed successively with a small amount of a fluoroboric acid solution, ethanol and ether, and dried thoroughly in air and in vacuo. The thermal decomposition of the fluoroborate is carried out in two portions. Each portion is heated in a flask with a direct flame, the internal temperature during the decomposition being 130-170 C. The distillates are combined and shaken with water (250 ml) and ether (250 ml). The ethereal layer is washed with 10% sodium hydroxide solution, 3 N-HCl and water and dried over sodium sulfate. The ether is evaporated and the residue is distilled, yielding 184.2 g (70%) of 2-chloro-5-bromofluorobenzene, b.p. 130-142 C./20 Torr.

Reference： [1]Patent: US4238611,1980,A

9
[ 16588-24-2 ]
[ 7439-89-6 ]
[ 60811-17-8 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium chloride; In methanol; water;	(2-Chloro-5-piperazin-1-yl-phenyl)-carbamic acid tert-butyl ester To 25 g (0.106 mol) of <strong>[16588-24-2]4-bromo-1-chloro-2-nitrobenzene</strong> in 400 mL of methanol was added 30 g (0.528 mol) of iron powder. The mixture was heated to 50 C., and 45 g (0.8456 mol) of ammonium chloride in 200 mL of water was slowly added. The reaction was heated to 70 C. over night, cooled to ambient temperature, and filtered through paper. The filtrate was concentrated in vacuo, the residue was dissolved in water, and this was extracted with ethyl acetate. The ethyl acetate phase was washed once each with water and brine, dried with Na2SO4, filtered, and concentrated to give 5-Bromo-2-chloroaniline.

Reference： [1]Patent: US2004/162282,2004,A1

10
[ 60811-17-8 ]
[ 108-91-8 ]
[ 1039767-39-9 ]

Yield	Reaction Conditions	Operation in experiment
	With dimethylaluminum chloride; In hexane; toluene; at 20 - 150℃; for 0.75h;Microwave irradiation;	EXAMPLE 87; N-[1-(5-Bromo-2-chlorophenyl)-2-cyclohexyl-4-hydroxy-6-oxo-1,6-dihydro-5-pyrimidinyl]carbonyl}glycine; 87a) 3-(5-Bromo-2-chlorophenyl)-2-cyclohexyl-6-hydroxy-4(3H)-pyrimidinone; 1M Dimethylaluminium chloride in hexane (2.75 mL, 2.75 mmol) was added to a stirred solution of <strong>[60811-17-8]5-bromo-2-chloroaniline</strong> (0.516 g, 2.50 mmol) and cyclohexanecarbonitrile (0.328 g, 3.00 mmol) in toluene (2 mL) and the mixture stirred for 15 min at room temperature under nitrogen, then microwaved at 150 C. for 30 min. After cooling, the solvent was removed under reduced pressure and diethyl malonate (1.52 mL, 10.0 mmol) added, followed by 2-methoxyethanol (5 mL) and methanolic sodium methoxide (2.30 mL, 10.0 mmol) and the mixture refluxed under nitrogen for 18 h, then cooled and poured into water (100 mL). The mixture was washed with ether, then acidified to pH 1 with 6M aqueous hydrochloric acid and extracted again with ethyl acetate. The extracts were washed with water, brine, dried (MgSO4) and evaporated under reduced pressure. The residue was chromatographed (silica gel, 1-9% methanol/dichloromethane) and the product triturated with ether. The solid was collected, washed with ether and dried to give the title compound (0.270 g, 28%) as a white solid. 1H NMR (400 MHz, DMSO-d6) delta ppm 0.82-1.03 (m, 2 H) 1.04-1.20 (m, 1 H) 1.31-1.47 (m, 1 H) 1.50-1.74 (m, 5 H) 1.77-1.88 (m, 1 H) 1.90-2.01 (m, 1 H) 5.35 (s, 1 H) 7.69 (d, J=8.59 Hz, 1 H) 7.78 (dd, J=8.70, 2.40 Hz, 1 H) 8.00 (d, J=2.27 Hz, 1 H) 11.60 (br. s., 1 H).

Reference： [1]Patent: US2008/171756,2008,A1 .Location in patent: Page/Page column 53

11
[ 60811-17-8 ]
[ 81226-68-8 ]

Yield	Reaction Conditions	Operation in experiment
		Step 1: 5-Bromo-2-chloro-benzenesulfonyl chloride; To a stirring solution of 2-chloro-5-bromoaniline (2 g, 9.69 mmol) in glacial acetic acid (60 ml) and cone. HCl (20 ml) at 0 C is added sodium nitrite (668 mg, 9.69 mmol) in water (8 ml). The reaction mixture is stirred at room temperature for 3 hours and then added to a solution of SO2/ACOH/CUCI2/H2O (150 ml) and stirred at room temperature for 18 hours. The reaction mixture is poured into water (800 ml) and extracted with ethyl acetate (3 x <n="67"/>100 ml). The combined organic layers are washed with water and dried over MgSO4. After filtration the solvent is removed in vacuo to afford the title compound.Preparation of the reagent SOi/AcOH/CuCli/HiO:According to the reported procedure (E. E. Gilbert, Synthesis 1969, 1-10, p6), glacial acetic acid (100 ml) vigorously stirred at room temperature is treated by bubbling SO2 gas. Once a saturated solution is achieved (approximately 10 g per 100 ml), the solution is treated with copper (II) chloride (4 g) in water (5 ml). The resulting mixture is allowed to settle to give a green solution.
		A solution of 2-chloro-5-bromoaniline (0.99 g, 4.7 mmol) in glacial acetic acid (30 ml) and concentrated HCl (10 ml) is cooled to 0 C., and a solution of sodium nitrite (0.32 g, 4.7 mmol) in water (40 ml) is added dropwise. The resulting solution is allowed to warm to room temperature and stirred for 2 hours. A solution of SO2/AcOH/CuCl2/H2O (100 ml) (the preparation of the reagent is described below) is added and the resulting bright green solution stirred at room temperature overnight. After this time, the reaction mixture is poured into water (400 ml) to give a milky liquid, which is extracted with ethyl acetate. The organic layer is washed with sat. aq. NaCl, dried (MgSO4), and concentrated in vacuo to afford 5-Bromo-2-chloro-benzenesulfonyl chloride as a cream solid, which is used crude in step 2.Preparation of the reagent SO2/AcOH/CuCl2/H2O:According to the reported procedure (E. E. Gilbert, Synthesis 1969, 1-10, p6), glacial acetic acid (100 ml) vigorously stirred at room temperature is treated by bubbling SO2 gas. Once a saturated solution is achieved (approximately 10 g per 100 ml), the solution is treated with copper (II) chloride (4 g) in water (5 ml). The resulting mixture is allowed to settle to give a green solution.
		To a stirring mixture of 5-bromo-2-chloro-phenylamine (2 g, 9.6 mmol) in 10 mL of HC1, a solution of NaN02 (0.8 g, 11.6 mmol) in 10 mL of water was added dropwise to keep the temperature below 5 C. The diazonium salt solution was added into a S02 gas saturated acetic acid solution of CuCl (0.28 g, 2.88 mmol), and the mixture was stirred at room temperature for 2h. The mixture was treated with water when the reaction was complete. The aqueous phase was extracted by ethyl acetate, and the combined organic solution was washed with water and aqueous NaHC03 solution, dried over Na2S04, and concentrated. The crude product from Sandmeyer reaction was used in the next step reaction without further purification.

5-Bromo-2-chloro-benzenesulfonyl chloride was prepared by the following procedures. To a stirring mixture of 5-bromo-2-chloro-phenylamine (2 g, 9.6 mmol) in 10 mL of HCl, a solution of NaNO2 (0.8 g, 11.6 mmol) in 10 mL of water was added dropwise to keep the temperature below 5 C. The diazonium salt solution was added into a SO2 gas saturated acetic acid solution of CuCl (0.28 g, 2.88 mmol), and the mixture was stirred at room temperature for 2 h. The mixture was treated with water when the reaction was complete. The aqueous phase was extracted by ethyl acetate, and the combined organic solution was washed with water and aqueous NaHCO3 solution, dried over Na2SO4, and concentrated. The crude product from Sandmeyer reaction was used in the next step reaction without further purification

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 5467 - 5482
[2]Patent: WO2009/13348,2009,A2 .Location in patent: Page/Page column 65-66
[3]Patent: US2009/239847,2009,A1 .Location in patent: Page/Page column 43
[4]Patent: WO2011/94953,2011,A1 .Location in patent: Page/Page column 49
[5]Patent: US2011/195979,2011,A1 .Location in patent: Page/Page column 27
[6]Journal of Medicinal Chemistry,2012,vol. 55,p. 5467 - 5482

12
[ 1253380-72-1 ]
[ 60811-17-8 ]
[ 1253380-27-6 ]

Yield	Reaction Conditions	Operation in experiment
		Example 1041-(5-Bromo-2<;:hlorophenyl)-4-[(2-chloro-4-fluorophenyl)methyl]-2,3- piperazinedione (E104)5-Bromo-2-chloroaniline (1.767 g, 8.55 mmol) was added to a solution of methyl [[(2- chloro-4-fluorophenyl)methyl](2-oxoethyl)amino](oxo)acetate (2.46 g, 8.55 mmol, prepared as described earlier) in acetic acid (40 ml) and stirred for 5 minutes. The reaction was cooled to 00C and sodium borohydride (0.34 g, 8.89 mmol) was added slowly, then stirred at 800C for 3 hours. The mixture was allowed to cool, then excess acetic acid was removed in vacuo, azeotroping with methanol. The residue was taken up in dichloromethane and washed with saturated aqueous sodium bicarbonate, then 3N citric acid (a small amount of brine was added to aid the separation). The organic layer was separated using a hydrophobic frit and reduced in vacuo. The residue was purified by flash-silica gel chromatography to yield 1-(5- bromo-2-chlorophenyl)-4-[(2-chloro-4-fluorophenyl)methyl]-2,3-piperazinedione(0.584 g) as a light yellow solid.LC/MS [M+H]+ = 446.9, retention time = 2.95 min.

Reference： [1]Patent: WO2010/125103,2010,A1 .Location in patent: Page/Page column 97-98

13
[ 60811-17-8 ]
[ 100-39-0 ]
[ 1297552-72-7 ]

Yield	Reaction Conditions	Operation in experiment
58%		Example 209AN,N-Dibenzyl-<strong>[60811-17-8]5-bromo-2-chloroaniline</strong>; Under argon, 9.69 g (242.16 mmol, 60% in mineral oil) of sodium hydride were suspended in 100 ml of THF, and the mixture was cooled to 0 C. 20.0 g (96.86 mmol) of <strong>[60811-17-8]5-bromo-2-chloro-aniline</strong>, dissolved in 50 ml of THF, were then slowly added dropwise, and the mixture was stirred at 0 C. for 30 min 39.76 g (232.47 mmol) of benzyl bromide, dissolved in 150 ml of THF, were then slowly added to the reaction mixture, and the mixture was then warmed to room temperature. The mixture was stirred at RT overnight and then carefully poured onto 150 ml of ice-water. The organic phase was separated off, and the aqueous phase was then extracted three more times with ethyl acetate. The combined organic phases were dried over sodium sulphate. After filtration, the solvent was removed under reduced pressure. Isopropanol was added to the crude product obtained, and the crystals formed were filtered off with suction and dried at 40 C. under high vacuum. This gave 14 g of the title compound. The filtrate was evaporated and the residue obtained was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 20:1). This gave a further 7.57 g of the title compound (total yield: 21.57 g, 58% of theory).LC-MS (Method 6): Rt=1.53 min; m/z=386/388 (M+H)+.

Reference： [1]Patent: US2011/130445,2011,A1 .Location in patent: Page/Page column 85

14
[ 60811-17-8 ]
[ 824-94-2 ]
[ 1297549-06-4 ]

Yield	Reaction Conditions	Operation in experiment
57%		Example 10A5-Bromo-2-chloro-N,N-bis(4-methoxybenzyl)aniline; Under argon, 5.07 g (126.93 mmol, 60%) of sodium hydride were suspended in 150 ml of THF, and the mixture was cooled to 0 C. 10.70 g (51.81 mmol) of <strong>[60811-17-8]5-bromo-2-chloroaniline</strong> dissolved in 10 ml of THF were then slowly added dropwise, and the mixture was stirred at 0 C. for 30 min. 25 g (124.34 mmol) of 4-methoxybenzyl chloride were then added to the reaction mixture, and the mixture was subsequently warmed to room temperature. The mixture was stirred at RT for 2 h and then slowly poured onto 150 ml of ice-water. The organic phase was separated off, and the aqueous phase was extracted three more times with ethyl acetate. The combined organic phases were dried over sodium sulphate. After filtration, the solvent was removed under reduced pressure. The crude product was purified chromatographically [column: Kromasil Si 6012, 350 mm×30 mm; mobile phase A: isohexane, mobile phase B: ethyl acetate; gradient: 0 min 98% A?4.65 min 98% A?13 min 87% A?13.01 min 98% A?13.28 min 98% A; flow rate: 70 ml/min; temperature: 20 C.; UV detection: 265 nm]. This gave 12.37 g (27.69 mmol, 57% of theory) of the title compound.1H-NMR (400 MHz, DMSO-d6, delta/ppm): 7.37 (1H, d), 7.26-7.19 (5H, m), 7.19-7.14 (1H, m), 6.86 (4H, d), 4.11 (4H, s), 3.71 (6H, s).LC-MS (Method 4): Rt=1.68 min; m/z=446 (M)+.

Reference： [1]Patent: US2011/130445,2011,A1 .Location in patent: Page/Page column 22

15
[ 60811-17-8 ]
[ 1297549-07-5 ]

Reference： [1]Patent: US2011/130445,2011,A1

16
[ 60811-17-8 ]
[ 1297549-08-6 ]

Reference： [1]Patent: US2011/130445,2011,A1

17
[ 60811-17-8 ]
[ 1297549-13-3 ]

Reference： [1]Patent: US2011/130445,2011,A1

18
[ 15790-87-1 ]
[ 60811-17-8 ]
[ 1297551-84-8 ]

Reference： [1]Patent: US2011/130445,2011,A1

19
[ 15790-87-1 ]
[ 60811-17-8 ]
[ 1297551-82-6 ]
[ 1297551-80-4 ]

Yield	Reaction Conditions	Operation in experiment
52.5%; 14.6%	With triethylamine;palladium diacetate; tris-(o-tolyl)phosphine; In N,N-dimethyl-formamide; at 150℃; for 6h;Inert atmosphere;	Example 166A and Example 167AMethyl 3-(3-amino-4-chlorophenyl)pent-2-enoate and methyl 3-(3-amino-4-chlorophenyl)pent-3-enoate; 16.9 ml (121 mmol) of triethylamine were added to a mixture of 5.0 g (24.2 mmol) of 5-bromo-2-chloraniline and 5.53 g (48.4 mmol) of methyl 2-pentenoate in 50 ml of DMF. Three times, the mixture was evacuated and in each case vented with argon. After addition of 544 mg (2.42 mmol) of palladium(II) acetate and 1.47 g (4.84 mmol) of tri-2-tolylphosphine, the mixture was evacuated two more times and in each case vented with argon, and the reaction mixture was then stirred at 150 C. for 6 h. After cooling, the mixture was kept at RT overnight and then added to water. The mixture was extracted three times with ethyl acetate. The organic phases were combnied, dried over magnesium sulphate, concentrated under reduced pressure and the residue was dried under high vacuum. The residue gave, by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 50:1 to 10:1), the two isomeric target products in separated form. This gave 0.85 g of methyl 3-(3-amino-4-chlorophenyl)pent-2-enoate (14.6% of theory) and 3.05 g of methyl 3-(3-amino-4-chlorophenyl)pent-3-enoate (52.5% of theory).Methyl 3-(3-amino-4-chlorophenyl)pent-2-enoate (Example 166A)LC-MS (Method 6): Rt=1.09 min; m/z=240 (M+H)+.1H-NMR (400 MHz, DMSO-d6): delta [ppm]=0.97 (t, 3H), 2.98 (q, 2H), 3.66 (s, 3H), 5.45 (s, 2H), 5.96 (s, 1H), 6.70 (dd, 1H), 6.95 (d, 1H), 7.21 (d, 1H).Methyl 3-(3-amino-4-chlorophenyl)pent-3-enoate (Example 167A)LC-MS (Method 6): Rt=1.00 min; m/z=240 (M+H)+.1H-NMR (400 MHz, DMSO-d6): delta [ppm]=1.75 (d, 3H), 3.47 (s, 2H), 3.56 (s, 3H), 5.28 (s, 2H), 5.94 (q, 1H), 6.54 (dd, 1H), 6.77 (d, 1H), 7.09 (d, 1H).

Reference： [1]Patent: US2011/130445,2011,A1 .Location in patent: Page/Page column 69

20
[ 13894-63-8 ]
[ 60811-17-8 ]
[ 1297551-77-9 ]

Reference： [1]Patent: US2011/130445,2011,A1

21
[ 13894-63-8 ]
[ 60811-17-8 ]
[ 1297551-71-3 ]
[ 1297551-73-5 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine;palladium diacetate; tris-(o-tolyl)phosphine; In N,N-dimethyl-formamide; at 150℃; for 4h;Inert atmosphere;	Example 164AMethyl 3-(3-amino-4-chlorophenyl)hex-2-enoate and methyl 3-(3-amino-4-chlorophenyl)hex-3-enoate; 33.8 ml (242.2 mmol) of triethylamine were added to a mixture of 10.0 g (48.4 mmol) of 5-bromo-2-chloraniline and 8.69 g (67.8 mmol) of methyl(2E)-hex-2-enoate in 100 ml of DMF. Three times, the mixture was evacuated and in each case vented with argon. After addition of 1.09 g (4.84 mmol) of palladium(11) acetate and 2.95 g (9.69 mmol) of tri-2-tolylphosphine, the mixture was evacuated two more times and in each case vented with argon, and the reaction mixture was then stirred at 150 C. for 4 h. After cooling, the mixture was added to water, saturated with sodium chloride and extracted three times with ethyl acetate. The combined organic phases were dried over magnesium sulphate and concentrated under reduced pressure, finally under high vacuum. The residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 50:1). This gave 7.70 g of a mixture of the two title compounds (62.7% of theory, ratio about 1.5:1 in favour of the alpha,beta-unsaturated isomer).LC-MS (Method 6): Methyl 3-(3-amino-4-chlorophenyl)hex-2-enoate: Rt=1.04 min, m/z=254 (M+H)+; methyl 3-(3-amino-4-chlorophenyl)hex-3-enoate: Rt=1.12 min, m/z=254 (M+H)+.1H-NMR (400 MHz, DMSO-d6): Methyl 3-(3-amino-4-chlorophenyl)hex-2-enoate: delta [ppm]=0.85 (t, 3H), 1.29-1.41 (m, 2H), 2.92-3.00 (m, 2H), 3.46 (s, 3H), 5.45 (s, 2H), 5.98 (s, 1H), 6.69 (dd, 1H), 6.94 (d, 1H), 7.20 (d, 1H).1H-NMR (400 MHz, DMSO-d6): Methyl 3-(3-amino-4-chlorophenyl)hex-3-enoate: delta [ppm]=1.00 (t, 3H), 2.15 (quin, 2H), 3.56 (s, 3H), 3.66 (s, 2H), 5.26-5.31 (m, 2H), 5.84 (t, 1H), 6.54 (dd, 1H), 6.79 (d, 1H), 7.09 (d, 1H).

Reference： [1]Patent: US2011/130445,2011,A1 .Location in patent: Page/Page column 68

22
[ 60811-17-8 ]
5-bromo-2-chloro-benzenesulfonic acid amide [ No CAS ]

Reference： [1]Patent: US2011/195979,2011,A1
[2]Journal of Medicinal Chemistry,2012,vol. 55,p. 5467 - 5482

23
[ 60811-17-8 ]
2-chloro-5-[(cis-5-hydroxy-1,3,3-trimethyl-cyclohexylmethyl)-amino]-benzenesulfonamide [ No CAS ]

Reference： [1]Patent: US2011/195979,2011,A1

24
[ 7223-38-3 ]
[ 60811-17-8 ]
[ 1350816-33-9 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 197 - 208

25
[ 60811-17-8 ]
[ 1226111-72-3 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 197 - 208

26
[ 60811-17-8 ]
[ 1351438-82-8 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 197 - 208

27
[ 60811-17-8 ]
C₁₂H₁₉ClN₄*ClH [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 197 - 208

28
[ 60811-17-8 ]
[ 1350816-34-0 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 197 - 208

29
[ 60811-17-8 ]
[ 1350816-04-4 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 197 - 208

30
[ 24424-99-5 ]
[ 60811-17-8 ]
[ 740806-51-3 ]

Yield	Reaction Conditions	Operation in experiment
97%	With dmap; triethylamine; In dichloromethane; at 0 - 20℃;	Step Rl: To <strong>[60811-17-8]5-bromo-2-chloroaniline</strong> (2.917 g, 14.13 mmol) in DCM (15 mL) was added triethylamine (5.91 mL, 42.4 mmol). The reaction was cooled to 0 C, and di-tert-butyl dicarbonate (3.94 mL, 16.95 mmol) was added. The reaction was warmed to ambient temp., and DMAP (1.726 g, 14.13 mmol) was added. Violent bubbling and precipitate were observed within one minute. The reaction mixture was stirred at RT for 16 hours. The product was purified by flash chromatography (DCM/Hexanes 1 : 1, R 0.61) to give 4.21 g (97% yield). XH-NMR (CDC13, 400 MHz): delta 8.43 (1H, d, J= 2.0 Hz), 7.19 (1H, d, J= 8.5 Hz), 7.09 (1H, dd, Jl = 8.5 Hz, J2 = 2.5 Hz), 6.99 (1H, s), 1.55 (9H, s).
61.22%	With dmap; triethylamine; In dichloromethane; at 0 - 20℃; for 16h;Inert atmosphere;	A solution of <strong>[60811-17-8]5-bromo-2-chloroaniline</strong> (1 g, 4.84 mmol, 1 eq), TEA (2.03 mL, 14.53 mmol, 3 eq) in DCM (6.3 mL) was cooled to 0C under an argon atmosphere, then Boc-anhydride (1 .33 mL, 5.80 mmol, 1 .2 eq) was added in a dropwise fashion at 0C and then DIMAP (0.590 g, 4.84 mmol, 1 eq) was added. Then, the reaction was allowed to warm to RT and stirred for 16 h. TLC analysis indicated formation of a non-polar spot. After 16 h, the reaction mixture was quenched with water (10 mL) and extracted with DCM (2x20 mL). The combined organic layer was washed with brine and dried over Na2S04 which was concentrated under reduced pressure to give crude product. The crude product was purified by column chromatography (silica gel, 100-200 mesh) using 1 -2% EtOAc in petroleum ether as an eluent to afford tert-butyl (5- bromo-2-chlorophenyl)carbamate (0.9 g, 61 .22%) as a bright white powder.

Reference： [1]Patent: WO2012/33736,2012,A1 .Location in patent: Page/Page column 49-50
[2]Patent: WO2019/119145,2019,A1 .Location in patent: Paragraph 00363; 00366

31
[ 60811-17-8 ]
[ 1364523-90-9 ]

Reference： [1]Patent: WO2012/33736,2012,A1

32
[ 60811-17-8 ]
[ 1364523-91-0 ]

Reference： [1]Patent: WO2012/33736,2012,A1

33
[ 60811-17-8 ]
N-(5-bromo-2-chlorophenyl)-N-[(Z)-2-bromo-3-(4-methylphenyl)prop-2-enyl]-4-methylbenzenesulfonamide [ No CAS ]

Reference： [1]Chemistry - A European Journal,2012,vol. 18,p. 5352 - 5360

34
[ 60811-17-8 ]
3-chloro-4-(4-methylphenylsulfonyl)-4,5-dihydronaphtho[3,2,1-cd]indole [ No CAS ]

Reference： [1]Chemistry - A European Journal,2012,vol. 18,p. 5352 - 5360

35
[ 60811-17-8 ]
4-(4-methylphenylsulfonyl)-4,5-dihydronaphtho[3,2,1-cd]indole [ No CAS ]

Reference： [1]Chemistry - A European Journal,2012,vol. 18,p. 5352 - 5360

36
[ 60811-17-8 ]
[ 98-59-9 ]
[ 1380159-23-8 ]

Reference： [1]Chemistry - A European Journal,2012,vol. 18,p. 5352 - 5360

37
[ 1377503-77-9 ]
[ 60811-17-8 ]
C₂₄H₁₇ClN₄O₂S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 5337 - 5349

38
[ 60811-17-8 ]
[ 1106313-73-8 ]