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[ CAS No. 2401-24-3 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}

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

DV 2D 3D

3d Animation Molecule Structure of 2401-24-3

Chemical Structure| 2401-24-3

Chemical Structure| 2401-24-3

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Quality Control of [ 2401-24-3 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 2401-24-3 ]

SDS Specification

Alternatived Products of [ 2401-24-3 ]

Product Details of [ 2401-24-3 ]

CAS No. :	2401-24-3	MDL No. :	MFCD00047830
Formula :	C₇H₈ClNO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	GBOUQGUQUUPGLO-UHFFFAOYSA-N
M.W :	157.60	Pubchem ID :	75460
Synonyms :

Calculated chemistry of [ 2401-24-3 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.14
Num. rotatable bonds :	1
Num. H-bond acceptors :	1.0
Num. H-bond donors :	1.0
Molar Refractivity :	42.35
TPSA :	35.25 Å²

Pharmacokinetics

GI absorption :	High
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) :	-6.15 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.82
Log Po/w (XLOGP3) :	1.57
Log Po/w (WLOGP) :	1.94
Log Po/w (MLOGP) :	1.75
Log Po/w (SILICOS-IT) :	1.75
Consensus Log Po/w :	1.76

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.18
Solubility :	1.03 mg/ml ; 0.00654 mol/l
Class :	Soluble
Log S (Ali) :	-1.92
Solubility :	1.89 mg/ml ; 0.012 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.77
Solubility :	0.268 mg/ml ; 0.0017 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.32

Safety of [ 2401-24-3 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302+H312-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 2401-24-3 ]

* 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 [ 2401-24-3 ]
Downstream synthetic route of [ 2401-24-3 ]

[ 2401-24-3 ] Synthesis Path-Upstream 1~9

1
[ 75-17-2 ]
[ 2401-24-3 ]
[ 13719-61-4 ]

Reference： [1] Bulletin de la Societe Chimique de France, 1966, p. 3311 - 3318

2
[ 2401-24-3 ]
[ 140-89-6 ]
[ 55690-60-3 ]

Reference： [1] Synthetic Communications, 2007, vol. 37, # 3, p. 369 - 376

3
[ 2401-24-3 ]
[ 364-62-5 ]

Reference： [1] Journal of the American Chemical Society, 2011, vol. 133, # 15, p. 6061 - 6071

4
[ 10298-80-3 ]
[ 2401-24-3 ]

Yield	Reaction Conditions	Operation in experiment
93%	With hydrazine In ethanol at 60℃; for 10 h; Inert atmosphere; Sealed tube	General procedure: To a sealed tube containing the nitro compound (0.6 mmol) and 2 mL ethanol were added 2.6–6.0 mmol of NH₂NH₂ (see Table 2) and Au/TiO₂ (100 mg, 1 wt.percent in [Au], 0.8 molpercent). The reaction was heated at 60 °C for an appropriate time (see Table 2) under an inert atmosphere. The reaction was monitored by TLC, and after completion, the slurry was filtered under pressure through a short pad of celite and silica gel to withhold the supported catalyst with the aid of ethanol or methanol (~ 5 mL). The filtrate was evaporated under vacuum to afford the corresponding amines in pure form. The spectroscopic data (¹H NMR, ¹³C NMR) of amines 1a–20a are in agreement with those previously reported [28,30,31], while the majority of them are commercially available substances. The screened catalysts Au/TiO₂, Au/Al₂O₃, and Au/ZnO (~ 1 wt.percent in Au) are commercially available (Strem Chemicals), and have an average gold crystallite size of ~ 2–3 nm.

Reference： [1] Chemistry - A European Journal, 2017, vol. 23, # 42, p. 9996 - 10000
[2] New Journal of Chemistry, 2015, vol. 39, # 7, p. 5360 - 5365
[3] Chemistry - A European Journal, 2016, vol. 22, # 13, p. 4600 - 4607
[4] Catalysis Communications, 2013, vol. 36, p. 48 - 51
[5] ACS Catalysis, 2014, vol. 4, # 10, p. 3504 - 3511
[6] Journal of Heterocyclic Chemistry, 1992, vol. 29, # 2, p. 503 - 509
[7] Journal of the American Chemical Society, 1955, vol. 77, p. 543,546
[8] Journal of the Chemical Society, 1955, p. 3475
[9] Chemische Berichte, 1958, vol. 91, p. 2089,2093
[10] Bulletin de la Societe Chimique de France, 1966, p. 3311 - 3318
[11] Chimica Therapeutica, 1969, vol. 4, p. 334 - 343
[12] Advanced Synthesis and Catalysis, 2011, vol. 353, # 8, p. 1306 - 1316
[13] Organic Process Research and Development, 2012, vol. 16, # 10, p. 1626 - 1634
[14] Patent: WO2016/33228, 2016, A1, . Location in patent: Page/Page column 47; 48
[15] Chinese Journal of Chemistry, 2016, vol. 34, # 11, p. 1135 - 1142

5
[ 1228378-20-8 ]
[ 1228378-54-8 ]
[ 2401-24-3 ]
[ 83490-71-5 ]

Reference： [1] Journal of the American Chemical Society, 2010, vol. 132, # 21, p. 7266 - 7267

6
[ 96-96-8 ]
[ 2401-24-3 ]

Reference： [1] Bulletin de la Societe Chimique de France, 1966, p. 3311 - 3318
[2] Chemistry - A European Journal, 2017, vol. 23, # 42, p. 9996 - 10000

7
[ 55905-53-8 ]
[ 2401-24-3 ]
[ 57645-49-5 ]
[ 71084-64-5 ]
[ 73942-11-7 ]

Reference： [1] Chemical and Pharmaceutical Bulletin, 1981, vol. 29, # 5, p. 1478 - 1480

8
[ 2401-24-3 ]
[ 2732-80-1 ]

Reference： [1] Chemistry - A European Journal, 2017, vol. 23, # 42, p. 9996 - 10000
[2] Journal of the American Chemical Society, 1955, vol. 77, p. 543,546

9
[ 2401-24-3 ]
[ 145742-50-3 ]

Reference： [1] Patent: US2012/46469, 2012, A1,

[ 2401-24-3 ] Synthesis Path-Downstream 1~88

1
[ 2401-24-3 ]
[ 2732-80-1 ]

Reference： [1]Chemistry - A European Journal,2017,vol. 23,p. 9996 - 10000
[2]Journal of the American Chemical Society,1955,vol. 77,p. 543,546

2
[ 2401-24-3 ]
[ 108-24-7 ]
[ 51488-87-0 ]

Yield	Reaction Conditions	Operation in experiment
97%	In water at 20℃; Sonication; Heating;	/V-(2-chloro-5-methoxyphenyl)acetamide (68) Compound 67 (4 g, 25.38 mmol) was suspended in 40 mL DI water, to which Acetic anhydride (9.6 mL, 102 mmol) was added dropwise. The reaction mixture was placed in an ultrasonication bath for 1 min, then was stirred in a water bath (50° C) for 10 min. The resulting solution was stirred overnight at rt. After which, the solid was collected via vacuum filtration and washed with small portions of DI water. The product was left in the funnel and air dried overnight to afford compound 68 (4.91 g, 97%) as a white solid, which was used for the next step without further purification.
97%	In water at 20 - 50℃; Sonication;	LGW-05-39 /V-(2-chloro-5-methoxyphenyl)acetamide (68). Compound 67 (4 g, 25.38 mmol) was suspended in 40 mL Dl water, to which Acetic anhydride (9.6 mL, 102 mmol) was added dropwise. The reaction mixture was placed in an ultrasonication bath for 1 min, then was stirred in a water bath (50° C) for 10 min. The resulting solution was stirred overnight at rt. After which, the solid was collected via vacuum filtration and washed with small portions of Dl water. The product was left in the funnel and air dried overnight to afford compound 68 (4.91 g, 97%) as a white solid, which was used for the next step without further purification.

Reference： [1]Current Patent Assignee: OREGON HEALTH & SCIENCE UNIVERSITY - WO2020/23911, 2020, A2 Location in patent: Page/Page column 85
[2]Current Patent Assignee: OREGON STATE BOARD OF HIGHER EDUCATION - WO2020/33435, 2020, A1 Location in patent: Paragraph 0291-0292
[3]Cummins; Tomlinson [Journal of the Chemical Society, 1955, p. 3475]

3
[ 10298-80-3 ]
[ 2401-24-3 ]

Yield	Reaction Conditions	Operation in experiment
98%	With iron; ammonium chloride In ethanol; water at 95℃; for 12h;
96%	With bis(1,5-cyclooctadiene)diiridium(I) dichloride; 1,10-Phenanthroline; isopropyl alcohol; potassium hydroxide at 100℃; for 15h; Inert atmosphere; Schlenk technique;
95%	With maghemite; methylhydrazine In ethanol at 60℃; for 1h; Sealed tube; Inert atmosphere; chemoselective reaction;

93%	With hydrazine In ethanol at 60℃; for 10h; Inert atmosphere; Sealed tube; chemoselective reaction;	2.1 General procedure of nitro compounds reduction by hydrazine catalyzed by Au/TiO₂ General procedure: To a sealed tube containing the nitro compound (0.6 mmol) and 2 mL ethanol were added 2.6-6.0 mmol of NH2NH2 (see Table 2) and Au/TiO2 (100 mg, 1 wt.% in [Au], 0.8 mol%). The reaction was heated at 60 °C for an appropriate time (see Table 2) under an inert atmosphere. The reaction was monitored by TLC, and after completion, the slurry was filtered under pressure through a short pad of celite and silica gel to withhold the supported catalyst with the aid of ethanol or methanol (~ 5 mL). The filtrate was evaporated under vacuum to afford the corresponding amines in pure form. The spectroscopic data (1H NMR, 13C NMR) of amines 1a-20a are in agreement with those previously reported [28,30,31], while the majority of them are commercially available substances. The screened catalysts Au/TiO2, Au/Al2O3, and Au/ZnO (~ 1 wt.% in Au) are commercially available (Strem Chemicals), and have an average gold crystallite size of ~ 2-3 nm.
93%	With sodium tetrahydroborate In ethanol at 20℃; for 3h; chemoselective reaction;
90%	With [Co(κS,N-4-(trifluoromethyl)pyrimidine-2-thiolate)₃]; methylhydrazine In methanol at 70℃; for 4h; Sealed tube;
88%	With hydrogen In ethanol for 24h; Ambient temperature;
44%	With sodium tetrahydroborate In water at 20℃; for 3.5h;
	With hydrogenchloride; tin(ll) chloride
	With hydrogenchloride; iron
	With ethanol; nickel Hydrogenation;
	With hydrogenchloride; tin(ll) chloride
	With hydrogen In ethanol
	With hydrogen In methanol at 20℃; for 0.5h; chemoselective reaction;
40.49 g	With iron; acetic acid at 100℃; for 1h;
	With iron; ammonium chloride In ethanol; water at 80℃; for 3h;	1.1 2-Chloro-5-methoxyaniline (2) To a mixture of 1-chloro-4-methoxy-2-nitrobenzene (1 , 40 g, 213 mmol) and ammonium chloride (45.6 g, 853 mmol) in ethanol (500 mL) and water (100 ml) was slowly added iron powder (47.6 g, 853 mmol) in portions at 80 °C. The mixture was stirred at reflux temperature for 3 h. After the starting material was consumed, the reaction mixture was concentrated under reduced pressure and the residue was diluted with ethyl acetate (200 mL), filtered and the filtrate was washed with saturated brine solution. The organic phase was dried over anhydrous sodium sulfate, concentrated in vacuo to give the title compound which was used in the next step without further purification.
	With sodium dithionite In tetrahydrofuran; water at 20℃;
	With iron; acetic acid at 20 - 90℃; for 0.5h; Inert atmosphere;

Reference： [1]Miyaji, Ryota; Asano, Keisuke; Matsubara, Seijiro [Chemistry - A European Journal, 2017, vol. 23, # 42, p. 9996 - 10000]
[2]Chen, Shujie; Lu, Guoping; Cai, Chun [New Journal of Chemistry, 2015, vol. 39, # 7, p. 5360 - 5365]
[3]Papadas, Ioannis T.; Fountoulaki, Stella; Lykakis, Ioannis N.; Armatas, Gerasimos S. [Chemistry - A European Journal, 2016, vol. 22, # 13, p. 4600 - 4607]
[4]Gkizis, Petros L.; Stratakis, Manolis; Lykakis, Ioannis N. [Catalysis Communications, 2013, vol. 36, p. 48 - 51]
[5]Fountoulaki, Stella; Daikopoulou, Vassiliki; Gkizis, Petros L.; Tamiolakis, Ioannis; Armatas, Gerasimos S.; Lykakis, Ioannis N. [ACS Catalysis, 2014, vol. 4, # 10, p. 3504 - 3511]
[6]Ioannou, Dimitris I.; Gioftsidou, Dimitra K.; Tsina, Vasiliki E.; Kallitsakis, Michael G.; Hatzidimitriou, Antonios G.; Terzidis, Michael A.; Angaridis, Panagiotis A.; Lykakis, Ioannis N. [Journal of Organic Chemistry, 2021, vol. 86, # 3, p. 2895 - 2906]
[7]Horaguchi, Takaaki; Hasegawa, Kohei; Hasegawa, Eietsu; Shimizu, Takahachi; Tanemura, Kiyoshi; Suzuki, Tsuneo [Journal of Heterocyclic Chemistry, 1992, vol. 29, # 2, p. 503 - 509]
[8]Wang, Gang; Yuan, Shuo; Wu, Zhiqiang; Liu, Wanyi; Zhan, Haijuan; Liang, Yanping; Chen, Xiaoyan; Ma, Baojun; Bi, Shuxian [Applied Organometallic Chemistry, 2019, vol. 33, # 11]
[9]Faith et al. [Journal of the American Chemical Society, 1955, vol. 77, p. 543,546]
[10]Cummins; Tomlinson [Journal of the Chemical Society, 1955, p. 3475]
[11]Teuber; Schnee [Chemische Berichte, 1958, vol. 91, p. 2089,2093]
[12]Munavalli,S. et al. [Bulletin de la Societe Chimique de France, 1966, p. 3311 - 3318]
[13]Julia,M.; de Rosnay,J. [Chimica Therapeutica, 1969, vol. 4, p. 334 - 343]
[14]Location in patent: scheme or table Pandarus, Valerica; Ciriminna, Rosaria; Beland, Francois; Pagliaro, Mario [Advanced Synthesis and Catalysis, 2011, vol. 353, # 8, p. 1306 - 1316]
[15]Armitage, Mark; Bret, Guillaume; Choudary, Bernie M.; Kingswood, Mike; Loft, Mike; Moore, Steve; Smith, Steve; Urquhart, Michael W. J. [Organic Process Research and Development, 2012, vol. 16, # 10, p. 1626 - 1634]
[16]Current Patent Assignee: SUNNYLIFE PHARMA - WO2016/33228, 2016, A1 Location in patent: Page/Page column 47; 48
[17]Hua, Xuewen; Zhou, Shaa; Chen, Minggui; Wei, Wei; Liu, Ming; Lei, Kang; Zhou, Sha; Li, Yonghong; Wang, Baolei; Li, Zhengming [Chinese Journal of Chemistry, 2016, vol. 34, # 11, p. 1135 - 1142]
[18]Abdelhameed, Ahmed; Liao, Xiaoping; McElroy, Craig A.; Joice, April C.; Rakotondraibe, Liva; Li, Junan; Slebodnick, Carla; Guo, Pu; Wilson, W. David; Werbovetz, Karl A. [Bioorganic and Medicinal Chemistry Letters, 2020, vol. 30, # 1]

4
[ 2401-24-3 ]
[ 2401-25-4 ]

Yield	Reaction Conditions	Operation in experiment
	(i) NaNO₂, aq. H₂SO₄, (ii) aq. KI; Multistep reaction;
	Stage #1: 2-chloro-5-methoxyaniline With sulfuric acid; acetic acid; sodium nitrite at 0℃; for 0.666667h; Stage #2: With sodium iodide In water at 60℃; for 1h;

Reference： [1]Bartle,K.D. et al. [Tetrahedron, 1965, vol. 21, p. 3289 - 3296]
[2]Nishiyama, Yutaka; Kawabata, Hiroshi; Nishino, Toshiki; Hashimoto, Kouji; Sonoda, Noboru [Tetrahedron, 2003, vol. 59, # 34, p. 6609 - 6614]

5
[ 2902-65-0 ]
[ 2401-24-3 ]
[ 98370-41-3 ]

Yield	Reaction Conditions	Operation in experiment
60%	With N-ethylmorpholine; In benzene for 2h; Heating;
	With N-ethylmorpholine;; copper(l) chloride In benzene at 120℃; for 1h;

Reference： [1]Rewcastle, Gordon W.; Denny, William A. [Synthesis, 1985, # 2, p. 217 - 220]
[2]Rewcastle, Gordon W.; Atwell, Graham J.; Chambers, David; Baguley, Bruce C.; Denny, William A. [Journal of Medicinal Chemistry, 1986, vol. 29, # 4, p. 472 - 477]

6
[ 2401-24-3 ]
[ 544-92-3 ]
[ 127667-00-9 ]

Reference： [1]Journal of Organic Chemistry,1990,vol. 55,p. 4817 - 4821

7
[ 75-17-2 ]
[ 2401-24-3 ]
[ 13719-61-4 ]

Reference： [1]Bulletin de la Societe Chimique de France,1966,p. 3311 - 3318

8
[ 553-82-2 ]
[ 7664-41-7 ]
sodium amide [ No CAS ]
petroleum ether [ No CAS ]
[ 2401-24-3 ]
[ 13726-14-2 ]
[ 95-03-4 ]

Reference： [1]Journal of the American Chemical Society,1953,vol. 75,p. 3196

9
[ 2401-24-3 ]
[ 329-15-7 ]
[ 1026518-75-1 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In tetrahydrofuran at 24℃; for 18h;

Reference： [1]Romine, Jeffrey L.; Starrett Jr., John E.; Martin, Scott W.; Gribkoff, Valentin K.; Boissard, Christopher G.; Dworetzky, Steven I.; Natale, Joanne; Li, Yi; Gao, Qi; Meanwell, Nicholas A. [Journal of Medicinal Chemistry, 2002, vol. 45, # 14, p. 2942 - 2952]

10
[ 2401-24-3 ]
[ 264208-72-2 ]
M 475271 [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With hydrogenchloride In isopropyl alcohol at 80℃;

Reference： [1]Plé, Patrick A.; Green, Tim P.; Hennequin, Laurent F.; Curwen, Jon; Fennell, Michael; Allen, Jack; Lambert-Van Der Brempt, Christine; Costello, Gerard [Journal of Medicinal Chemistry, 2004, vol. 47, # 4, p. 871 - 887]

11
[ 2401-24-3 ]
[ 622369-40-8 ]
4-[(2-chloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20%	With pyridine hydrochloride In 2-ethoxy-ethanol at 120℃; for 3h;

Reference： [1]Boschelli, Diane H.; Wang, Yanong D.; Johnson, Steve; Wu, Biqi; Ye, Fei; Barrios Sosa, Ana Carolina; Golas, Jennifer M.; Boschelli, Frank [Journal of Medicinal Chemistry, 2004, vol. 47, # 7, p. 1599 - 1601]

12
[ 2401-24-3 ]
[ 196195-13-8 ]
N-(2-chloro-5-methoxyphenyl)-6-methoxy-7-(3-morpholinopropoxy)quinazolin-4-amine dihydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With hydrogenchloride In isopropyl alcohol at 80℃; for 2.5h;

Reference： [1]Plé, Patrick A.; Green, Tim P.; Hennequin, Laurent F.; Curwen, Jon; Fennell, Michael; Allen, Jack; Lambert-Van Der Brempt, Christine; Costello, Gerard [Journal of Medicinal Chemistry, 2004, vol. 47, # 4, p. 871 - 887]

13
[ 590-28-3 ]
[ 2401-24-3 ]
[ 460346-03-6 ]

Yield	Reaction Conditions	Operation in experiment
95%	With acetic acid In water at 30 - 40℃; for 3h; Inert atmosphere;	1 Step 1. (2-chloro-5-methoxy-phenyl) urea . A solution of potassium cyanate (124 g, 1.52 mol) in water (850 mL) was added over 2 h to a solution of 2-chloro-5-methoxy-aniline (200 g, 1.27 mol) in water (100 mL) and AcOH (800 mL) at 30°C. The reaction mixture was stirred for 1 h at 40°C, and then cooled to rt. The suspension was filtered using a medium frit and rinsed with water. The resulting solid was dried in a vacuum oven at 60°C for 48 h to provide the title compound (240 g, 95%) as a solid. lH NMR (400 MHz, DMSO) δ 8.00 (s, 1H), 7.85 (d, / = 3.0 Hz, 1H), 7.27 (d, / = 8.8 Hz, 1H), 6.54 (dd, / = 8.8, 3.0 Hz, 1H), 6.42 (s, 2H), 3.71 (s, 3H). [M+H] = 201.1.
	With acetic acid

Reference： [1]Current Patent Assignee: DART NEUROSCIENCE LLC - WO2019/14305, 2019, A1 Location in patent: Page/Page column 93; 91
[2]Bernardelli, Patrick; Lorthiois, Edwige; Vergne, Fabrice; Oliveira, Chrystelle; Mafroud, Abdel-Kader; Proust, Emmanuelle; Pham, Nga; Ducrot, Pierre; Moreau, François; Idrissi, Moulay; Tertre, Anita; Bertin, Bernadette; Coupe, Magali; Chevalier, Eric; Descours, Arnaud; Berlioz-Seux, Françoise; Berna, Patrick; Li, Mei [Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 18, p. 4627 - 4631]

14
[ 2401-24-3 ]
[ 364793-57-7 ]
7-bromo-4-(2-chloro-5-methoxy-phenylamino)-quinoline-3-carbonitrile [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 1743 - 1747

15
[ 2401-24-3 ]
[ 243982-40-3 ]
<i>N</i>-(2-chloro-5-methoxy-phenyl)-3,3,3-trifluoro-2-methyl-2-trimethylsilanyloxy-propionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In dichloromethane at 0℃; for 16h;

Reference： [1]Bebernitz, Gregory R.; Aicher, Thomas D.; Stanton, James L.; Gao, Jiaping; Shetty, Suraj S.; Knorr, Douglas C.; Strohschein, Robert J.; Tan, Jennifer; Brand, Leonard J.; Liu, Charles; Wang, Wei H.; Vinluan, Christine C.; Kaplan, Emma L.; Dragland, Carol J.; DelGrande, Dominick; Islam, Amin; Lozito, Robert J.; Liu, Xilin; Maniara, Wieslawa M.; Mann, William R. [Journal of Medicinal Chemistry, 2000, vol. 43, # 11, p. 2248 - 2257]

16
[ 104-53-0 ]
[ 2401-24-3 ]
3-benzyl-6-methoxy-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With potassium acetate; XPhos In N,N-dimethyl acetamide at 120℃;

Reference： [1]Jia, Yanxing; Zhu, Jieping [Journal of Organic Chemistry, 2006, vol. 71, # 20, p. 7826 - 7834]

17
[ 438249-84-4 ]
[ 2401-24-3 ]
4-(2-Chloro-5-methoxyanilino)-2-(2-pyridinyl)-6-(trifluoromethyl)pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%	With hydrogenchloride In ethanol; water Heating;
48%		95 4-(2-Chloro-5-methoxyanilino)-2-(2-pyridinyl)-6-(trifluoromethyl)pyrimidine EXAMPLE 95 4-(2-Chloro-5-methoxyanilino)-2-(2-pyridinyl)-6-(trifluoromethyl)pyrimidine The title compound was prepared from a mixture of 4-chloro-2-(2-pyridinyl)-6-(trifluoromethyl)pyrimidine (25 mg, 0.096 mmol) and 2-chloro-5-methoxyaniline (23 mg, 0.144 mmol) similar to Example 92 and isolated as a white solid (11 mg, 48%). 1H NMR (CDCl3): 8.84-8.82 (m, 1H), 8.58-8.54 (m, 1H), 7.90-7.85 (m, 1H), 7.66 (s, 1H), 7.60 (s, 1H), 7.46-7.41 (m, 1H), 7.37 (d, J=8.7 Hz, 1H), 7.01 (s, 1H), 6.75 (dd, J=3.0, 8.7 Hz, 1H), 3.88 (s, 3H).

Reference： [1]Sirisoma, Nilantha; Kasibhatla, Shailaja; Nguyen, Bao; Pervin, Azra; Wang, Yang; Claassen, Gisela; Tseng, Ben; Drewe, John; Cai, Sui Xiong [Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 23, p. 7761 - 7773]
[2]Current Patent Assignee: IMMUNE PHARMACEUTICALS INC - US2003/69239, 2003, A1

18
[ 2401-24-3 ]
[ 140-89-6 ]
[ 55690-60-3 ]

Reference： [1]Synthetic Communications,2007,vol. 37,p. 369 - 376

19
[ 2401-24-3 ]
[ 192314-71-9 ]
(2S)-2-(di-tert-butoxycarbonylamino)-3-(6-methoxy-1H-indol-3-yl)propionic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With potassium acetate; XPhos In N,N-dimethyl acetamide at 120℃;

Reference： [1]Jia, Yanxing; Zhu, Jieping [Journal of Organic Chemistry, 2006, vol. 71, # 20, p. 7826 - 7834]

20
[ 884340-91-4 ]
[ 2401-24-3 ]
[ 692726-14-0 ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 6465 - 6488

21
[ 2401-24-3 ]
[ 179246-14-1 ]
(2-chloro-5-methoxy-phenyl)-(5-methoxy-quinazolin-4-yl)-amine; compound with GENERIC INORGANIC NEUTRAL COMPONENT [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With hydrogenchloride In isopropyl alcohol at 80℃; for 0.5h;

Reference： [1]Hennequin, Laurent F.; Allen, Jack; Breed, Jason; Curwen, Jon; Fennell, Michael; Green, Tim P.; Lambert-Van Der Brempt, Christine; Morgentin, Rémy; Norman, Richard A.; Olivier, Annie; Otterbein, Ludovic; Plé, Patrick A.; Warin, Nicolas; Costello, Gerard [Journal of Medicinal Chemistry, 2006, vol. 49, # 22, p. 6465 - 6488]

22
[ 2401-24-3 ]
[ 74213-32-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 13 steps 1: 63 percent 3: 6 n HCl 4: 96 percent / liquid HF 5: 98 percent / HBr, HOAc / Ambient temperature 6: 75 percent / H₂ / Pd/C / H₂O; methanol 7: SOCl₂ 8: 85 percent / H₂ / Pd / toluene 9: 82 percent / Pb(OAc)2 / tetrahydrofuran 10: NaH / dioxane 11: NaH / dimethylformamide 12: various solvent(s) / 1 h / 50 °C 13: 44 percent / NaH, O₂ / tetrahydrofuran; dimethylformamide
	Multi-step reaction with 13 steps 1: 63 percent 3: 6 n HCl 4: 96 percent / liquid HF 5: 98 percent / HBr, HOAc / Ambient temperature 6: 75 percent / H₂ / Pd/C / H₂O; methanol 7: SOCl₂ 8: 85 percent / H₂ / Pd / toluene 9: 82 percent / Pb(OAc)2 / tetrahydrofuran 10: NaH / dioxane 11: NaH / dimethylformamide 12: various solvent(s) / 1 h / 50 °C 13: 44 percent / NaH, O₂ / tetrahydrofuran; dimethylformamide
	Multi-step reaction with 12 steps 1: 63 percent 3: 6 n HCl 4: 96 percent / liquid HF 5: 98 percent / HBr, HOAc / Ambient temperature 6: 75 percent / H₂ / Pd/C / H₂O; methanol 7: SOCl₂ 8: 85 percent / H₂ / Pd / toluene 9: 82 percent / Pb(OAc)2 / tetrahydrofuran 10: NaH / dioxane 11: NaH / dimethylformamide 12: 44 percent / NaH, O₂ / tetrahydrofuran; dimethylformamide

Reference： [1]Kirchlechner; Rogalski [Tetrahedron Letters, 1980, vol. 21, # 3, p. 247 - 250]
[2]Kirchlechner; Rogalski [Tetrahedron Letters, 1980, vol. 21, # 3, p. 247 - 250]
[3]Kirchlechner; Rogalski [Tetrahedron Letters, 1980, vol. 21, # 3, p. 247 - 250]

23
[ 2401-24-3 ]
(5aR,6aR,7R,10aR)-7-[(Ethylsulfanyl-phenyl-methyl)-amino]-1,8,10a,11-tetrahydroxy-10,12-dioxo-6,6a,7,10,10a,12-hexahydro-5aH-5-thia-naphthacene-9-carboxylic acid amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 14 steps 1: 63 percent 3: 6 n HCl 4: 96 percent / liquid HF 5: 98 percent / HBr, HOAc / Ambient temperature 6: 75 percent / H₂ / Pd/C / H₂O; methanol 7: SOCl₂ 8: 85 percent / H₂ / Pd / toluene 9: 82 percent / Pb(OAc)2 / tetrahydrofuran 10: NaH / dioxane 11: NaH / dimethylformamide 12: various solvent(s) / 1 h / 50 °C 13: 44 percent / NaH, O₂ / tetrahydrofuran; dimethylformamide
	Multi-step reaction with 14 steps 1: 63 percent 3: 6 n HCl 4: 96 percent / liquid HF 5: 98 percent / HBr, HOAc / Ambient temperature 6: 75 percent / H₂ / Pd/C / H₂O; methanol 7: SOCl₂ 8: 85 percent / H₂ / Pd / toluene 9: 82 percent / Pb(OAc)2 / tetrahydrofuran 10: NaH / dioxane 11: NaH / dimethylformamide 12: various solvent(s) / 1 h / 50 °C 13: 44 percent / NaH, O₂ / tetrahydrofuran; dimethylformamide
	Multi-step reaction with 13 steps 1: 63 percent 3: 6 n HCl 4: 96 percent / liquid HF 5: 98 percent / HBr, HOAc / Ambient temperature 6: 75 percent / H₂ / Pd/C / H₂O; methanol 7: SOCl₂ 8: 85 percent / H₂ / Pd / toluene 9: 82 percent / Pb(OAc)2 / tetrahydrofuran 10: NaH / dioxane 11: NaH / dimethylformamide 12: 44 percent / NaH, O₂ / tetrahydrofuran; dimethylformamide

Reference： [1]Kirchlechner; Rogalski [Tetrahedron Letters, 1980, vol. 21, # 3, p. 247 - 250]
[2]Kirchlechner; Rogalski [Tetrahedron Letters, 1980, vol. 21, # 3, p. 247 - 250]
[3]Kirchlechner; Rogalski [Tetrahedron Letters, 1980, vol. 21, # 3, p. 247 - 250]

24
[ 2401-24-3 ]
(5aR,6aS,7R)-1,8,11-Trihydroxy-10,12-dioxo-7-thiobenzoylamino-6,6a,7,10,10a,12-hexahydro-5aH-5-thia-naphthacene-9-carboxylic acid amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 12 steps 1: 63 percent 3: 6 n HCl 4: 96 percent / liquid HF 5: 98 percent / HBr, HOAc / Ambient temperature 6: 75 percent / H₂ / Pd/C / H₂O; methanol 7: SOCl₂ 8: 85 percent / H₂ / Pd / toluene 9: 82 percent / Pb(OAc)2 / tetrahydrofuran 10: NaH / dioxane 11: NaH / dimethylformamide 12: various solvent(s) / 1 h / 50 °C
	Multi-step reaction with 12 steps 1: 63 percent 3: 6 n HCl 4: 96 percent / liquid HF 5: 98 percent / HBr, HOAc / Ambient temperature 6: 75 percent / H₂ / Pd/C / H₂O; methanol 7: SOCl₂ 8: 85 percent / H₂ / Pd / toluene 9: 82 percent / Pb(OAc)2 / tetrahydrofuran 10: NaH / dioxane 11: NaH / dimethylformamide 12: various solvent(s) / 1 h / 50 °C
	Multi-step reaction with 11 steps 1: 63 percent 3: 6 n HCl 4: 96 percent / liquid HF 5: 98 percent / HBr, HOAc / Ambient temperature 6: 75 percent / H₂ / Pd/C / H₂O; methanol 7: SOCl₂ 8: 85 percent / H₂ / Pd / toluene 9: 82 percent / Pb(OAc)2 / tetrahydrofuran 10: NaH / dioxane 11: NaH / dimethylformamide

Reference： [1]Kirchlechner; Rogalski [Tetrahedron Letters, 1980, vol. 21, # 3, p. 247 - 250]
[2]Kirchlechner; Rogalski [Tetrahedron Letters, 1980, vol. 21, # 3, p. 247 - 250]
[3]Kirchlechner; Rogalski [Tetrahedron Letters, 1980, vol. 21, # 3, p. 247 - 250]

25
[ 2401-24-3 ]
[ 5188-07-8 ]
[ 473255-65-1 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium nitrite In water at 0 - 50℃; for 19.25h;	25 Preparation 25; 4-CHLORO-3- (METHYLSULFANYL PHENOL; A solution of 2-chloro-5-methoxyaniline (5. 0g, 32MMOL) in 2N hydrochloric acid (60ML) was heated at 50°C for 30min then cooled to 0°C. A solution of sodium nitrite (2. 41 G, 35MMOL) in water (30ml) was added dropwise and the mixture was stirred at 0°C for 45min then added slowly to a solution of sodium methane thiolate (4.45g, 63MMOL) in water (120ML). The mixture was allowed to warm to room temperature and stirred for 18h, then extracted with diethyl diethyl ether (2X250ML). The organic phase was washed with 2N sodium hydroxide solution, dried over MGS04 and the solvent removed under reduced pressure. The residue was purified by flash column chromatography using ethyl acetate: cyclohexane (5: 95 to 10: 90) as eluant to give 1- chloro-4-methoxy-2- (methylsulfanyl) benzene (2.88g) as a brown oil. Boron tribromide (1 M in dichloromethane, 31 ML, 31 MMOL) was added dropwise to a solution of 1-chloro-4-methoxy-2- (methylsulfanyl) benzene (2.88g, 15MMOL) in DICHLOROMETHANE (80ml) at 0°C. The mixture was allowed to warm to room temperature, stirred for 72h then cooled to 0°C. A solution of DIETHANOLAMINE (10MOL) in DICHLOROMETHANE (20ML) was added dropwise (Caution-strong exotherm.) and the mixture was stirred at ambient temperature for 15 min once addition was complete, then partitioned between dichloromethane and 2N hydrochloric acid. The organic phase was washed with water, dried over MGS04 and the solvent removed under reduced pressure. The residue was purified by flash column chromatography using ethyl acetate: cyclohexane (10: 90 to 85: 15) as eluant to give 4-chloro-3- (methylsulfanyl) phenol (2.12g) as a brown oil. 'H NMR (400MHZ, CDCl3) : A = 7.10-7. 18 (1H, d), 6.62 (1H, s), 6.48-6. 54 (1H, d), 4.97 (1 H, s), 2.42 (3H, s) ppm. LRMS (electrospray) : M/Z [M-H] + 173

Reference： [1]Current Patent Assignee: PFIZER INC - WO2005/9966, 2005, A1 Location in patent: Page/Page column 69-70

26
[ 10198-68-2 ]
[ 2401-24-3 ]
[ 438248-48-7 ]

Yield	Reaction Conditions	Operation in experiment
55%		113 4-(2-Chloro-5-methoxyanilino)-2,6-di(2-pyridinyl)pyrimidine EXAMPLE 113 4-(2-Chloro-5-methoxyanilino)-2,6-di(2-pyridinyl)pyrimidine The title compound was prepared from a mixture of 4-chloro-2,6-di(2-pyridinyl)pyrimidine (25 mg, 0.093 mmol) and 2-chloro-5-methoxyaniline (27 mg, 0.140 mmol) similar to Example 111 and isolated as a white solid (20 mg, 55%). 1H NMR (CDCl3): 8.87-8.82 (m, 1H), 8.72-8.64 (m, 3H), 8.08 (d, J=2.7 Hz, 1H), 7.92 (s, 1H), 7.90-7.86 (m, 2H), 7.45-7.38 (m, 3H), 7.33 (d, J=8.7 Hz, 1H), 6.67 (dd, J=3.0, 9.0 Hz, 1H), 3.91 (s, 3H).

Reference： [1]Current Patent Assignee: IMMUNE PHARMACEUTICALS INC - US2003/69239, 2003, A1

27
[ 2401-24-3 ]
[ 77168-31-1 ]
[ 438247-87-1 ]

Yield	Reaction Conditions	Operation in experiment
44%		52 4-(2-Chloro-5-methoxyanilino)-6-methyl-2-(2-pyridinyl)pyrimidine EXAMPLE 52 4-(2-Chloro-5-methoxyanilino)-6-methyl-2-(2-pyridinyl)pyrimidine The title compound was prepared from a mixture of 4-chloro-6-methyl-2-(2-pyridinyl)pyrimidine (50 mg, 0.243 mmol) and 2-chloro-5-methoxyaniline (47 mg, 0.243 mmol) similar to Example 13 and isolated as a tan oil (35 mg, 44%). 1H NMR (CDCl3): 8.82-8.80 (m, 1H), 8.47 (d, J=7.8 Hz, 1H), 7.86-7.81 (m, 1H), 7.77 (d, J=2.7 Hz, 1H), 7.41-7.36 (m, 1H), 7.36 (s, 1H), 7.30 (s, 1H), 6.68 (s, 1H), 6.65 (dd, J=2.7, 8.7 Hz, 1H), 3.85 (s, 3H), 2.55 (s, 3H).

Reference： [1]Current Patent Assignee: IMMUNE PHARMACEUTICALS INC - US2003/69239, 2003, A1

28
[ 2401-24-3 ]
[ 473255-65-1 ]

Yield	Reaction Conditions	Operation in experiment
80%	With sodium nitrite; sodium thiomethoxide In hydrogenchloride; water	17.i (i) (i) Preparation of 1-chloro-4-methoxy-2-(methylsulfanyl)benzene 2-Chloro-5-methoxyaniline (13.83 g, 87.8 mmol) (prepared according to H. F. Faith, M. F. Bahler, H. J. Florestano, J. Am. Chem. Soc., 1955, 77, 543) was dissolved in 2M HCl (160 mL) by heating to 50° C. and then cooled to 0° C. with stirring to produce a fine precipitate. A solution of NaNO2 (6.66 g, 96.5 mmol) in water (60 mL) was then added dropwise and the mixture was stirred at 0° C. for 1 h. The reaction mixture was then transferred to a pressure equalized dropping funnel containing ice and added dropwise to a solution of NaSMe (12.3 g, 175 mmol) in water (352 mL) [Caution, this reaction can generate potentially explosive methylsulfanyldiazenes]. Mixture stirred overnight, then extracted with ether (2*500 mL) and the combined organic extracts were dried (MgSO4) and evaporated. The residue was partitioned between ether (750 mL) and 2M NaOH (750 mL) and the organic phase was dried (MgSO4) and evaporated to give crude thioether (~80% pure) (13.22 g, 80%) as a brown oil which was used without further purification; δH (CDCl3, 400 MHz) 2.41 (3H, s), 3.75 (3H, s), 6.58 (1H, dd), 6.67 (1H, d), 7.20 (1H, d).

Reference： [1]Current Patent Assignee: PFIZER INC - US2003/207857, 2003, A1

29
[ 204394-70-7 ]
[ 2401-24-3 ]
[ 438247-89-3 ]

Yield	Reaction Conditions	Operation in experiment
25%		54 4-(2-Chloro-5-methoxyanilino)-2-(4-pyridinyl)-6-(trifluoromethyl)pyrimidine EXAMPLE 54 4-(2-Chloro-5-methoxyanilino)-2-(4-pyridinyl)-6-(trifluoromethyl)pyrimidine The title compound was prepared from a mixture of 4-chloro-2-(4-pyridinyl)-6-(trifluoromethyl)pyrimidine (50 mg, 0.193 mmol) and 2-chloro-5-methoxyaniline (38 mg, 0.193 mmol) similar to Example 13 and isolated as a pink solid (18 mg, 25%). 1H NMR (CDCl3): 8.82 (dd, J=1.4, 4.7 Hz, 2H), 8.32 (dd, J=1.7, 4.4 Hz, 2H), 7.84 (d, J=2.1 Hz, 1H), 7.50 (s, 1H), 7.41 (d, J=8.7 Hz, 1H), 7.02 (s, 1H), 6.77 (dd, J=3.3, 9.3 Hz, 1H), 3.90 (s, 3H).
	With hydrogenchloride In water

Reference： [1]Current Patent Assignee: IMMUNE PHARMACEUTICALS INC - US2003/69239, 2003, A1
[2]Location in patent: scheme or table Sirisoma, Nilantha; Pervin, Azra; Nguyen, Bao; Crogan-Grundy, Candace; Kasibhatla, Shailaja; Tseng, Ben; Drewe, John; Cai, Sui Xiong [Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 8, p. 2305 - 2309]

30
[ 263897-42-3 ]
[ 2401-24-3 ]
[ 438247-83-7 ]

Yield	Reaction Conditions	Operation in experiment
45%		48 4-(2-Chloro-5-methoxyanilino)-6-(methoxymethyl)-2-(2-methyl-1,3-thiazol-4-yl)pyrimidine EXAMPLE 48 4-(2-Chloro-5-methoxyanilino)-6-(methoxymethyl)-2-(2-methyl-1,3-thiazol-4-yl)pyrimidine The title compound was prepared from a mixture of 4-chloro-6-(methoxymethyl)-2-(2-methyl-1,3-thiazol-4-yl)pyrimidine (50 mg, 0.196 mmol) and 2-chloro-5-methoxyaniline (38 mg, 0.196 mmol) similar to Example 13 and isolated as a white solid (33 mg, 45%). 1H NMR (CDCl3): 8.14 (s, 1H), 7.93 (d, J=3.0 Hz, 1H), 7.32 (d, J=8.7 Hz, 1H), 7.22 (s, 1H), 6.86 (s, 1H), 6.64 (dd, J=3.0, 9.3 Hz, 1H), 4.60 (s, 2H), 3.88 (s, 3H), 3.52 (s, 3H), 2.84 (s, 3H).

Reference： [1]Current Patent Assignee: IMMUNE PHARMACEUTICALS INC - US2003/69239, 2003, A1

31
[ 118121-82-7 ]
[ 2401-24-3 ]
[ 438248-67-0 ]

Yield	Reaction Conditions	Operation in experiment
31%		131 4-(6-Chloro-3-methoxyanilino)-2-morpholino-6-(methyl)pyrimidine EXAMPLE 131 4-(6-Chloro-3-methoxyanilino)-2-morpholino-6-(methyl)pyrimidine The title compound was prepared from a mixture of 4-(4-chloro-6-methyl-pyrimidin-2-yl)-morpholine (23 mg, 0.108 mmol) and 6-chloro-m-anisidine (31 mg, 0.161 mmol) similar to Example 117 and isolated as a white solid (11 mg, 31%). 1H NMR (CDCl3): 8.27 (d, J=3.0 Hz, 1H), 7.91 (s, 1H), 7.27 (d, J=9.0 Hz, 1H), 6.97 (s, 1H), 6.54 (dd, J=3.0, 8.7 Hz, 1H), 3.80 (s, 3H), 3.77 (s, 8H), 2.14 (s, 3H).
	With hydrogenchloride In water

Reference： [1]Current Patent Assignee: IMMUNE PHARMACEUTICALS INC - US2003/69239, 2003, A1
[2]Location in patent: scheme or table Sirisoma, Nilantha; Pervin, Azra; Nguyen, Bao; Crogan-Grundy, Candace; Kasibhatla, Shailaja; Tseng, Ben; Drewe, John; Cai, Sui Xiong [Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 8, p. 2305 - 2309]

32
diphenyliodonium-2-carboxylate, monohydrate [ No CAS ]
[ 2401-24-3 ]
2-(2-chloro-5-methoxyphenylamino)benzoicacid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In isopropyl alcohol	5.A 2-(2-chloro-5-methoxyanilino)benzoic Acid Example 5A 2-(2-chloro-5-methoxyanilino)benzoic Acid A mixture of 2-chloro-5-methoxyaniline (260 mg, 1.65 mmol), diphenyliodonium-2-carboxylate monohydrate (684 mg, 2.0 mmol), and copper(II) acetate (15 mg, 0.83 mmol) in 2-propanol (4 mL) was heated to reflux for 1.5 hours, diluted with 1N NaOH (10 mL), and extracted with hexanes. The aqueous phase was adjusted to pH <7 with 1M HCl and extracted with ethyl acetate. The combined extracts were washed with brine, dried (MgSO4), filtered, and concentrated to provide the desired product.

Reference： [1]Current Patent Assignee: ABBOTT LABORATORIES INC - US2002/35137, 2002, A1

33
[ 2401-24-3 ]
[ 460346-03-6 ]

Yield	Reaction Conditions	Operation in experiment
2.06 g (40%)	With sodium hydrogencarbonate; acetic acid In dichloromethane; water	59 Preparation of (2-Chloro-5-methoxy-phenyl)-urea (Intermediate 5) Preparation of (2-Chloro-5-methoxy-phenyl)-urea (Intermediate 5) A solution of 2-chloro-5-methoxyaniline (5 g, 25.76 mmol) and potassium cyanate (5.22 g, 64.41 mmol) in a mixture of acetic acid (125 mL) and water (12.5 mL) was stirred at room temperature overnight. The solvent was evaporated, and the residue taken into a mixture of CH2Cl2 and an aqueous saturated solution of NaHCO3. The layers were separated, the aqueous one being extracted three times with CH2Cl2. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated. The crude material was purified by flash chromatography on silica gel (cyclohexane/EtOAc/MeOH: 80/20/2) to give 2.06 g (40%) of intermediate 5. 1H NMR [(CD3)2SO] δ7.97 (br s, 1H, NH), 7.85 (d, J=3.0 Hz, 1H), 7.27 (d, J=9.0 Hz, 1H), 6.54 (dd, J=9.0, 3.0 Hz, 1H), 6.4-(br s, 2H), 3.71 (s, 3H).

Reference： [1]Current Patent Assignee: PFIZER INC - US2002/198198, 2002, A1

34
[ 2401-24-3 ]
[ 2667-20-1 ]
4-chloro-3-methylmercaptoanisole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium hydroxide; sodium hydrogencarbonate; triethylamine; sodium nitrite In water; toluene	5.a α-[3-(2'-chloro-4'-trifluoromethylphenoxy)-6-chlorothio] propionic acid methyl ester (a) With efficient stirring, 241 g of 2-chloro-5-methoxyaniline are added to 310 ml of water and 385 ml of conc. hydrochloric acid, followed by the addition of 750 g of ice. The mixture is cooled to -10° C. and a solution of 111 g of sodium nitrite in 150 ml of water are added all at once, whereupon the temperature rises to 10° C. After 30 minutes excess nitrite is destroyed with sulphamic acid and the solution is clarified by filtration. This diazo solution is added dropwise at 55°-60° C. to a solution of 300 ml of water, 800 ml of toluene, 225 g of potassium methylxanthogenate, 85 g of sodium bicarbonate and 75 ml of 30% sodium hydroxide solution. When the very vigorous evolution of gas has ceased the organic phase is separated, washed with water, dried over sodium sulphate and added dropwise to 100 ml of triethylamine at 70° C. After refluxing for 2 hours, cooling, and adding 200 ml of 30% sodium hydroxide solution, the organic phase is separated and distilled, affording 160 g of 4-chloro-3-methylmercaptoanisole with a boiling point of 138°-145° C./11 mbar.

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - US4349377, 1982, A

35
[ 2401-24-3 ]
[ 140-89-6 ]
[ 59429-73-1 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; potassium hydroxide; sodium nitrite In ethanol; water	1.a EXAMPLE 1 a. A mixture of 450 ml of concentrated hydrochloric acid and 1,200 ml of water is added to 157.6 g of 2-chloro-5-methoxy-aniline, while stirring, and the mixture is diazotised with a solution of 69 g of NaNO2 in 130 ml of water at 0°-5°. The mixture is then buffered with sodium acetate and the diazonium salt solution is added dropwise, while stirring, to a solution, at 70°, of 256 g of potassium ethylxanthate in 360 ml of water. After cooling, the mixture is worked up with CH2 Cl2 and the resulting crude xanthic acid ester is saponified with KOH in ethanol and the mixture is evaporated, acidified and distilled with steam to give 2-chloro-5-methoxy-thiophenol; b.p. 110°/0.5 mm.

Reference： [1]Current Patent Assignee: MERCK KGAA - US4024272, 1977, A

36
[ 1072-85-1 ]
[ 2401-24-3 ]
[ 1041143-72-9 ]

Yield	Reaction Conditions	Operation in experiment
85%	With sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate In toluene for 18h; Heating;

Reference： [1]Bedford, Robin B.; Betham, Michael; Charmant, Jonathan P.H.; Weeks, Amanda L. [Tetrahedron, 2008, vol. 64, # 26, p. 6038 - 6050]

37
2-phenylpropionyl chloride [ No CAS ]
[ 2401-24-3 ]
[ 1188327-96-9 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In dichloromethane at 0 - 25℃;

Reference： [1]Ackermann, Lutz; Vicente, Ruben; Hofmann, Nora [Organic Letters, 2009, vol. 11, # 19, p. 4274 - 4276]

38
[ 576-83-0 ]
[ 2401-24-3 ]
[ 1188930-01-9 ]

Yield	Reaction Conditions	Operation in experiment
99%	With palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene for 18h; Inert atmosphere; Reflux;

Reference： [1]Bedford, Robin B.; Butts, Craig P.; Haddow, Mairi F.; Osborne, Robert; Sankey, Rosalind F. [Chemical Communications, 2009, # 32, p. 4832 - 4834]

39
[ 2401-24-3 ]
[ 121221-93-0 ]
[ 1192159-88-8 ]

Yield	Reaction Conditions	Operation in experiment
60%	With copper(l) iodide; potassium <i>tert</i>-butylate In toluene at 105℃; for 2h; Inert atmosphere;

Reference： [1]Ackermann, Lutz; Barfuesser, Sebastian; Potukuchi, Harish K. [Advanced Synthesis and Catalysis, 2009, vol. 351, # 7-8, p. 1064 - 1072]

40
[ 1228378-20-8 ]
[ 1228378-54-8 ]
[ 2401-24-3 ]
[ 83490-71-5 ]

Yield	Reaction Conditions	Operation in experiment
1: 14% 2: 48% 3: 52%	With phosphate potassium salt; oxygen; copper diacetate In N,N-dimethyl-formamide at 80℃; for 10h;

Reference： [1]Chiba, Shunsuke; Zhang, Line; Lee, Jian-Yuan [Journal of the American Chemical Society, 2010, vol. 132, # 21, p. 7266 - 7267]

41
[ 2401-24-3 ]
[ 1488-42-2 ]
2-(2-chloro-5-methoxyphenylamino)benzoicacid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	With copper diacetate In N,N-dimethyl-formamide at 90℃; for 15h;

Reference： [1]Location in patent: experimental part Putic, Aleksandar; Stecher, Lambert; Prinz, Helge; Mueller, Klaus [European Journal of Medicinal Chemistry, 2010, vol. 45, # 8, p. 3299 - 3310]

42
[ 2401-24-3 ]
[ 106-51-4 ]
2-(2-chloro-5-methoxyphenyl)-1,4-benzoquinone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	Stage #1: 2-chloro-5-methoxyaniline With hydrogenchloride; sodium nitrite In water at 0 - 5℃; for 1.5h; Stage #2: p-benzoquinone With sodium acetate In water

Reference： [1]Location in patent: experimental part Termentzi, Aikaterini; Khouri, Inana; Gaslonde, Thomas; Prado, Soizic; Saint-Joanis, Brigitte; Bardou, Fabienne; Amanatiadou, Elsa P.; Vizirianakis, Ioannis S.; Kordulakova, Jana; Jackson, Mary; Brosch, Roland; Janin, Yves L.; Daffé, Mamadou; Tillequin, Franois; Michel, Sylvie [European Journal of Medicinal Chemistry, 2010, vol. 45, # 12, p. 5833 - 5847]

43
2-bromo-1,3-dimethyl-1H-indole [ No CAS ]
[ 2401-24-3 ]
[ 1290628-97-5 ]

Yield	Reaction Conditions	Operation in experiment
37%	With palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene for 18h; Reflux; Inert atmosphere;

Reference： [1]Bedford, Robin B.; Fey, Natalie; Haddow, Mairi F.; Sankey, Rosalind F. [Chemical Communications, 2011, vol. 47, # 12, p. 3649 - 3651]

44
[ 2401-24-3 ]
[ 882-33-7 ]
[ 1303613-74-2 ]

Yield	Reaction Conditions	Operation in experiment
83%	With iron(III) trifluoride; iodine In acetonitrile at 80℃; for 36h; Inert atmosphere; regioselective reaction;

Reference： [1]Location in patent: experimental part Fang, Xiao-Li; Tang, Ri-Yuan; Zhang, Xing-Guo; Li, Jin-Heng [Synthesis, 2011, # 7, p. 1099 - 1105]

45
[ 2401-24-3 ]
[ 145742-50-3 ]

Reference： [1]Patent: US2012/46469,2012,A1

46
[ 2401-24-3 ]
4-bromo-2-chloro-5-methoxyphenylamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione In ethyl acetate at -5℃; for 1.33333h;	A ExampleStep A: Preparation of 4-Bromo-2-chloro-5-methoxyaniline1,3-Dibromo-5,5-dimethylhydantoin (commercially available, for example, from Aldrich) (9.1 g, 32 mmol) was added over 20 minutes to a stirred solution of 6-chloro-3-methoxyaniline (commercially available, for example, from Apollo Scientific) (10.0 g, 63 mmol) in ethyl acetate (150 ml) at -5° C. The resulting solution was stirred at -5° C. for 1 hour then washed with a solution of potassium carbonate (6 g, 43 mmol) in water (40 ml and then with water (20 ml). The resulting solution was concentrated under reduced pressure to give 4-bromo-2-chloro-5-methoxyaniline as a pale brown solid (14.3 g, 95%).1H NMR (400 MHz, CDCl3) δH (ppm) 7.38 (1H, s), 6.34 (1H, s), 4.02-4.14 (2H, br s), 3.83 (3H, s)m/z (ES+) 236 (M+H)
1.96 g	With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione In ethyl acetate for 1h; Cooling with ice; Inert atmosphere;	1 6-Chloro-3-methoxyaniline (1.57 g, 10 mmol) was dissolved in ethyl acetate (15 mL)Under ice-cooling,To the above solution was added portionwise1,3-dibromo-5,5-Dimethylhydantoin(3.1 g, ll mmol),After the addition, the reaction solution was allowed to react under ice-cooling for 1 hour,The reaction solution was quenched with saturated potassium carbonate solution,The organic phase was separated,Respectively, with water,Washed with a saturated saline solution,Dried over anhydrous sodium sulfate,Filtered, concentrated under reduced pressure,Bromo-2-chloro-5-methoxyaniline(Brown solid, 1.96 g).

Reference： [1]Current Patent Assignee: THERAVANCE BIOPHARMA, INC. - US2012/46469, 2012, A1 Location in patent: Page/Page column 3
[2]Current Patent Assignee: SHANGHAI PHARMACEUTICALS HOLDING COMPANY LIMITED - CN103848785, 2016, B Location in patent: Paragraph 0189; 0190

47
[ 36854-57-6 ]
[ 2401-24-3 ]
C₁₇H₁₈ClNO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-chloro-5-methoxyaniline With triethylamine In dichloromethane at 20℃; for 0.0833333h; Inert atmosphere; Stage #2: 2-Phenylbutyryl chloride In dichloromethane for 17h; Inert atmosphere;

Reference： [1]Beyer, Astrid; Buendia, Julien; Bolm, Carsten [Organic Letters, 2012, vol. 14, # 15, p. 3948 - 3951]

48
[ 2401-24-3 ]
[ 707-07-3 ]
[ 1402939-03-0 ]

Yield	Reaction Conditions	Operation in experiment
59%	With toluene-4-sulfonic acid In toluene for 3h; Inert atmosphere; Reflux;

Reference： [1]Sadig, Jessie E. R.; Foster, Radleigh; Willis, Michael C.; Wakenhut, Florian [Journal of Organic Chemistry, 2012, vol. 77, # 21, p. 9473 - 9486,14]

49
[ 2401-24-3 ]
[ 98-88-4 ]
N-(2-chloro-5-methoxyphenyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With triethylamine In tetrahydrofuran at 0℃; for 3h; Inert atmosphere;

Reference： [1]Sadig, Jessie E. R.; Foster, Radleigh; Willis, Michael C.; Wakenhut, Florian [Journal of Organic Chemistry, 2012, vol. 77, # 21, p. 9473 - 9486,14]

50
[ 2401-24-3 ]
[ 123-73-9 ]
8-chloro-2-methyl-5-(methyloxy)-quinoline hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With hydrogenchloride; chloranil In water; butan-1-ol for 0.75h; Reflux; Inert atmosphere;
	With hydrogenchloride; chloranil In water; butan-1-ol

Reference： [1]Armitage, Mark; Bret, Guillaume; Choudary, Bernie M.; Kingswood, Mike; Loft, Mike; Moore, Steve; Smith, Steve; Urquhart, Michael W. J. [Organic Process Research and Development, 2012, vol. 16, # 10, p. 1626 - 1634]
[2]Current Patent Assignee: FORMA THERAPEUTICS, INC. - WO2021/3163, 2021, A1 Location in patent: Paragraph 0113

51
[ 2401-24-3 ]
[ 1426155-90-9 ]

Yield	Reaction Conditions	Operation in experiment
1.81 g	Stage #1: 2-chloro-5-methoxyaniline With tetrafluoroboric acid; sodium nitrite In water at 0℃; for 0.5h; Stage #2: With copper(I) bromide; phosphorus trichloride In ethyl acetate at 20 - 50℃;

Reference： [1]Crisalli, Pete; Kool, Eric T. [Organic Letters, 2013, vol. 15, # 7, p. 1646 - 1649]

52
[ 2401-24-3 ]
[ 2039-88-5 ]
[ 92483-74-4 ]

Yield	Reaction Conditions	Operation in experiment
53%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; sodium t-butanolate; DavePhos In 1,4-dioxane at 115℃; for 6h; Inert atmosphere;	9 4.6 General procedure for palladium-catalyzed synthesis of dibenzazepine derivatives 35-41 (GP-5) General procedure: A mixture of 2-bromostyrene (549mg, 3.00mmol), the appropriate 2-chloroaniline derivative (3.00mmol), Pd(dba)3 (68mg, 0.075mmol), DavePhos (79mg, 0.20mmol), and NaOtBu (864mg, 9.00mmol) in dry 1,4-dioxane (10mL) was stirred under a N2 atmosphere at 115°C for 6h. After it had been cooled down to rt, EtOAc (150mL) was added. The mixture was washed with water (5×150mL) and subsequently with brine (150mL). The organic phase was separated and dried over MgSO4. After evaporation of the solvent, the residue was submitted to column chromatography (SiO2, eluent: petroleum ether/EtOAc 20:1). The yellow fraction was collected, and evaporation of the eluent in vacuo gave the desired product.

Reference： [1]Tian, Maoqun; Abdelrahman, Aliaa; Weinhausen, Stephanie; Hinz, Sonja; Weyer, Stefanie; Dosa, Stefan; El-Tayeb, Ali; Müller, Christa E. [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 3, p. 1077 - 1088]

53
[ 2401-24-3 ]
[ 56-81-5 ]
[ 16026-85-0 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-chloro-5-methoxyaniline; glycerol Stage #2: With hydrogen bromide In water	158 61. The Suzuki reaction was carried out using the conditions of Example 10. Coupling partner 8-chloro-5-(furo[3,2-c]pyrid in-4-yloxy)quinoline was synthesized in the following manner: Skrau preaction of 2-chloro-5-methoxyaniline with propane-i ,2,3-triol afforded 8-chloro-5-methoxyquinoline, which was demethylated with aqueous hydrobromic acid. The resulting 8-chloroquinolin-5-ol was then reacted with 4-chlorofuro[3,2-c]pyridine using cesium carbonate indimethyl sulfoxide.

Reference： [1]Current Patent Assignee: PFIZER INC - WO2014/72881, 2014, A1 Location in patent: Page/Page column 151; 164

54
[ 2401-24-3 ]
[ 375368-83-5 ]
3-fluoro-7-methoxy-1-methyl-9H-pyrido[3,4-b]indole [ No CAS ]

Reference： [1]Patent: US2014/288068,2014,A1

55
[ 2401-24-3 ]
[ 126717-59-7 ]
3,7-dimethoxy-1-methyl-9H-pyrido[3,4-b]indole [ No CAS ]

Reference： [1]Patent: US2014/288068,2014,A1

56
[ 2401-24-3 ]
[ 375368-83-5 ]
N-(2-chloro-5-methoxyphenyl)-6-fluoro-2-methylpyridin-3-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With 2-(dicyclohexylphosphino)-2',4',6'-tri-1-propyl-1,1'-biphenyl; palladium diacetate; caesium carbonate; at 100℃; for 15h;Microwave irradiation; Inert atmosphere;	<strong>[375368-83-5]3-bromo-6-fluoro-2-methylpyridine</strong> (Matrix catalog No.024607, 0.230 g, 1.209 mmol), 2-(dicyclohexylphosphino)-2',4',6'-tri-1-propyl-1,1'-biphenyl (0.043 g, 0.091 mmol), cesium carbonate (0.473 g, 1.450 mmol) and palladium (II) acetate (0.014 g, 0.060 mmol) were added to a microwave vial. Then, 2-chloro-5-methoxyaniline (0.2 g, 1.269 mmol) was added. The solvent was degassed with argon twice. The reaction was heated on a heating block to 100 C. for 15 hours. The crude reaction mixture was cooled to room temperature and then filtered through celite. The celite was rinsed repeatedly with ethyl acetate to collect the crude product mixture. A reverse-phase column was run (water, acetonitrile) to give N-(2-chloro-5-methoxyphenyl)-6-fluoro-2-methylpyridin-3-amine (0.246 g, 76% yield). 1H NMR (CDCl3, 400 MHz) delta 7.65 (t, 1H, J=8.4 Hz), 7.24 (s, 1H), 6.79 (dd, 1H, J=3.6, 8.4 Hz), 6.35 (dd, 1H, J=2.8, 8.8 Hz), 6.15 (d, 1H, J=2.8 Hz), 5.71 (s, 1H), 3.69 (s, 3H), 2.44 (s, 3H).

Reference： [1]Patent: US2014/288068,2014,A1 .Location in patent: Paragraph 0501-0502

57
[ 2401-24-3 ]
[ 126717-59-7 ]
N-(2-chloro-5-methoxyphenyl)-6-methoxy-2-methylpyridin-3-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With palladium diacetate; caesium carbonate; XPhos; at 100℃; for 15h;Microwave irradiation; Inert atmosphere;	<strong>[126717-59-7]3-bromo-6-methoxy-2-methylpyridine</strong> (Aldrich catalog No.758191-1G,0.3 g, 1.485 mmol), 2-(dicyclohexylphosphino)-2',4',6'-tri-i-propyl-1,1'-biphenyl (0.053 g, 0.111 mmol), cesium carbonate (0.581 g, 1.782 mmol) and palladium (II) acetate (0.017 g, 0.074 mmol) were added to a microwave vial. Then, 2-chloro-5-methoxyaniline (Chemimpex catalog No.27675, 0.246 g, 1.559 mmol) was added. The solvent was degassed with argon twice. The reaction was heated on a heating block to 100 C. for 15 hours. The crude reaction mixture was cooled to room temperature and then filtered through celite. The celite was rinsed repeatedly with ethyl acetate to collect the crude product mixture. A reverse-phase column was run (water, acetonitrile) to give N-(2-chloro-5-methoxyphenyl)-6-methoxy-2-methylpyridin-3-amine (0.286 g, 69% yield). 1H NMR (CDCl3, 400 MHz) delta 7.42 (d, 1H, J=8.4 Hz), 7.20 (d, 1H, J=8.4 Hz), 6.60 (d, 1H, J=8.4 Hz), 6.26 (dd, 1H, J=2.8, 8.8 Hz), 6.00 (d, 1H, J=2.8 Hz), 5.65 (s, 1H), 3.93 (s, 3H), 3.66 (s, 3H), 2.37 (s, 3H).

Reference： [1]Patent: US2014/288068,2014,A1 .Location in patent: Paragraph 0507-0508

58
[ 2401-24-3 ]
[ 10168-00-0 ]
N-(2-chloro-5-methoxyphenyl)-3-methylpyridin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With 2-(dicyclohexylphosphino)-2',4',6'-tri-1-propyl-1,1'-biphenyl; palladium diacetate; caesium carbonate In toluene at 100℃; for 16h; Microwave irradiation; Inert atmosphere;	41 Example 41 Synthesis of 7-methoxy-4-methyl-5H-pyrido[4,3-b]indole 4-Bromo-3-methylpyridine (Astatech catalog No.56516, 0.3 g, 1.744 mmol), 2-(dicyclohexylphosphino)-2',4',6'-tri-1-propyl-1,1'-biphenyl (0.062 g, 0.131 mmol), cesium carbonate (0.682 g, 2.093 mmol), anhydrous toluene (5 mL) and palladium (II) acetate (0.020 g, 0.087 mmol) were added to a microwave vial. Then, 2-chloro-5-methoxyaniline (0.289 g, 1.831 mmol) was added. The vial was purged with argon twice. The reaction was heated to 100° C. for 16 hours. The crude reaction mixture was filtered with celite. The celite was rinsed repeatedly with ethyl acetate to collect the crude product mixture. A normal-phase column was run (ethylacetate/hexanes) to give N-(2-chloro-5-methoxyphenyl)-6-methoxy-2-methylpyridin-3-amine (0.41 g, 95% yield).

Reference： [1]Current Patent Assignee: OSTEOQC - US2014/288068, 2014, A1 Location in patent: Paragraph 0511-0512

59
[ 2401-24-3 ]
[ 126717-60-0 ]
6-(benzyloxy)-N-(2-chloro-5-methoxyphenyl)-2-methylpyridin-3-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With 2-(dicyclohexylphosphino)-2',4',6'-tri-1-propyl-1,1'-biphenyl; palladium diacetate; caesium carbonate; In toluene; at 100℃; for 15.0h;Microwave irradiation; Inert atmosphere;	<strong>[126717-60-0]6-(benzyloxy)-3-bromo-2-methylpyridine</strong> (ArkPharm catalog No.AK-27978, 0.1 g, 0.360 mmol), 2-(dicyclohexylphosphino)-2',4',6'-tri-1-propyl-1,1'-biphenyl (Chemimpex catalog No.27675, 0.013 g, 0.027 mmol), cesium carbonate (0.141 g, 0.431 mmol) and palladium (II) acetate (4.04 mg, 0.018 mmol) were added to a microwave vial containing a stir bar and 5 mL of anhydrous toluene. Then, 2-chloro-5-methoxyaniline (Chemimpex catalog No.27675, 0.059 g, 0.378 mmol) was added. The solvent was degassed with argon twice. The reaction was heated on a heating block to 100 C. for 15 hours. The crude reaction mixture was cooled to room temperature and then filted through celite. The celite was rinsed repeatedly with ethyl acetate to collect the crude product mixture. A normal phase ethylacetate/hexanes column was run on the crude mixture to give 6-(benzyloxy)-N-(2-chloro-5-methoxyphenyl)-2-methylpyridin-3-amine (0.1195 g, 94% yield). 1H NMR (CDCl3, 400 MHz) delta 7.39 (m, 6H), 7.20 (d, 1H, J=8.8 Hz), 6.67 (d, 1H, J=8.4 Hz), 6.26 (dd, 1H, J=2.8, 8.8 Hz), 6.01 (d, 1H, J=2.8 Hz), 5.65 (s, 1H), 5.37 (s, 2H), 3.65 (s, 3H), 2.38 (s, 3H).

Reference： [1]Patent: US2014/288068,2014,A1 .Location in patent: Paragraph 0448-0449

60
[ 2401-24-3 ]
[ 590371-58-7 ]
N-(2-chloro-5-methoxyphenyl)-2-(trifluoromethyl)pyridin-3-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70.2%	With 2-(dicyclohexylphosphino)-2',4',6'-tri-1-propyl-1,1'-biphenyl; palladium diacetate; caesium carbonate; In toluene; at 100℃; for 15h;Microwave irradiation; Inert atmosphere;	<strong>[590371-58-7]3-bromo-2-(trifluoromethyl)pyridine</strong> (0.4 g, 1.770 mmol), 2-(Dicyclohexylphosphino)-2',4',6'-tri-1-propyl-1,1'-biphenyl (0.063 g, 0.133 mmol), Cesium carbonate (0.692 g, 2.124 mmol) and Palladium (II) Acetate (0.020 g, 0.088 mmol) were added to a microwave vial. Then, 2-chloro-5-methoxyaniline (0.293 g, 1.858 mmol) was added. The vial was purged with argon repeatedly. Dry toluene was added. The reaction was heated to 100 C. for 15 hours. The reaction mixture was filtered through celite, concentrated en vacuo. Normal phase chromatography (ethyl acetate/hexanes) was used to purify the crude material to give N-(2-chloro-5-methoxyphenyl)-2-(trifluoromethyl)pyridin-3-amine (0.376 g, 1.242 mmol, 70.2% yield).

Reference： [1]Patent: US2014/288068,2014,A1 .Location in patent: Paragraph 0464-0465

61
[ 359-06-8 ]
[ 2401-24-3 ]
N-(2-chloro-5-methoxyphenyl)-2-fluoroacetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	In dichloromethane
	With triethylamine In dichloromethane Cooling with ice;	4i Example 4(i): N-(2-chloro-5-methoxyphenyl)-2-fluoroacetamide Example 4(i): N-(2-chloro-5-methoxyphenyl)-2-fluoroacetamideA solution of fluoroacetyl chloride (3 g, 31 ,1 mmol) was added dropwise to an ice cold solution of 2-chloro-5-methoxyaniline (5 g, 31 ,7 mmol) and triethylamine (4,5 ml, 32,3 mmol) in dichloromethane (20 ml) and left stirring overnight. Water (50 ml) was added and the biphasic mixture was stirred for 2 minutes and then separated. The aqueous phase was extracted with dichloromethane (20 ml) and the combined organic phases were dried over magnesium sulfate (5 g). After evaporation the crude solid material was used in the next step.

Reference： [1]Morisson-Iveson, Véronique; Wadsworth, Harry; Passmore, Joanna; Ewan, Amanda; Nilsen, Sondre; Thaning, Mikkel; Trigg, William [Tetrahedron Letters, 2014, vol. 55, # 37, p. 5141 - 5143]
[2]Current Patent Assignee: GENERAL ELECTRIC CO - WO2015/40148, 2015, A1 Location in patent: Page/Page column 19

62
[ 4858-85-9 ]
[ 2401-24-3 ]
3-chloro-N-(2-chloro-5-methoxyphenyl)pyrazin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	Stage #1: 2-chloro-5-methoxyaniline With sodium hexamethyldisilazane In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Stage #2: 2,3-dichloropyrazine In tetrahydrofuran at 0 - 20℃; for 2h; Inert atmosphere;

Reference： [1]Freitag, Anne; Prajwal, Prajwal; Shymanets, Aliaksei; Harteneck, Christian; Nürnberg, Bernd; Schächtele, Christoph; Kubbutat, Michael; Totzke, Frank; Laufer, Stefan A. [Journal of Medicinal Chemistry, 2015, vol. 58, # 1, p. 212 - 221]

63
[ 123-73-9 ]
[ 2401-24-3 ]
8-chloro-5-methoxy-2-methylquinoline hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With hydrogenchloride; 2,3,5,6-tetrachlorocyclohexa-2,5-diene-1,4-dione In tetrahydrofuran; water monomer; butan-1-ol for 1.75h; Inert atmosphere; Reflux;
77%	Stage #1: 2-chloro-5-methoxybenzenamine With hydrogenchloride; 2,3,5,6-tetrachlorocyclohexa-2,5-diene-1,4-dione In water monomer; butan-1-ol at 100℃; for 1h; Inert atmosphere; Stage #2: trans-Crotonaldehyde In tetrahydrofuran; water monomer; butan-1-ol at 70 - 100℃; Inert atmosphere;	1 Step 1.8-chloro-5-methoxy-2-methylquinoline hydrochloride Into a 5L 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, 2-chloro-5-methoxyaniline (250 g, 1.59 mol) was dissolved in 1-butanol (1200 mL). Then hydrochloric acid (aq, 36.5%, 526.5 mL) and chloranil (456.5 g, 1.86 mol) were added. The resulting mixture was stirred for 1 h at 100oC under nitrogen atmosphere. Then a solution of (E)-but-2-enal (169 mL, 2.06 mol) in 1-butanol (300 mL) was added dropwise. The resulting solution was stirred for 1 h at 100oC under nitrogen atmosphere. The oil bath was cooled to 70oC and tetrahydrofuran (1500mL) was added. Then the resulting mixture was stirred for 1 h at 70oC. The reaction mixture was cooled to 0oC and the solids were filtered. The solids were washed with tetrahydrofuran (3L) at 0oC. This afforded the title compound (300g, 77%) as a yellow solid. MS: (ES, m/z): 208, 210 [M+H]+.
74%	Stage #1: 2-chloro-5-methoxybenzenamine With hydrogenchloride; 2,3,5,6-tetrachlorocyclohexa-2,5-diene-1,4-dione In water monomer; butan-1-ol at 100℃; for 1h; Stage #2: trans-Crotonaldehyde In water monomer; butan-1-ol at 100℃; for 2h;	1.1 Step 1. 8-chloro-5-methoxy-2-methylquinoline hydrochloride Step 1. 8-chloro-5-methoxy-2-methylquinoline hydrochloride [0204] A 1000-mL 3-necked round-bottom flask was charged with 2-chloro-5-methoxy aniline (50 g, 317 mmol), -butanol (120 mL), concentrated hydrochloric acid (37%, 90 mL), and chloranil (tetrachloro-l ,4-benzoquinone) (78 g, 317 mmol). The resulting solution stirred for 1 h at 100 °C in an oil bath. A solution of (E)-crotonaldehyde (28.9 mL, 349 mmol) in -butanol (50 mL) was added dropwise over 1 h. The resulting solution stirred for 1 h at 100 °C in an oil bath and was then cooled to 70 °C. Tetrahydrofuran (650 mL) was added, and the reaction mixture stirred for 1 h at 70 °C and was then cooled to 0 °C. The resulting precipitate was held at 0- 5 °C for 1 h. The mixture was filtered, the solids were washed with cold (ca. 0 °C) THF (2 x 350 mL), and then dried in an oven to afford 8-chloro-5-methoxy-2-methylquinoline hydrochloride (83.0 g, 74%) as a yellow solid. MS (ES, m/z): 208 [M+H]+

74%	With hydrogenchloride; nitrogen; 2,3,5,6-tetrachlorocyclohexa-2,5-diene-1,4-dione	1.1.1 Step 1. Step 1. 8-chloro-5-methoxy-2-methylquinoline hydrochloride Into a 5 L 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, 2-chloro-5-methoxyaniline (250 g, 1.59 mol) was dissolved in 1-butanol (1200 mL). Then hydrochloric acid (aq, 36.5%, 526.5 mL) and chloranil (456.5 g, 1.86 mol) were added. The resulting mixture was stirred for 1 h at 100° C. under nitrogen atmosphere. Then a solution of (E)-but-2-enal (169 mL, 2.06 mol) in 1-butanol (300 mL) was added dropwise. The resulting solution was stirred for 1 h at 100° C. under nitrogen atmosphere. The oil bath was cooled to 70° C. and tetrahydrofuran (1500 mL) was added. Then the resulting mixture was stirred for 1 h at 70° C. The reaction mixture was cooled to 0° C. and the solids were filtered. The solids were washed with tetrahydrofuran (3 L) at 0° C. then dried in an oven to afford 8-chloro-5-methoxy-2-methylquinoline hydrochloride (83.0 g, 74%) as a yellow solid. MS (ES, m/z): 208 [M+H]+.
74%	Stage #1: 2-chloro-5-methoxybenzenamine With hydrogenchloride; 2,3,5,6-tetrachlorocyclohexa-2,5-diene-1,4-dione In water monomer; butan-1-ol at 100℃; for 1h; Inert atmosphere; Stage #2: trans-Crotonaldehyde In butan-1-ol at 100℃; for 1h; Inert atmosphere;	1-1.1 Step 1. 8-chloro-5-methoxy-2-methylquinoline hydrochloride Into a 5 L 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, 2-chloro-5-methoxyaniline (250 g, 1.59 mol) was dissolved in 1-butanol (1200 mL). Then hydrochloric acid (aq, 36.5%, 526.5 mL) and chloranil (456.5 g, 1.86 mol) were added. The resulting mixture was stirred for 1 h at 100° C. under nitrogen atmosphere. Then a solution of (E)-but-2-enal (169 mL, 2.06 mol) in 1-butanol (300 mL) was added dropwise. The resulting solution was stirred for 1 h at 100° C. under nitrogen atmosphere. The oil bath was cooled to 70° C. and tetrahydrofuran (1500 mL) was added. Then the resulting mixture was stirred for 1 h at 70° C. The reaction mixture was cooled to 0° C. and the solids were filtered. The solids were washed with tetrahydrofuran (3 L) at 0° C. then dried in an oven to afford 8-chloro-5-methoxy-2-methylquinoline hydrochloride (83.0 g, 74%) as a yellow solid. MS (ES, m/z): 208 [M+H]+.
74%	Stage #1: 2-chloro-5-methoxybenzenamine With hydrogenchloride; 2,3,5,6-tetrachlorocyclohexa-2,5-diene-1,4-dione In water monomer; butan-1-ol at 100℃; for 1h; Inert atmosphere; Stage #2: trans-Crotonaldehyde In butan-1-ol at 100℃; for 1h; Inert atmosphere;	1-1.1 Step 1. 8-chloro-5-methoxy-2-methylquinoline hydrochloride Into a 5 L 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, 2-chloro-5-methoxyaniline (250 g, 1.59 mol) was dissolved in 1-butanol (1200 mL). Then hydrochloric acid (aq, 36.5%, 526.5 mL) and chloranil (456.5 g, 1.86 mol) were added. The resulting mixture was stirred for 1 h at 100° C. under nitrogen atmosphere. Then a solution of (E)-but-2-enal (169 mL, 2.06 mol) in 1-butanol (300 mL) was added dropwise. The resulting solution was stirred for 1 h at 100° C. under nitrogen atmosphere. The oil bath was cooled to 70° C. and tetrahydrofuran (1500 mL) was added. Then the resulting mixture was stirred for 1 h at 70° C. The reaction mixture was cooled to 0° C. and the solids were filtered. The solids were washed with tetrahydrofuran (3 L) at 0° C. then dried in an oven to afford 8-chloro-5-methoxy-2-methylquinoline hydrochloride (83.0 g, 74%) as a yellow solid. MS (ES, m/z): 208 [M+H]+.

Reference： [1]Chen, Ya; He, Yan-Mei; Zhang, Shanshan; Miao, Tingting; Fan, Qing-Hua [Angewandte Chemie - International Edition, 2019, vol. 58, # 12, p. 3809 - 3813][Angew. Chem., 2019, vol. 131, # 12, p. 3849 - 3853,5]
[2]Current Patent Assignee: FORMA THERAPEUTICS, INC. - WO2019/55877, 2019, A1 Location in patent: Paragraph 0075
[3]Current Patent Assignee: FORMA THERAPEUTICS, INC. - WO2015/74064, 2015, A2 Location in patent: Paragraph 0204
[4]Current Patent Assignee: FORMA THERAPEUTICS, INC. - US2022/88005, 2022, A1
[5]Current Patent Assignee: FORMA THERAPEUTICS, INC. - US2022/88005, 2022, A1 Location in patent: Paragraph 0350; 0351
[6]Current Patent Assignee: FORMA THERAPEUTICS, INC. - US2022/88005, 2022, A1 Location in patent: Paragraph 0350; 0351

64
[ 87-51-4 ]
[ 2401-24-3 ]
N-(2-chloro-5-methoxyphenyl)-2-(1H-indol-3-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 16h; Inert atmosphere;

Reference： [1]Vasudevan; Jachak, Gorakhnath R.; Reddy, D. Srinivasa [European Journal of Organic Chemistry, 2015, vol. 2015, # 34, p. 7433 - 7437]

65
[ 302-17-0 ]
[ 2401-24-3 ]
N-(2-chloro-5-methoxyphenyl)-2-(hydroxyimino)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; hydroxylamine hydrochloride; sodium sulfate In water at 100℃; for 2h;	1.2 N-2-Chioro-5-niethoxyphenyi)-2-(hydroxyimino)acetaniide (3) To a solution of 2-chloro-5-methoxyaniline (2, 27 g, 171 mmol, from Step 1) in 12 M hydrochloric acid (15 mL) and water (600 mL) was added a solution of sodium sulfate (268 g, 1.89 mol) and chloral hydrate (39.7 g, 240 mmol) in water (200 mL). Hydroxylamine hydrochloride (42.9 g, 617 mmol) in water (200 mL) was then added, the resulting solution was stirred at 100 oC for 2 h. After the starting material was consumed, the reaction mixture was cooled to rt, filtered, and washed with water. The resulting solid was dissolved in ethyl acetate (200 mL), the solution was washed with brine (200 mL), the organic phase was dried over anhydrous sodium sulfate, and the solvent was removed under diminished pressure to give the title compound as a yellow solid.

Reference： [1]Current Patent Assignee: SUNNYLIFE PHARMA - WO2016/33228, 2016, A1 Location in patent: Page/Page column 48

66
[ 2401-24-3 ]
[ 98-59-9 ]
N-(2-chloro-5-methoxyphenyl)-4-methylbenzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With pyridine In dichloromethane at 20℃; for 3.5h; Inert atmosphere;

Reference： [1]Yamaguchi, Miyuki; Akiyama, Tomoyo; Sasou, Hirohisa; Katsumata, Haruka; Manabe, Kei [Journal of Organic Chemistry, 2016, vol. 81, # 13, p. 5450 - 5463]

67
[ 2401-24-3 ]
[ 3052-73-1 ]
5-methoxy-N,N-diethylbenzo[d]thiazol-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium <i>tert</i>-butylate In dimethyl sulfoxide at 100℃;	General procedure: In a dried tube, equipped with a magnetic stirrer and a septum, 2-chloroaniline (1.0 mmol) was dissolved in DMSO (3 mL), and t-BuOK(3.0 mmol) was added. The mixture was stirred for 5 min, then dithiocarbamate(1.5 mmol) and tetrakis(triphenylphosphine) palladium(5 mol %) were added. The reaction mixture was heated at 100 °C andthe progress of the reaction was checked by TLC until the starting materialwas consumed. The mixture was cooled to r.t., and the reactionwas quenched with sat. NH4Cl solution (5 mL). The mixture was extractedwith EtOAc, dried over anhydrous Na2SO4 and evaporated undervacuum. The residue was purified by flash column chromatographyto afford the desired product.
91%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium <i>tert</i>-butylate In dimethyl sulfoxide at 100℃;	4.3. Typical procedure for the preparation of 2-aminobenzothiazoles starting from2-chloroanilines in the presence of Pd(PPh3)4 and KOt-Bu (TP3) General procedure: A dried tube, equipped with a magnetic stirred and a septum, 2-chloroaniline (0.13 g,1.0mmol) was dissolved in DMSO (3mL), and KOt-Bu (0.34 g, 3mmol) was added. Themixture was stirred for 5min, and then dithiocarbamate (0.30 g, 1.5mmol) and tetrakispalladium(57.7mg, 5 mmol%) were added. The reaction mixture was then heated at100°C and checked by TLC until the starting material was finished. The reaction wascooled down to room temperature, and then quenched with sat. NH4Cl solution (5mL)and extracted with ethyl acetate, dried over anhydrous Na2SO4 and concentrated undervacuum. The residue was purified by flash column chromatography to afford the desiredproduct (153mg, 86%).

Reference： [1]Xu, Wan; Zeng, Meng-Tian; Liu, Min; Liu, Sha-Sha; Li, Yue-Sheng; Dong, Zhi-Bing [Synthesis, 2017, vol. 49, # 14, p. 3084 - 3090]
[2]Xu, Wan; Zeng, Meng-Tian; Liu, Min; Liu, Xing; Chang, Cai-Zhu; Zhu, Hui; Dong, Zhi-Bing [Journal of Sulfur Chemistry, 2017, vol. 38, # 6, p. 644 - 654]

68
[ 2401-24-3 ]
[ 16906-70-0 ]
5-methoxy-N,N-dimethylbenzo[d]thiazol-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium <i>tert</i>-butylate In dimethyl sulfoxide at 100℃;	General procedure: In a dried tube, equipped with a magnetic stirrer and a septum, 2-chloroaniline (1.0 mmol) was dissolved in DMSO (3 mL), and t-BuOK(3.0 mmol) was added. The mixture was stirred for 5 min, then dithiocarbamate(1.5 mmol) and tetrakis(triphenylphosphine) palladium(5 mol %) were added. The reaction mixture was heated at 100 °C andthe progress of the reaction was checked by TLC until the starting materialwas consumed. The mixture was cooled to r.t., and the reactionwas quenched with sat. NH4Cl solution (5 mL). The mixture was extractedwith EtOAc, dried over anhydrous Na2SO4 and evaporated undervacuum. The residue was purified by flash column chromatographyto afford the desired product.

Reference： [1]Xu, Wan; Zeng, Meng-Tian; Liu, Min; Liu, Sha-Sha; Li, Yue-Sheng; Dong, Zhi-Bing [Synthesis, 2017, vol. 49, # 14, p. 3084 - 3090]

69
[ 302-17-0 ]
[ 2401-24-3 ]
(E)-N-(2-chloro-5-methoxyphenyl)-2-(hydroxyimino)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	With hydrogenchloride; hydroxylamine; sodium sulfate In water for 1.5h; Reflux; Inert atmosphere;	B.775.g g) (E)-N-(2-Chloro-5-methoxyphenyl)-2-(hydroxyimino)acetamide To a solution of 2-Chloro-5-methoxyaniline (8.00 g, 50.8 mmol) in water (72 mL) is added concentrated HCI (35%) (4.32 mL), then a solution of chloral hydrate (8.43 g, 51 mmol) in water (176 mL) followed by sodium sulfate (24.6 g, 156 mmol). Hydroxylamine (50% in water, 7.68 mL, 254 mmol) is added, and the mixture is refluxed for 1.5h. The RM is cooled to 000, the RM is filtered and the obtained precipitate is washed with water (x 3). The solid is dissolved in acetone and dried with MgSO4. The organic phase is filtered and thesolvent is removed under reduced pressure to afford a dark brown solid. It is triturated in Et20, the solid is removed by filtration, well washed with Et20 and discarded. The filtrate is concentrated to dryness. The resulting orange solid is triturated in DCM, the solid is filtered, and the filtrate is concentrated under vacuum, to be triturated again in DCM before being filtered (x 3). This affords the pure product as a beige solid (4.08 g, 35%). LCMS A: tR = 0.73 mi , [M+H]+=229.07.

Reference： [1]Current Patent Assignee: IDORSIA PHARMACEUTICALS LTD; JOHNSON & JOHNSON INC - WO2017/85198, 2017, A1 Location in patent: Page/Page column 218

70
[ 185-72-8 ]
[ 2401-24-3 ]
4-(((2-chloro-5-methoxyphenyl)amino)methyl)tetrahydro-2H-pyran-4-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With lithium perchlorate; In acetonitrile; at 90℃; for 18h;	General procedure: A mixture of benzyl 1-oxa-6-azaspiro[2.5]octane-6-carboxylate (247 mg, 1.0 mmol), 2-bromo-4-methoxyaniline (303 mg, 1.5 mmol) and lithium perchlorate (190 mg, 1.7 mmol) were taken in acetonitrile (3.0 mL). The reaction mixture was heated to 90 C for 18 h. The reaction mixture was diluted with ethyl acetate (20 mL) and washed with water. The organic layer was dried over sodium sulfate and concentrated under reduced pressure, and the product was purified by column chromatography (silica gel, 50% EtOAc/hexanes) to provide benzyl 4-(((2-bromo-4-methoxyphenyl)amino)methyl)-4-hydroxypiperidine-1-carboxylate, 5c (358 mg, 80%) as a colourless syrup.

Reference： [1]Tetrahedron Letters,2017,vol. 58,p. 3607 - 3611

71
[ 185-72-8 ]
[ 2401-24-3 ]
6-methoxy-2',3,3',4,5',6'-hexahydrospiro[benzo[b][1,4]oxazine-2,4'-pyran] [ No CAS ]

Reference： [1]Tetrahedron Letters,2017,vol. 58,p. 3607 - 3611

72
[ 2401-24-3 ]
[ 16420-13-6 ]
5-methoxy-N,N-dimethylbenzo[d]thiazol-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With potassium <i>tert</i>-butylate; bis(dibenzylideneacetone)-palladium⁽⁰⁾ In tetrahydrofuran at 60℃;	Typical procedure for the preparation of 2-aminobenzothiazoles in the presence of potassium tert-butoxideand Bis(dibenzylideneacetone) palladium (TP ) General procedure: A dried tube, equipped with a magnetic stirred and a septum, 2-chloroanilines (1.0 mmol) was dissolved in DMSO(3 mL), and t-BuOK (3 mmol) was added. The mixture was stirred for 5 minutes, and thendimethylthiocarbamoyl chloride (1.2 mmol) and bis(dibenzylideneacetone) palladium (5 mol%) were added.the reaction mixture was then heated at 100 °C and checked by TLC until the starting material was finished. Thereaction was cooled down to room temperature, and then quenched with sat. NH4Cl solution (5 mL) and extractedwith ethyl acetate, dried over anhydrous Na2SO4 and evaporated under vacuum. The residue was purified by flashcolumn chromatography to afford the desired product.

Reference： [1]Xu, Wan; Zeng, Meng-Tian; Liu, Min; Liu, Xing; Chang, Cai-Zhu; Zhu, Hui; Li, Yue-Sheng; Dong, Zhi-Bing [Chemistry Letters, 2017, vol. 46, # 5, p. 641 - 643]

73
[ 2401-24-3 ]
[ 1885-14-9 ]
C₁₄H₁₂ClNO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-chloro-5-methoxyaniline With triethylamine In dichloromethane at 20℃; for 0.166667h; Inert atmosphere; Stage #2: phenyl chloroformate In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere;	Synthesis of phenyl phenylcarbamate derivatives (5a-q) General procedure: To a stirred solution of anilines (3.29 mmol) in dichloromethane (6 mL) was added triethylamine (9.89 mmol) at room temperature and stirred at room temperature for 10 min and added aryl chloro formate (4.93 mmol) at 0 °C and stirred at room temperature for 2 h. The reaction mixture was concentrated under reduced pressure and the crude material washed with 10 % diethyl ether in pentane to afford the pure compounds. Without further purification used for next step. Yields of the products varied between 65 to 85 %.

Reference： [1]Bhasker, G Vijaya; Satyanarayana; Latha; Laxminarayana; Chary, M Thirumala [Asian Journal of Chemistry, 2018, vol. 30, # 4, p. 771 - 774]

74
[ 2401-24-3 ]
1,5-dimethylisoquinolin-6-yl trifluoromethanesulfonate [ No CAS ]
N-(2-chloro-5-methoxyphenyl)-1,5-dimethylisoquinolin-6-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With palladium diacetate; caesium carbonate; XPhos In toluene for 5h; Inert atmosphere; Reflux;	N-(2-Chloro-5-methoxyphenyl)-1,5-dimethylisoquinolin-6-amine (18b). 2-Chloro-5-methoxyaniline (17b, 92 L,0.74mmol) was added dropwise to a solution of 1,5-dimethylisoquinolin-6-yl trifluoromethanesulfonate(14, 0.15 g, 0.49 mmol), palladium(II) acetate (8.3 mg, 37 mol), XPhos (35 mg, 74 mol), and cesiumcarbonate (224 mg, 0.688 mmol) in toluene (12 mL). The mixture was heated at reflux for fivehours. After cooling to room temperature, the reaction mixture was filtered over a short padof Hyo (ethyl acetate), and the solvent was evaporated. Purication of the residue by columnchromatography (silica gel, dichloromethane/ethyl acetate, 1:1 to 0:1, each + 1% ethanol) providedN-(2-chloro-5-methoxyphenyl)-1,5-dimethylisoquinolin-6-amine (18b, 0.141 g, 0.451 mmol, 92%) asa beige solid. M.p. 135-138 °C; UV (MeOH): l = 224, 277, 322 nm; fluorescence (MeOH): lex = 224,lem = 301 (sh), 336 nm; IR (ATR): n = 3416, 3068, 2998, 2929, 2853, 1596, 1508, 1447, 1421, 1383, 1343,1312, 1287, 1230, 1207, 1170, 1138, 1069, 1027, 924, 820, 732, 671, 640 cm-1; 1H-NMR (500 MHz, CDCl3):d = 2.53 (s, 3H), 2.94 (s, 3H), 3.68 (s, 3H), 6.13 (br s, 1H), 6.40 (dd, J = 8.8, 2.8 Hz, 1H), 6.47 (d, J = 2.8 Hz,1H), 7.28 (d, J = 8.8 Hz, 1H), 7.53 (d, J = 9.0 Hz, 1H), 7.63 (d, J = 6.1 Hz, 1H), 7.97 (d, J = 9.0 Hz,1H), 8.39 (d, J = 6.1 Hz, 1H); 13C-NMR (125 MHz, CDCl3): d = 12.66 (CH3), 22.61 (CH3), 55.46 (CH3),101.82 (CH), 105.94 (CH), 113.40 (C), 115.53 (CH), 122.55 (CH), 123.53 (C), 124.67 (C), 124.76 (CH), 130.02(CH), 136.78 (C), 139.77 (C), 141.06 (CH), 142.38 (C), 158.64 (C), 159.20 (C); MS (EI): m/z (%) = 312(100, [M]+), 277 (80), 262 (76), 247 (13), 233 (18), 219 (12), 139 (10), 117 (16), 63 (10); MS (ESI, +10 V):m/z = 313.3 [M + H]+.

Reference： [1]Schmidt, Ulrike; Theumer, Gabriele; Jäger, Anne; Kataeva, Olga; Wan, Baojie; Franzblau, Scott G.; Knölker, Hans-Joachim [Molecules, 2018, vol. 23, # 6]

75
[ 2401-24-3 ]
[ 103-80-0 ]
N-(2-chloro-5-methoxyphenyl)-2-phenylacetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
657 mg	With triethylamine In acetonitrile at 0 - 0.35℃; for 0.5h;	49 Reference Example 49 To a solution of 2-chloro-5-methoxyaniline (500 mg) and TEA (0.49 mL) in MeCN (4 mL) was added phenylacetyl chloride (0.42 mL) at 0° C., and the mixture was stirred at room temperature for 30 minutes. To the reaction solution was added water, and the mixture was extracted with AcOEt and washed with brine. The organic layer was dried over anhydrous sodium sulfate, and then filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Hexane/AcOEt) to give N-(2-chloro-5-methoxyphenyl)-2-phenylacetamide (657 mg).

Reference： [1]Current Patent Assignee: OTSUKA HOLDINGS CO LTD - US2019/40039, 2019, A1 Location in patent: Paragraph 0496; 0542

76
[ 2401-24-3 ]
[ 60656-87-3 ]
[ 1246453-61-1 ]

Yield	Reaction Conditions	Operation in experiment
74%	Stage #1: 2-chloro-5-methoxyaniline; benzyloxyacetoaldehyde With acetic acid In dichloromethane at 23℃; for 0.25h; Inert atmosphere; Stage #2: With sodium tris(acetoxy)borohydride In dichloromethane at 23℃; for 18h; Inert atmosphere;

Reference： [1]Qiao, Luxi; Fisher, Emily; McMurray, Lindsay; Milicevic Sephton, Selena; Hird, Matthew; Kuzhuppilly-Ramakrishnan, Nisha; Williamson, David J.; Zhou, Xiouyun; Werry, Eryn; Kassiou, Michael; Luthra, Saijinder; Trigg, William; Aigbirhio, Franklin I. [ChemMedChem, 2019, vol. 14, # 9, p. 982 - 993]

77
[ 2401-24-3 ]
[ 19654-14-9 ]
N-(3-(benzo[d]thiazol-2-yl)phenyl)-2-chloro-5-methoxyaniline [ No CAS ]

Reference： [1]Bioorganic and medicinal chemistry letters,2020

78
[ 24424-99-5 ]
[ 2401-24-3 ]
tert-butyl (2-chloro-5-methoxyphenyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hexamethyldisilazane In tetrahydrofuran at 25℃; for 1h;	Tert-butyl (2-chloro-5-methoxyphenyl)carbamate (2): 2-chloro-5-methoxyaniline (5.00g; 31.73mmol; 1.00 equivalent [eq.]), tetrahydrofuran (THF; 79.32mL) and Di-tert-butyl pyrocarbonate (Boc2O; 7.62g; 34.90mmol; 1.10 eq.) were placed in a round bottom flask with a stir bar. Sodium bis(trimethylsilyl) amide (NaHMDS; 63.45mL; 1.00mol/L; 63.45mmol; 2.00 eq.) was added gradually to the flask while the temperature of the mixture was maintained below 0°C. The resulting viscous brown solution was warmed to room temperature (25°C) and stirred for an additional hour. The mixture was then cooled back to 0°C and quenched by the slow addition of water (30mL). The aqueous layer was separated and further extracted with ethyl acetate (EtOAc [3×25mL]). The EtOAc extraction and the previous organic layer were pooled together, washed with brine, dried over magnesium sulfate (MgSO4), filtered and condensed into an orange-colored oil. The compound was purified by column chromatography (220g silica gel, 0-30% EtOAc:heptane). The product containing fractions were condensed into a pale, yellow oil. 1H nuclear magnetic resonance (NMR) (400MHz, CHLOROFORM-d) d=7.87 (d, J=2.7Hz, 1H), 7.22 (d, J=8.9Hz, 1H), 7.02 (br s, 1H), 6.55 (dd, J=2.9, 8.8Hz, 1H), 3.83 (s, 3H), 1.56 (s, 9H).

Reference： [1]Breitenbucher, James Guy; Chen, Jie; Chen, Mi; Chung, DeMichael; Gu, Guibao; Heger, Lindsay; Keenan, Terence; Renick, Joel; Santora, Vincent J.; Scott, Trevor; Stauber, Kathe; Tabatabaei, Ali; Vivian, Jeffrey; Zook, Douglas [Neurochemistry International, 2020, vol. 137]

79
[ 2401-24-3 ]
[ 75-26-3 ]
2-chloro-N-isopropyl-5-methoxyaniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	Stage #1: 2-chloro-5-methoxyaniline With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 1.5h; Inert atmosphere; Stage #2: isopropyl bromide In tetrahydrofuran; mineral oil for 1h; Reflux;

Reference： [1]Deng, Zhuofei; Li, Ridong; Lin, Yicao; Luo, Zhonghua; Sun, Guodong; Wang, Zhongqing; Zhang, Jiancun [Journal of Organic Chemistry, 2020, vol. 85, # 16, p. 10584 - 10592]

80
[ 111-83-1 ]
[ 2401-24-3 ]
2-chloro-5-methoxy-N-octylaniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	Stage #1: 2-chloro-5-methoxyaniline With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 1.5h; Inert atmosphere; Stage #2: 1-bromo-octane In tetrahydrofuran; mineral oil for 1h; Reflux;

Reference： [1]Deng, Zhuofei; Li, Ridong; Lin, Yicao; Luo, Zhonghua; Sun, Guodong; Wang, Zhongqing; Zhang, Jiancun [Journal of Organic Chemistry, 2020, vol. 85, # 16, p. 10584 - 10592]

81
[ 534-00-9 ]
[ 2401-24-3 ]
(S)-2-chloro-5-methoxy-N-(2-methylbutyl)aniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	Stage #1: 2-chloro-5-methoxyaniline With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 1.5h; Inert atmosphere; Stage #2: (S)-2-methylbutyl bromide In tetrahydrofuran; mineral oil for 1h; Reflux;

Reference： [1]Deng, Zhuofei; Li, Ridong; Lin, Yicao; Luo, Zhonghua; Sun, Guodong; Wang, Zhongqing; Zhang, Jiancun [Journal of Organic Chemistry, 2020, vol. 85, # 16, p. 10584 - 10592]

82
[ 2401-24-3 ]
[ 106-94-5 ]
[ 1247606-65-0 ]

Yield	Reaction Conditions	Operation in experiment
93%	Stage #1: 2-chloro-5-methoxyaniline With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 1.5h; Inert atmosphere; Stage #2: propyl bromide In tetrahydrofuran; mineral oil for 1h; Reflux;

Reference： [1]Deng, Zhuofei; Li, Ridong; Lin, Yicao; Luo, Zhonghua; Sun, Guodong; Wang, Zhongqing; Zhang, Jiancun [Journal of Organic Chemistry, 2020, vol. 85, # 16, p. 10584 - 10592]

83
[ 1147088-78-5 ]
[ 2401-24-3 ]
C₄₂H₄₆BCl₂N₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With bis[2-(diphenylphosphino)phenyl] ether; bis(dibenzylideneacetone)-palladium⁽⁰⁾; sodium t-butanolate In toluene at 100℃; for 20h; Inert atmosphere; Schlenk technique;	Buchwald-Hartwig amination of dibenzoazaborine 1 (representative procedure) General procedure: A toluene (5 mL) solution of 1 (0.55 g, 1.0 mmol), 2-chloroaniline (2a) (0.23 mL, 2.2mmol), [Pd(dba)2] (0.12 g, 0.20 mmol, 20 mol%), DPE-phos (0.11 g, 0.20 mmol, 20 mol%),tBuONa (0.48 g, 5.0 mmol) was stirred at 100 °C for 20 h. The reaction was quenched with aq.NH4Cl, and the mixture was extracted with CHCl3. The organic layer was dried over Na2SO4and concentrated to afford a crude material, which was subjected to chromatography (Al2O3,CH2Cl2/hexane = 1:1) followed by reprecipitation of the CHCl3 solution in MeOH(100 mL) togive 3a as a yellow solid (0.37 g, 0.57 mmol, 57 %)

Reference： [1]Nagata, Masakazu; Oshiro, Taku; Mizuhata, Yoshiyuki; Tokitoh, Norihiro; Hosoya, Takaaki; Yamada, Shigeyuki; Konno, Tsutomu; Fukumoto, Hiroki; Kubota, Toshio; Agou, Tomohiro [Bulletin of the Chemical Society of Japan, 2020, vol. 94, # 1, p. 21 - 23]

84
[ 2401-24-3 ]
[ 15216-81-6 ]
C₁₄H₁₁Cl₂NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine at 90℃; for 2h;	b) General procedure: 5-chloro-2-hydroxybenzoyl chloride (0.166 g, 0.869 mmol) and 4-nitroaniline (.060 g, 0.434 mmol) were suspended in Pyridine (1.5 mL) and stirred at room temperature for 1h. After this time it was heated at 90 C for 2h. The reaction mixture was then cooled to room temperature, diluted with EtOAc (20 mL), washed with 10% CuSO4 solution (20 mL), washed with 1N HCl solution, separated from aqueous layer, dried and concentrated to give the crude product which was purified by reverse phase HPLC.

Reference： [1]Shamim, Khalida; Xu, Miao; Hu, Xin; Lee, Emily M; Lu, Xiao; Huang, Ruili; Shah, Pranav; Xu, Xin; Chen, Catherine Z.; Shen, Min; Guo, Hui; Chen, Lu; Itkin, Zina; Eastman, Richard T.; Shinn, Paul; Klumpp-Thomas, Carleen; Michael, Sam; Simeonov, Anton; Lo, Donald C.; Ming, Guo-li; Song, Hongjun; Tang, Hengli; Zheng, Wei; Huang, Wenwei [Bioorganic and Medicinal Chemistry Letters, 2021, vol. 40]

85
[ 39110-32-2 ]
[ 2401-24-3 ]
N-(2-chloro-5-methoxyphenyl)-3-hydroxynaphthalene-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	With phosphorus trichloride In chlorobenzene at 100 - 130℃; for 0.75h; Microwave irradiation;	General Procedure for the Synthesis of N-(Disubstituted phenyl)-3-hydroxynaphthalene-2-carboxamides 1-24 General procedure: 3-Hydroxynaphthalene-2-carboxylic acid (0.5 g, 2.65 mM) was suspended in drychlorobenzene (20 mL) at ambient temperature and phosphorus trichloride (0.12 mL,1.35 mM), and the corresponding substituted aniline (2.65 mM) was added dropwise.The reaction mixture was transferred to the microwave reactor, where the synthesis wasperformed (1st phase: 10 min, 100 C; 2nd phase: 15 min, 120 C; 3rd phase: 20 min, 130 C;max 500 W). The mixture was then cooled to 60 C, and the solvent was removed underreduced pressure. The residue was washed sequentially with hydrochloric acid and water,and the crude product was recrystallized from EtOH. All the compounds are presented inTable 1.

Reference： [1]Gonec, Tomas; Jampilek, Josef; Jendrzejewska, Izabela; Kos, Jiri; Oravec, Michal [Molecules, 2021, vol. 26, # 14]

86
[ 2065-37-4 ]
[ 2401-24-3 ]
2-((2-chloro-5-methoxyphenyl)amino)naphthalene-1,4-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59%	With tripotassium phosphate tribasic; palladium diacetate; N-[2'-(dicyclohexylphosphino)-1,1'-biphenyl-2-yl]-N,N-dimethylamine In 1,4-dioxane at 120℃; for 0.5h; Microwave irradiation; Inert atmosphere; Sealed tube; regioselective reaction;

Reference： [1]Burley, Glenn A.; Bush, Jacob T.; Campbell, Emma; Kennedy, Alan R.; Paisley, Olivia I.; Taladriz-Sender, Andrea [Journal of Organic Chemistry, 2022, vol. 87, # 7, p. 4603 - 4616]

87
[ 2065-37-4 ]
[ 2401-24-3 ]
3-methoxy-5H-benzo[b]carbazole-6,11-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With tripotassium phosphate tribasic; palladium diacetate; N-[2'-(dicyclohexylphosphino)-1,1'-biphenyl-2-yl]-N,N-dimethylamine In 1,4-dioxane at 120 - 160℃; for 8.5h; Microwave irradiation; Inert atmosphere; Sealed tube; regioselective reaction;

Reference： [1]Burley, Glenn A.; Bush, Jacob T.; Campbell, Emma; Kennedy, Alan R.; Paisley, Olivia I.; Taladriz-Sender, Andrea [Journal of Organic Chemistry, 2022, vol. 87, # 7, p. 4603 - 4616]

88
[ 92-66-0 ]
[ 2401-24-3 ]
N-(2-chloro-5-methoxyphenyl)[1,1'-biphenyl]-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With Pd[t-Bu₂P(4-NMe₂C₆H₄)]₂Cl₂; sodium tertiary butoxide In 1-methyl-pyrrolidin-2-one at 100℃; for 9h; Inert atmosphere;	1-3 Example 3 Under the protection of argon, in 2L with mechanical stirring, thermometer,In the there-necked flask of the heating reaction device, add 2-chloro-5-methoxyaniline 157.6g (1mol),233.1 g (1 mol) of 4-bromobiphenyl, 96.1 g (1 mol) of sodium tert-butoxide, and 2 L of N-methylpyrrolidone were added.After passing through argon protection, 7.1 g (0.01 mol) of dichlorodi-tert-butyl-(4-dimethylaminophenyl) phosphorus palladium (II) was added as a catalyst,The reaction temperature was controlled to be 100 °C, and the reaction was continued for 9 hours at a constant temperature, and the 4-bromobiphenyl reaction was detected by high performance liquid chromatography.

Reference： [1]Current Patent Assignee: HENAN ACADEMY OF SCIENCES - CN114031545, 2022, A Location in patent: Paragraph 0019; 0020; 0025; 0026; 0028; 0029

Same Skeleton Products

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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