[ CAS No. 13194-68-8 ] {[proInfo.proName]}

Name: 13194-68-8|4-Iodo-2-methylaniline|98%
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Quality Control of [ 13194-68-8 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 13194-68-8 ]

CAS No. :	13194-68-8	MDL No. :	MFCD00025299
Formula :	C₇H₈IN	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	BGKLFAQCHHCZRZ-UHFFFAOYSA-N
M.W :	233.05	Pubchem ID :	83221
Synonyms :

Calculated chemistry of [ 13194-68-8 ]

Physicochemical Properties

Num. heavy atoms :	9
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.14
Num. rotatable bonds :	0
Num. H-bond acceptors :	0.0
Num. H-bond donors :	1.0
Molar Refractivity :	48.53
TPSA :	26.02 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) :	-6.32 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.83
Log Po/w (XLOGP3) :	1.97
Log Po/w (WLOGP) :	2.19
Log Po/w (MLOGP) :	2.72
Log Po/w (SILICOS-IT) :	2.55
Consensus Log Po/w :	2.25

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.02
Solubility :	0.223 mg/ml ; 0.000956 mol/l
Class :	Soluble
Log S (Ali) :	-2.14
Solubility :	1.68 mg/ml ; 0.00721 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.38
Solubility :	0.0965 mg/ml ; 0.000414 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.43

Safety of [ 13194-68-8 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302+H312+H332-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 13194-68-8 ]

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

Upstream synthesis route of [ 13194-68-8 ]
Downstream synthetic route of [ 13194-68-8 ]

[ 13194-68-8 ] Synthesis Path-Upstream 1~11

1
[ 13194-68-8 ]
[ 55919-82-9 ]

Yield	Reaction Conditions	Operation in experiment
99%	With acetic acid; sodium nitrite In water for 6 h;	A solution of 4-iodo-2-methylaniline (10.0 g, 42.9 mmol) in glacial acetic acid (400 mL) was treated with a solution of NaNO₂(2.96 g, 42.9 mmol) in water (10 mL). After stirring for 6 hours, the mixture was concentrated to dryness and dissolved in ethyl acetate (EtOAc). Filtration through a pad of silica gel (EtOAc) provided the title compound (10.4 g, 99percent) as a deep purple solid: ESI MS m/z 245 [M+H]⁺.

Reference： [1] Patent: US2009/82359, 2009, A1, . Location in patent: Page/Page column 47
[2] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 11, p. 3177 - 3180
[3] Patent: US2012/71535, 2012, A1, . Location in patent: Page/Page column 53-54
[4] Patent: WO2008/154241, 2008, A1,

2
[ 13194-68-8 ]
[ 5326-47-6 ]

Reference： [1] American Chemical Journal, 1909, vol. 42, p. 500

3
[ 583-75-5 ]
[ 13194-68-8 ]

Yield	Reaction Conditions	Operation in experiment
90%	With copper(l) iodide; sodium iodide; N,N`-dimethylethylenediamine In 1,4-dioxane at 110℃; for 18 h; Inert atmosphere; Schlenk technique	Aromatic Finkelstein Reaction; General ProcedureThe reaction was carried out under argon using standard Schlenktechniques due to the moisture and oxygen sensitivity of the copper(I) iodide. A two-neck pear-shaped flask equipped with a refluxcondenser was charged with the (het)aryl bromide starting material,NaI (2 equiv per bromine to exchange), and CuI (5 molpercent per bromineto exchange). N,N′-Dimethylethylenediamine (L1) or N,N′-dimethyl-1,2-cyclohexanediamine (L2) (10 molpercent per bromine toexchange) and anhydrous 1,4-dioxane (0.5 mL per 1 mmol NaI)were added. The resulting suspension was heated to 110 °C for 18h. After cooling to r.t., the mixture was poured into aq 25percent NH3 solution.The blue solution was diluted to a doubled volume with H2Oand was extracted three times with CH2Cl2. In the case of the 2,2′-bipyridines, the combined organic phases were additionally washedwith aq EDTA solution. Otherwise, the combined organic phaseswere solely washed with brine and dried with MgSO4. The solventwas removed under reduced pressure to give the desired product inpure form. If needed, the crude product can be purified by columnchromatography or recrystallization.

Reference： [1] Synthesis (Germany), 2014, vol. 46, # 8, p. 1085 - 1090
[2] Journal of the American Chemical Society, 2015, vol. 137, # 26, p. 8328 - 8331

4
[ 95-53-4 ]
[ 13194-68-8 ]

Yield	Reaction Conditions	Operation in experiment
93%	With 1,4-dibenzyl-1,4-diazoniabicyclo[2.2.2]octane dichloroiodate In neat (no solvent) at 20℃; for 0.166667 h;	General procedure: General procedure for the iodination of aryl amines under solvent-free conditions.DBDABCODCI (0.5 mmol) and aryl amine (1 mmol) were triturated together in a porcelainmortar at room temperature. After completing reaction which monitored by TLC, the ethylacetate added to mixture and filtered, the organic layer washed with 5percent aqueous sodiumthiosulfate, and dried over MgSO4. The solvent was removed in vacuum and the crude mixturewas purified by column chromatography using ethyl acetate and hexane mixture and analyzedby m.p. and 1H NMR spectroscopy.
73%	With iodine; sodium carbonate In cyclohexane; water at 20℃; for 3 h;	General procedure: To a clean 50 mL round bottomed flask equipped with a large stir bar was added the substrate (10 mmol) followed by cyclohexane (ca. 6.0 mL to maintain the reaction concentration of 1.67 M) and an aqueous saturated solution of sodium carbonate (2.8 mL). Finally, iodine beads (11 mmol) were added as a solid and the flask was sealed with a septum and vented with a needle to the open atmosphere. The reaction was allowed to stir for the specified time at room temperature unless otherwise noted (see refPreviewPlaceHolderTable 1). The reaction mixture was poured into a separatory funnel with the aid of ethyl acetate or MTBE (2-3 mL) with additional aqueous saturated sodium carbonate (1 mL). The organic layer was washed twice with an aqueous saturated solution of sodium bisulfite (4 mL) and brine (5 mL), dried over sodium sulfate, and concentrated in vacuo to provide crude iodinated product. The products were purified by crystallization (if crystalline) from hexanes. Column chromatography (ethyl acetate/hexanes) was performed on the oils.

Reference： [1] Bulletin of the Chemical Society of Ethiopia, 2015, vol. 29, # 1, p. 157 - 162
[2] Bulletin of the Chemical Society of Japan, 1988, vol. 61, # 2, p. 600 - 602
[3] Molecules, 2002, vol. 7, # 12, p. 867 - 870
[4] Synthesis, 2004, # 3, p. 441 - 445
[5] Synthetic Communications, 2012, vol. 42, # 16, p. 2407 - 2414
[6] Journal of the Iranian Chemical Society, 2012, vol. 9, # 3, p. 321 - 326
[7] Molecules, 2005, vol. 10, # 10, p. 1307 - 1317
[8] Synthetic Communications, 2013, vol. 43, # 21, p. 2913 - 2925
[9] Tetrahedron Letters, 2011, vol. 52, # 52, p. 7141 - 7145
[10] Journal of the Chinese Chemical Society, 1996, vol. 43, # 1, p. 95 - 99
[11] Molecules, 2004, vol. 9, # 7, p. 617 - 621
[12] Patent: CN103497211, 2016, B, . Location in patent: Paragraph 0068; 0069
[13] Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical & Analytical, 1987, vol. 26, # 4, p. 333 - 335
[14] American Chemical Journal, 1909, vol. 42, p. 500
[15] Zhurnal Obshchei Khimii, 1953, vol. 23, p. 663,666; engl. Ausg. S. 689, 691
[16] Journal of the American Chemical Society, 1925, vol. 47, p. 1711
[17] Journal of the American Chemical Society, 1941, vol. 63, p. 436
[18] Catalysis Letters, 2010, vol. 137, # 3-4, p. 190 - 201
[19] Synlett, 2012, # 2, p. 208 - 214
[20] Chemical Communications, 2014, vol. 50, # 17, p. 2136 - 2138
[21] RSC Advances, 2015, vol. 6, # 1, p. 403 - 408

5
[ 95-53-4 ]
[ 13194-68-8 ]

Reference： [1] Tetrahedron Letters, 2007, vol. 48, # 35, p. 6124 - 6128
[2] Synthetic Communications, 2008, vol. 38, # 22, p. 3894 - 3902
[3] Synlett, 2012, # 2, p. 208 - 214

6
[ 52415-00-6 ]
[ 13194-68-8 ]

Reference： [1] Monatshefte fuer Chemie, 1905, vol. 26, p. 1103

7
[ 120-66-1 ]
[ 13194-68-8 ]

Reference： [1] Journal fuer Praktische Chemie (Leipzig), 1906, vol. <2> 74, p. 314
[2] Chemische Berichte, 1907, vol. 40, p. 4084

8
[ 611-05-2 ]
[ 13194-68-8 ]

Reference： [1] Monatshefte fuer Chemie, 1905, vol. 26, p. 1103

9
[ 100377-05-7 ]
[ 95-53-4 ]
[ 13194-68-8 ]

Reference： [1] Zhurnal Obshchei Khimii, 1956, vol. 26, p. 3139,3143; engl. Ausg. S. 3499, 3503

10
[ 13194-68-8 ]
[ 78881-21-7 ]

Yield	Reaction Conditions	Operation in experiment
69.34%	at 150 - 160℃; for 12 h;	4-iodo-2-methylaniline (2000mg, 8.58mmol) and cyanide(1.15g, 12.87mmol, 1.5eq)were added to pyridine. A reaction mixture was heated to 150~160 °C and stirred for 12hrs. A reaction mixture was diluted with methylene chloride. A diluted solution was washed with copper sulfate for several times. A mixture was washed with H₂O (2 times) and brine, and then dried over Na₂SO₄. A residue was purified with column chromatography (n-Hexane : EtOAc =2 : 1) to yield a solid (786.5mg, 69.34percent). Mp: 78-80 °C; IR(NaCl neat, cm-¹): 3403, 3335, 3220, 2942, 2220; ¹H NMR(400MHz, CDCl₃): 7.24(m, 2H), 6.57(d, 1 H, J=8.4Hz), 4.03(bs, 2H), 2.08(s, 9H).

Reference： [1] Patent: EP1862454, 2007, A1, . Location in patent: Page/Page column 17

11
[ 13194-68-8 ]
[ 544-92-3 ]
[ 78881-21-7 ]

Yield	Reaction Conditions	Operation in experiment
69.34%	at 150 - 160℃; for 12 h;	Example 8: N-{4-[3-(4-tert-Butyl-benzyl)-ureidomethyl]-2-methyl-6-vinyl-phenyl}-methanesulfonamide; EPO <DP n="91"/>Step 1 : 4-Amino-3-methylbenzonitrile; 4-iodo-2-methylaniline (2000mg, 8.58mmol) and cyanide(1.15g, 12.87mmol, 1.5eq)were added pyridine. A reaction mixture was heated to 150~160°C , stirred for 12hr. A reaction mixture was diluted with methylene chloride. A diluted solution was washed with copper sulfate for several times. A mixture was washed with H₂O (2 times) and b.rine, and then dried with Na₂SO₄. A residue was purified with column chromatography (n-Hexane: EtOAc =2 : 1 ) to yield solid (786.5mg, 69.34percent).mp: 78-80 °C ;IR(NaCI neat, cm^"1) : 3403, 3335, 3220, 2942, 2220;¹H NMR(400MHz, CDCI₃): 7.24(m, 2H), 6.57(d, 1H, J=8.4Hz), 4.03(bs, 2H), 2.08(s, 9H).

Reference： [1] Patent: WO2006/101318, 2006, A1, . Location in patent: Page/Page column 90

[ 13194-68-8 ] Synthesis Path-Downstream 1~52

1
[ 13194-68-8 ]
[ 227015-67-0 ]

Yield	Reaction Conditions	Operation in experiment
19%		A solution of NaNO2 (2.96 g, 42.9 mmol) in water (30 mL) was added to a mixture of 4-iodo-2- methyl-aniline (which is available from Aldrich; 5 g, 21.5 mmol) and HC1 (30 mL) at -5 C. Themixture was stilTed at -5 C for 45 mi Tin(II) chloride dihydrate (24.1 g, 107 mmol) was added and the mixture was stirred for 30 mm. The mixture was made alkaline by adding aqueous NaOH solution. The solid was filtered off and purified by chromatography (silica gel) to give (4- iodo-2-methyl-phenyl)-hydrazine (1 g, 19%). ?H NMR (300 MHz, DMSO-d6), oe ppm 7.33 (dd, J=8.5, 2.1 Hz, 1 H), 7.23 (d, J=1.3 Hz, 1 H), 6.87 (d, J=8.5 Hz, 1 H), 6.37 (s, 1 H), 3.98 (s, 2 H),2.01 (s, 3 H, overlapping with CH3 peak from residual EtOAc solvent). MS calcd. for C7H,01N2 ([M+H]j: 249, obsd. 231.8.

Reference： [1]Patent: WO2015/86642,2015,A1 .Location in patent: Page/Page column 101
[2]Journal fur praktische Chemie (Leipzig 1954),1906,vol. <2> 74,p. 314

2
[ 52415-00-6 ]
[ 13194-68-8 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonia; water; iron(II) sulfate at 60 - 70℃;

Reference： [1]Artmann [Monatshefte fur Chemie, 1905, vol. 26, p. 1103]

3
[ 95-53-4 ]
[ 13194-68-8 ]

Yield	Reaction Conditions	Operation in experiment
93%	With 1,4-dibenzyl-1,4-diazoniabicyclo[2.2.2]octane dichloroiodate; In neat (no solvent); at 20℃; for 0.166667h;	General procedure: General procedure for the iodination of aryl amines under solvent-free conditions.DBDABCODCI (0.5 mmol) and aryl amine (1 mmol) were triturated together in a porcelainmortar at room temperature. After completing reaction which monitored by TLC, the ethylacetate added to mixture and filtered, the organic layer washed with 5% aqueous sodiumthiosulfate, and dried over MgSO4. The solvent was removed in vacuum and the crude mixturewas purified by column chromatography using ethyl acetate and hexane mixture and analyzedby m.p. and 1H NMR spectroscopy.
73%	With iodine; sodium carbonate; In cyclohexane; water; at 20℃; for 3h;	General procedure: To a clean 50 mL round bottomed flask equipped with a large stir bar was added the substrate (10 mmol) followed by cyclohexane (ca. 6.0 mL to maintain the reaction concentration of 1.67 M) and an aqueous saturated solution of sodium carbonate (2.8 mL). Finally, iodine beads (11 mmol) were added as a solid and the flask was sealed with a septum and vented with a needle to the open atmosphere. The reaction was allowed to stir for the specified time at room temperature unless otherwise noted (see refPreviewPlaceHolderTable 1). The reaction mixture was poured into a separatory funnel with the aid of ethyl acetate or MTBE (2-3 mL) with additional aqueous saturated sodium carbonate (1 mL). The organic layer was washed twice with an aqueous saturated solution of sodium bisulfite (4 mL) and brine (5 mL), dried over sodium sulfate, and concentrated in vacuo to provide crude iodinated product. The products were purified by crystallization (if crystalline) from hexanes. Column chromatography (ethyl acetate/hexanes) was performed on the oils.
67.9%	With Iodine monochloride; acetic acid;	The 1.62gICl (10mmol) dissolved in 10mLHOAc slowly dropwise added to the solution under stirring state containing 1.07g2-methylaniline (10mmol) dissolved in 10mLHOAc in solution, reaction sleepovers, reaction the fluid leans precipitates in a water, filtered, dry solid powdered toner [...] 1.58g, yield 67.9%.

Reference： [1]Bulletin of the Chemical Society of Ethiopia,2015,vol. 29,p. 157 - 162
[2]Bulletin of the Chemical Society of Japan,1988,vol. 61,p. 600 - 602
[3]Molecules,2002,vol. 7,p. 867 - 870
[4]Synthesis,2004,p. 441 - 445
[5]Synthetic Communications,2012,vol. 42,p. 2407 - 2414
[6]Journal of the Iranian Chemical Society,2012,vol. 9,p. 321 - 326
[7]New Journal of Chemistry,2019,vol. 43,p. 6001 - 6009
[8]Molecules,2005,vol. 10,p. 1307 - 1317
[9]Synthetic Communications,2013,vol. 43,p. 2913 - 2925
[10]Tetrahedron Letters,2011,vol. 52,p. 7141 - 7145
[11]Journal of the Chinese Chemical Society,1996,vol. 43,p. 95 - 99
[12]Molecules,2004,vol. 9,p. 617 - 621
[13]Patent: CN103497211,2016,B .Location in patent: Paragraph 0068; 0069
[14]Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical and Analytical,1987,vol. 26,p. 333 - 335
[15]American Chemical Journal,1909,vol. 42,p. 500
[16]Zhurnal Obshchei Khimii,1953,vol. 23,p. 663,666; engl. Ausg. S. 689, 691
[17]Journal of the American Chemical Society,1925,vol. 47,p. 1711
[18]Journal of the American Chemical Society,1941,vol. 63,p. 436
[19]Catalysis Letters,2010,vol. 137,p. 190 - 201
[20]Synlett,2012,p. 208 - 214
[21]Chemical Communications,2014,vol. 50,p. 2136 - 2138
[22]RSC Advances,2015,vol. 6,p. 403 - 408

4
[ 320-72-9 ]
[ 13194-68-8 ]
[ 90425-98-2 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1984,vol. 32,p. 305 - 312

5
[ 13194-68-8 ]
[ 133-91-5 ]
[ 90426-00-9 ]

Yield	Reaction Conditions	Operation in experiment
91%	With phosphorus trichloride In xylene at 140℃; for 4h;

Reference： [1]Ozawa; Takeuchi; Yamamoto; Hamada; Ito; Kuwahara; Takagaki [Chemical and Pharmaceutical Bulletin, 1984, vol. 32, # 1, p. 305 - 312]

6
[ 13194-68-8 ]
[ 61079-72-9 ]
[ 212628-45-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 6171 - 6174
[2]Synthetic Communications,2002,vol. 32,p. 411 - 417
[3]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 6501 - 6504

7
[ 13194-68-8 ]
[ 212631-85-1 ]
[ 212628-46-1 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; lithium diisopropyl amide; In tetrahydrofuran; n-heptane;	(b) Preparation of 5-Bromo-3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-benzoic acid To a stirred solution comprised of 1.88 g (0.00791 mol) of 2-amino-5-iodotoluene in 10 mL of tetrahydrofuran at -78 C. was added 6 mL (0.012 mol) of a 2.0 M lithium diisopropylamide in tetrahydrofuran/heptane/ethylbenzene (Aldrich) solution. The resulting green suspension was stirred vigorously for 10 minutes, after which time a solution of 1.00 g (0.00392 mol) of 5-bromo-2,3,4-trifluorobenzoic acid in 15 mL of tetrahydrofuran was added. The cold bath was subsequently removed, and the reaction mixture stirred for 18 hours. The mixture was concentrated, and the concentrate was treated with 100 mL of dilute (10%) aqueous hydrochloric acid. The resulting suspension was extracted with ether (2*150 mL), and the combined organic extractions were dried (MgSO4) and concentrated in vacuo to give an orange solid. The solid was triturated with boiling dichloromethane, cooled to ambient temperature, and collected by filtration. The solid was rinsed with dichloromethane, and dried in the vacuum-oven (80 C.) to afford 1.39 g (76%) of a yellow-green powder; mp 259.5-262 C.; 1H NMR (400 MHz, DMSO): delta9.03 (s, 1H), 7.99 (dd, 1H, J=7.5, 1.9 Hz), 7.57 (dd, 1H, J=1.5 Hz), 7.42 (dd, 1H, J=8.4, 1.9 Hz), 6.70 (dd, 1H, J=8.4, 6.0 Hz), 2.24 (s, 3H); 19F NMR (376 MHz, DMSO): delta-123.40 to -123.47 (m); -139.00 to -139.14 (m); IR (KBr) 1667 (C=O stretch)cm-1; MS (CI) M+1=469. Analysis calculated for C14H9BrF2INO2: C, 35.93; H, 1.94; N, 2.99; Br, 17.07; F, 8.12; I, 27.11. Found: C, 36.15; H, 1.91; N, 2.70; Br, 16.40; F, 8.46; I, 26.05.
	With hydrogenchloride; lithium diisopropyl amide; In tetrahydrofuran; n-heptane;	(b) Preparation of 5-Bromo-3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-benzoic acid To a stirred solution comprised of 1.88 g (0.00791 mol) of 2-amino-5-iodotoluene in 10 mL of tetrahydrofuran at -78 C. was added 6 mL (0.012 mol) of a 2.0 M lithium diisopropylamide in tetrahydrofuran/heptane/ethylbenzene (Aldrich) solution. The resulting green suspension was stirred vigorously for 10 minutes, after which time a solution of 1.00 g (0.00392 mol) of 5-bromo-2,3,4-trifluorobenzoic acid in 15 mL of tetrahydrofuran was added. The cold bath was subsequently removed, and the reaction mixture stirred for 18 hours. The mixture was concentrated, and the concentrate was treated with 100 mL of dilute (10%) aqueous hydrochloric acid. The resulting suspension was extracted with ether (2*150 mL), and the combined organic extractions were dried (MgSO4) and concentrated in vacuo to give an orange solid. The solid was triturated with boiling dichloromethane, cooled to ambient temperature, and collected by filtration. The solid was rinsed with dichloromethane, and dried in the vacuum-oven (80 C.) to afford 1.39 g (76%) of a yellow-green powder, mp 259.5-262 C.; 1H NMR (400 MHz, DMSO): delta 9.03 (s, 1H), 7.99 (dd, 1H, J=7.5, 1.9 Hz), 7.57 (dd, 1H, J=1.5 Hz), 7.42 (dd, 1H, J=8.4, 1.9 Hz), 6.70 (dd, 1H, J=8.4, 6.0 Hz), 2.24 (s, 3H); 19F NMR (376 MHz, DMSO): delta -123.40 to -123.47 (m); -139.00 to -139.14 (m); IR (KBr) 1667 (C=O stretch)cm-1; MS (CI) M+1=469.
	With hydrogenchloride; lithium diisopropyl amide; In tetrahydrofuran; n-heptane;	(b) Preparation of 5-Bromo-3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-benzoic Acid To a stirred solution comprised of 1.88 g (0.00791 mol) of 2-amino-5-iodotoluene in 10 mL of tetrahydrofuran at -78 C. was added 6 MnL (0.012 mol) of a 2.0 M lithium diisopropylamide in tetrahydrofuran/heptane/ethylbenzene (Aldrich) solution. The resulting green suspension was stirred vigorously for 10 minutes, after which time a solution of 1.00 g (0.00392 mol) of 5-bromo-2,3,4-trifluorobenzoic acid in 15 mL of tetrahydrofuran was added. The cold bath was subsequently removed, and the reaction mixture stirred for 18 hours. The mixture was concentrated, and the concentrate was treated with 100 mL of dilute (10%) aqueous hydrochloric acid. The resulting suspension was extracted with ether (2*150 mL), and the combined organic extractions were dried (MgSO4) and concentrated in vacuo to give an orange solid. The solid was triturated with boiling dichloromethane, cooled to ambient temperature, and collected by filtration. The solid was rinsed with dichloromethane, and dried in the vacuum-oven (80 C.) to afford 1.39 g (76%) of a yellow-green powder; mp 259.5-262 C.; 1H NMR (400 MHz, DMSO): delta 9.03 (s, 1H), 7.99 (dd, 1H, J=7.5, 1.9 Hz), 7.57 (dd, 1H, J=1.5 Hz), 7.42 (dd, 1H, J=8.4, 1.9 Hz), 6.70 (dd, 1H, J=8.4, 6.0 Hz), 2.24 (s, 3H); 19F NMR (376 MHz, DMSO): delta -123.40 to -123.47 (m); -139.00 to -139.14 (m); IR (KBr) 1667 (C=O stretch)cm-1; MS (CI) M+1=469. Analysis calculated for C14H9BrF2INO2: C, 35.93; H, 1.94; N, 2.99; Br, 17.07; F, 8.12; I, 27.11. Found: C, 36.15; H, 1.91; N, 2.70; Br, 16.40; F, 8.46; I, 26.05.

	With hydrogenchloride; lithium diisopropyl amide; In tetrahydrofuran; n-heptane;	Preparation 1 5-Bromo-3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-benzoic acid To a stirred solution comprised of 1.88 g (0.00791 mol) of 2-amino-5-iodotoluene in 10 mL of tetrahydrofuran at -78 C. was added 6 mL (0.012 mol) of a 2.0 M lithium diisopropylamide in tetrahydrofuran/heptane/ethylbenzene (Aldrich) solution. The resulting green suspension was stirred vigorously for 10 minutes, after which time a solution of 1.00 g (0.00392 mol) of 5-bromo-2,3,4-trifluorobenzoic acid in 15 mL of tetrahydrofuran was added. The cold bath was subsequently removed, and the reaction mixture stirred for 18 hours. The mixture was concentrated, and the concentrate was treated with 100 mL of dilute (10%) aqueous hydrochloric acid. The resulting suspension was extracted with ether (2*150 mL), and the combined organic extractions were dried (MgSO4) and concentrated in vacuo to give an orange solid. The solid was triturated with boiling dichloromethane, cooled to ambient temperature, and collected by filtration. The solid was rinsed with dichloromethane, and dried in the vacuum-oven (80 C.) to afford 1.39 g (76%) of a yellow-green powder; mp 259.5-262 C.; 1H NMR (400 MD, DMSO): delta9.03 (s, 1H), 7.99 (dd, 1H, J=7.5, 1.9 Hz), 7.57 (dd, 1H, J=1.5 Hz), 7.42 (dd, 1H, J=8.4, 1.9 Hz), 6.70 (dd, 1H, J=8.4, 6.0 Hz), 2.24 (s, 3H); 19F NMR (376 MHz, DMSO): delta-123.40 to -123.47 (m); -139.00 to -139.14 (m); IR (KBr) 1667 (C=O stretch)cm-1; MS (CI) M+1=469. Anal. Calcd/found for C14H9BrF2INO2: C, 35.93/36.15; H. 1.94/1.91; N, 2.99/2.70; Br, 17.07/16.40; F, 8.12/8.46; I, 27.11/26.05.
	With hydrogenchloride; lithium diisopropyl amide; In tetrahydrofuran; n-heptane;	(b) Preparation of 5-Bromo-3,4-difluoro-2-(4-iodo-2-methyl-phenylamino)-benzoic acid To a stirred solution comprised of 1.88 g (0.00791 mol) of 2-amino-5-iodotoluene in 10 mL of tetrahydrofuran at -78 C. was added 6 mL (0.012 mol) of a 2.0 M lithium diisopropylamide in tetrahydrofuran/heptane/ethylbenzene (Aldrich) solution. The resulting green suspension was stirred vigorously for 10 minutes, after which time a solution of 1.00 g (0.00392 mol) of 5-bromo-2,3,4-trifluorobenzoic acid in 15 mL of tetrahydrofuran was added. The cold bath was subsequently removed, and the reaction mixture stirred for 18 hours. The mixture was concentrated, and the concentrate was treated with 100 mL of dilute (10%) aqueous hydrochloric acid. The resulting suspension was extracted with ether (2*150 mL), and the combined organic extractions were dried (MgSO4) and concentrated in vacuo to give an orange solid. The solid was triturated with boiling dichloromethane, cooled to ambient temperature, and collected by filtration. The solid was rinsed with dichloromethane, and dried in the vacuum-oven (80 C.) to afford 1.39 g (76%) of a yellow-green powder; mp 259.5-262 C.; 1H NMR (400 MHz, DMSO): delta 9.03 (s, 1H), 7.99 (dd, 1H, J=7.5, 1.9 Hz), 7.57 (dd, 1H, J=1.5 Hz), 7.42 (dd, 1H, J=8.4, 1.9 Hz), 6.70 (dd, 1H, J=8.4, 6.0 Hz), 2.24 (s, 3H); 19F NMR (376 MHz, DMSO): delta-123.40 to -123.47 (m); -139.00 to -139.14 (m); IR (KBr) 1667 (C=O stretch) cm-1; MS (CI) M+1=469. Analysis calculated for C14H9BrF2INO2: C, 35.93; H, 1.94; N, 2.99; Br, 17.07; F, 8.12; I, 27.11. Found: C, 36.15; H, 1.91; N, 2.70; Br, 16.40; F, 8.46; I, 26.05.

Reference： [1]Synthetic Communications,2002,vol. 32,p. 411 - 417
[2]Patent: US2003/78428,2003,A1
[3]Patent: US6251943,2001,B1
[4]Patent: US6696440,2004,B1
[5]Patent: US2004/54172,2004,A1
[6]Patent: US2004/171632,2004,A1
[7]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 6501 - 6504

8
[ 13194-68-8 ]
1-azido-4-iodo-2-methyl-benzene [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2002,vol. 67,p. 932 - 934

9
[ 13194-68-8 ]
[ 536-74-3 ]
2-methyl-4-{4-phenyl-[1,2,3]triazol-1-yl}phenylamine [ No CAS ]

Reference： [1]Synlett,2005,p. 2941 - 2947

10
[ 13194-68-8 ]
[ 100-39-0 ]
4-benzylsulfanyl-2-methyl-phenylamine [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2006,vol. 71,p. 5781 - 5784

11
[ 13194-68-8 ]
[ 78881-21-7 ]

Yield	Reaction Conditions	Operation in experiment
69.34%	With pyridine; at 150 - 160℃; for 12h;	<strong>[13194-68-8]4-iodo-2-methylaniline</strong> (2000mg, 8.58mmol) and cyanide(1.15g, 12.87mmol, 1.5eq)were added to pyridine. A reaction mixture was heated to 150~160 C and stirred for 12hrs. A reaction mixture was diluted with methylene chloride. A diluted solution was washed with copper sulfate for several times. A mixture was washed with H2O (2 times) and brine, and then dried over Na2SO4. A residue was purified with column chromatography (n-Hexane : EtOAc =2 : 1) to yield a solid (786.5mg, 69.34%). Mp: 78-80 C; IR(NaCl neat, cm-1): 3403, 3335, 3220, 2942, 2220; 1H NMR(400MHz, CDCl3): 7.24(m, 2H), 6.57(d, 1 H, J=8.4Hz), 4.03(bs, 2H), 2.08(s, 9H).

Reference： [1]Patent: EP1862454,2007,A1 .Location in patent: Page/Page column 17

12
[ 13194-68-8 ]
[ 55919-82-9 ]

Yield	Reaction Conditions	Operation in experiment
99%	With acetic acid; sodium nitrite; In water; for 6h;	A solution of 4-iodo-2-methylaniline (10.0 g, 42.9 mmol) in glacial acetic acid (400 mL) was treated with a solution of NaNO2 (2.96 g, 42.9 mmol) in water (10 mL). After stirring for 6 hours, the mixture was concentrated to dryness and dissolved in ethyl acetate (EtOAc). Filtration through a pad of silica gel (EtOAc) provided the title compound (10.4 g, 99%) as a deep purple solid: ESI MS m/z 245 [M+H]+.
	With acetic acid; sodium nitrite; In water; at 10 - 20℃; for 6h;	Example 14; Preparation of 1-(Tetrahydro-2H-pyran-2-yl)-5-(3,3,3-trifluoroprop-1-yn-1-yl)-1H-indazole (Intermediate 28)Step 1: 5-Iodo-1H-indazole To a solution of 4-iodo-2-methylaniline (1.09 g, 4.68 mmol) in CH3CO2H (40 mL), were added NaNO2 (0.39 g, 5.65 mmol) and water (1 mL) at 10 C. The resulting mixture was stirred at room temperature for 6 hours. Upon completion, the reaction mixture was extracted with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel (0-40% EtOAc in petroleum ether) affording the title compound (0.90 g). 1H NMR (DMSO-d6, 400 MHz): delta 13.23 (br, 1H), 8.18 (s, 1H), 8.02 (s, 1H), 7.57 (d, 1H), 7.41 (d, 1H).

Reference： [1]Patent: US2009/82359,2009,A1 .Location in patent: Page/Page column 47
[2]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 3177 - 3180
[3]Patent: US2012/71535,2012,A1 .Location in patent: Page/Page column 53-54
[4]Patent: WO2008/154241,2008,A1

13
[ 611-05-2 ]
[ 13194-68-8 ]

Reference： [1]Monatshefte fur Chemie,1905,vol. 26,p. 1103

14
4,5,6-trifluoro-isophthalic acid [ No CAS ]
[ 13194-68-8 ]
4,5-difluoro-6-(4-iodo-2-methyl-phenylamino)-isophthalic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With LiHMDS; In tetrahydrofuran; at -78 - 20℃; for 4.5h;	A suspension of 4,5,6-trifluoro-isophthalic acid (1.03 g, 4.68 mmol) in freshly distilled THF (20 mL) at -78 C under nitrogen is treated with 2.0 equivalents of freshly prepared 1 M LiHMDS solution (HMDS, 2.07 mL, 9.83 mmol; n-butyllithium, 3.5 mL, 9.36 mmol) in THF. In a second flask is suspended <strong>[13194-68-8]4-iodo-2-methylaniline</strong> (1.09 g, 4.68 mmol) in 20 mL of freshly distilled THF, cooled to -78 C. under nitrogen and treated with 2.0 equiv. of freshly prepared 1M LiHMDS solution (HMDS, 2.07 mL, 9.83 mmol; n-butyllithium, 3.5 mL, 9.36 mmol) in THF. After both solutions stirred for 30 minutes at -78 C., the benzoic acid solution was cannula transferred into the aniline solution and allowed to slowly warm to room temperature. After stirring for 4 hours, the reaction mixture was poured into 200 mL of a saturated HCl diethyl ether solution affording a white precipitate. The solid is filtered off and the remaining filtrate is collected and concentrated in vacuo affording 4,5-fluoro-6-(4-iodo-2-methyl-phenylamino)-isophthalic acid (1.55 g, 77%).

Reference： [1]Patent: US2003/225076,2003,A1 .Location in patent: Page 14

15
[ 866639-18-1 ]
[ 13194-68-8 ]
[ 474557-91-0 ]

Yield	Reaction Conditions	Operation in experiment
84%	In acetonitrile; for 0.166667h;	In 10 ml of acetonitrile was dissolved 1.5 g (4 mmol) of N-(1,1-dimethyl-2-methylthioethyl)-3-iodophthalisoimide, and 0.89 g (3.8 mmol) of <strong>[13194-68-8]4-iodo-2-methylaniline</strong> was added to the solution. After 10 minutes, the crystals precipitated were collected by filtration to obtain 1.94 g of the desired compound. Physical property: m.p. 155-157C. Yield: 84%.

Reference： [1]Patent: EP1389613,2004,A1 .Location in patent: Page 10

16
[ 24424-99-5 ]
[ 13194-68-8 ]
[ 666746-27-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	In toluene; at 80℃; for 16h;	To a mixture of 4-iodo-2-methyl-phenylamine (1.29 g, 5.5 mmol) in toluene (40 mL) was added B0C2O (1.81 g, 8.3 mmol). The resulting mixture was then heated at 80C for 16 h. The solvent was removed in vacuum and the residue was purified by silica gel column chromatography (PE to PE/EA = 20/1) to give (4-iodo-2-methyl-phenyl)-carbamic acid tert- butyl ester (1.8 g, 99% yield) as white solid. NMR (300 MHz, CDCh): d = 7.64 (d, J= 9.7 Hz, 1H), 7.55 - 7.41 (m, 2H), 6.24 (brs, 1H), 2.21 (s, 3H), 1.53 (s, 9H). MS: m/z 334.0 (M+H+ ).
	In toluene; for 2h;Heating / reflux;	Step 1; Preparation of t-butyl 4-iodo-2-methylcarbanilate. To 30 ml of a toluene solution containing 10.0 g of 4-iodo-2-methylaniline was added 14.0 g of di-t-butyl dicarbonate, and the mixture was stirred under reflux for 2 hours. After completion of the reaction, 30 ml of water was added to the mixture and the resulting mixture was refluxed for 15 minutes, cooled to room temperature by allowing to stand, and extracted by 100 ml of diethyl ether. The organic layer was washed with water, dried over anhydrous magnesium sulfate, the solvent was removed under reduced pressure, and the residual solid was washed with hexane to obtain 11.5 g of the objective material as white crystals. Melting point 101.0 to 103.0C1H NMR (CDCl3, Me4Si, 300MHz) δ 7.63 (d, J=8.4Hz, 1 H), 7.45-7.5 (m, 2H), 6.22 (bs, 1 H), 2.19 (s, 3H), 1.52 (s, 9H). Step 2; Preparation of t-butyl 2-methyl-4-(1-trifluoromethylethenyl)carbanilate.

Reference： [1]Patent: WO2021/50547,2021,A1 .Location in patent: Paragraph 0103-0105; 0142-0144; 0151-0153
[2]Patent: EP1538138,2005,A1 .Location in patent: Page/Page column 499

17
[ 871681-64-0 ]
[ 13194-68-8 ]
[ 871681-81-1 ]

Yield	Reaction Conditions	Operation in experiment
13%	With sodium t-butanolate; In 1,4-dioxane; at 80℃; for 1.5h;Microwave irradiation;	A mixture of 4-(6-chloro-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester (687 mg, 2.29 mmol), <strong>[13194-68-8]2-methyl-4-iodoaniline</strong> ( 533 mg, 2.29 mmol), and sodium tert-butoxide (220 mg, 2.29 mmol) in 20 mL dioxane were- heated under microwave irradiation for 90 minutes at 80C.- -- Mixture was purified by HPLC to give 4-[6-(4-iodo-2-methyl-phenylamino)-pyrimidin-4-yloxy]- piperidine-1-carboxylic acid isopropyl ester as a white solid (TFA salt, 188 mg, 13%). ¹HNMR (MeOD, 400 MHz) No. 1.01-1.03 (d, 6H), 1.45-1.52 (m, 2H), 1.73-1.80 (m, 2H), 1.99 (s, 3H), 3.10-3.18 (m, 2H), 3.47-3.53 (m, 1H), 4.94-4.97 (m, 1H), 5.70 (s, 1H), 6.88-6.90 (d, 1H), 7.37-7.39 (d, 1H), 7.49 (s, 1H), 8.06 (s, 1H). Exact mass calculated for C2oH25IN403 496.10, found 496.34 (MH+).

Reference： [1]Patent: WO2005/121121,2005,A2 .Location in patent: Page/Page column 169

18
[ 40296-46-6 ]
[ 13194-68-8 ]
[ 888482-62-0 ]

Yield	Reaction Conditions	Operation in experiment
20%		Ethyl 4,6-dichloronicotinate (1) (3.2g, 14.5mmol) and <strong>[13194-68-8]4-iodo-2-methylaniline</strong> (3.Og, 13.6mmol) are dissolved in dry THF (15ml) under argon and the mixture is cooled to - 780C. A solution of LiHMDS (1.0M in THF, 48ml) is slowly added and the reaction mixture is allowed to warm to ambient temperature. After 18h the reaction is quenched by adding dilute hydrochloric acid (1.0M, 30.0ml) and the mixture is extracted with DCM (3x 80ml). The combined organic extracts are concentrated in vacuo and the crude material is purified by flash chromatography using silica gel and a gradient of 0-20% ethylacetate in cyclohexane as eluent to give pure 4-(4-iodo-2-methyl-phenylamino)-6-chloro-nicotinic acid ethyl ester (2b) (1.2g, 20% yield).
12%	With lithium hexamethyldisilazane; In tetrahydrofuran; at -78 - 20℃; for 20h;	Step A; Ethyl 4,6-dichloronicotinate (1) (3.Og, 14mmol) and <strong>[13194-68-8]4-iodo-2-methylaniline</strong> (3.2g, 14mmol) are dissolved in dry THF (20ml) under argon and the mixture is cooled to -78C. A solution of LiHMDS (1.0M in THF, 48ml) is slowly added and the reaction mixture is allowed to warm to ambient temperature. The reaction is quenched after 2Oh by adding dilute hydrochloric acid (1.0M, 20.0ml), the volatiles are evaporated and the residue is extracted with DCM (3x 60ml). The combined organic extracts are concentrated in vacuo and the crude material is purified EPO <DP n="33"/>by flash chromatography using silica gel and a gradient of 0-10% ethylacetate in cyclohexane as eluent to give pure ethyl 4-[(4-iodo-2-methylphenyl)amino]-6-chloronicotinate (700mg, 12% yield).LC-MS method (VIII) rt 5.64 min; m/z 417 [M+H]+, Cl pattern. 1H-NMR (400MHz, DMSO-d6): delta = 1.33 (t, J = 7.1Hz, 3H), 2.13 (s, 3H), 4.35 (q, J = 7.1 Hz, 2H), 6.41 (s, 1 H), 7.12 (d, J = 8.6Hz, 1 H), 7.63 (d, J = 8.1 Hz, 1 H), 7.76 (s, 1 H), 8.65 (s, 1 H), 9.52 (b, 1 H).

Reference： [1]Patent: WO2006/56427,2006,A1 .Location in patent: Page/Page column 47
[2]Patent: WO2006/58752,2006,A1 .Location in patent: Page/Page column 31-32

19
[ 13194-68-8 ]
[ 1583-58-0 ]
[ 212628-43-8 ]

Yield	Reaction Conditions	Operation in experiment
1.10 g (47%)	With hydrogenchloride; Hg; lithium diisopropyl amide; In tetrahydrofuran; n-heptane;	(a) Preparation of 4-Fluoro-2-(4-iodo-2-methyl-phenylamino)-benzoic acid To a stirred solution containing 3.16 g (0.0133 mol) of 2-amino-5-iodotoluene in 5 mL of tetrahydrofuran at -78 C. was added 10 mL (0.020 mol) of a 2.0 M lithium diisopropylamide in tetrahydrofuran/heptane/ethylbenzene (Aldrich) solution. The resulting green suspension was stirred vigorously for 15 minutes, after which time a solution of 1.00 g (0.00632 mol) of 2,4-difluorobenzoic acid in 10 mL of tetrahydrofuran was added. The reaction 2,4-difluorobenzoic acid in 10 mL of tetrahydrofuran was added. The reaction temperature was allowed to increase slowly to room temperature, at which temperature the mixture was stirred for 2 days. The reaction mixture was concentrated by evaporation of the solvent under reduced pressure. Aqueous HCl (10%) was added to the concentrate, and the solution was extracted with dichloromethane. The organic phase was dried (MgSO4) and then concentrated over a steambath to low volume (10 mL) and cooled to room temperature. The off-white fibers which formed were collected by vacuum filtration, rinsed with hexane, and dried in a vacuum-oven (76 C.; ca. 10 mm of Hg) to afford 1.10 g (47%) of the desired material; mp 224-229.5 C.; 1H NMR (400 MHz, DMSO): delta9.72 (s, 1H), 7.97 (dd, 1H, J=7.0, 8.7 Hz), 7.70 (d, 1H, J=1.5 Hz), 7.57 (dd, 1H, J=8.4, 1.9 Hz), 7.17 (d, 1H, J=8.2 Hz), 6.61-6.53 (m, 2H), 2.18 (s, 3H); 13C NMR (100 MHz, DMSO): delta169.87, 166.36 (d, JC-F=249.4 Hz), 150.11 (d, JC-F=11.4 Hz), 139.83, 138.49, 136.07, 135.26 (d, JC-F=11.5 Hz), 135.07, 125.60, 109.32, 104.98 (d, JC-F=21.1 Hz), 99.54 (d, JC-F=26.0 Hz), 89.43, 17.52; 19F NMR (376 MHz, DMSO): delta-104.00 to -104.07 (m); IR (KBr) 1670 (C=O stretch)cm-1; MS (CI) M+1=372. Analysis calculated for C14H11FINO2: C, 45.31; H, 2.99; N, 3.77. Found: C, 45.21; H, 2.77; N, 3.64.
1.10 g (47%)	With hydrogenchloride; Hg; lithium diisopropyl amide; In tetrahydrofuran; n-heptane;	EXAMPLE 1 4-Fluoro-2-(4-iodo-2-methylphenylamino)benzoic acid To a stirring solution comprised of 3.16 g (0.0133 mol) of 2-amino-5-iodotoluene in 5 mL of tetrahydrofuran at -78 C. was added 10 mL (0.020 mol) of a 2.0 M lithium diisopropylamide in tetrahydrofuran/heptane/ethenylbenzene (Aldrich) solution. The resulting green suspension was stirred vigorously for 15 minutes, after which time a solution of 1.00 g (0.00632 mol) of 2,4-difluorobenzoic acid in 10 mL of tetrahydrofuran was added. The reaction temperature was allowed to increase slowly to room temperature, at which temperature it was stirred for 2 days. The reaction mixture was concentrated. Aqueous HCl (10%) was added to the concentrate, and the solution was extracted with dichloromethane. The organic phase was dried (MgSO4) and then boiled over a steambath to low volume and cooled to room temperature. The off-white fibers were collected by vacuum filtration, rinsed with hexanes, and vacuum-oven dried. (76 C.; ca. 10 mm of Hg) to afford 1.10 g (47%) of the desired material; mp 224-229.5 C.; 1H NMR (400 MHz; DMSO): Lambda 9.72 (s, 1H), 7.97 (dd, 1H, J=7.0, 8.7 Hz), 7.70 (d, 1H, J=1.5 Hz), 7.57 (dd, 1H, J=8.4, 1.9 Hz), 7.17 (d, 1H, J=8.2 Hz), 6.61-6.53 (m, 2H), 2.18 (s, 3H); 13C NMR (100 MHz; DMSO): Lambda 169.87, 167.60, 165.12, 150.17, 150.05, 139.83, 138.49, 136.07, 135.31, 135.20, 135.07, 125.60, 109.32, 105.09, 104.87, 99.72, 99.46, 89.43, 17.52; 19F NMR (376 MHz; DMSO): delta-104.00 to -104.07 (m); IR (KBr) 1670 (C=O stretch) cm-1; MS (CI) M+1=372. Analysis calculated for C14H11FINO2: C, 45.31; H, 2.99; N, 3.77. Found: C, 45.21; H, 2.77; N, 3.64.
1.10 g (47%)	With Hg; lithium diisopropyl amide; In tetrahydrofuran; n-heptane;	(a) Preparation of 4Fluoro-2-(4iodo-2-methyl-phenylamino)-benzoic acid To a stirred solution containing 3.16 g (0.0133 mol) of 2-amino-5-iodotoluene in 5 mL of tetrahydrofuran at -78 C. was added 10 mL (0.020 mol) of a 2.0 M lithium diisopropylamide in tetrahydrofuran/heptane/ethylbenzene (Aldrich) solution. The resulting green suspension was stirred vigorously for 15 minutes, after which time a solution of 1.00 g (0.00632 mol) of 2,4-difluorobenzoic acid in 10 mL of tetrahydrofuran was added. The reaction temperature was allowed to increase slowly to room temperature, at which temperature the mixture was stirred for 2 days. The reaction mixture was concentrated by evaporation of the solvent under reduced pressure. Aqueous HCI (10%) was added to the concentrate, and the solution was extracted with dichloromethane. The organic phase was dried (MgSO4) and then concentrated over a steambath to low volume (10 mL) and cooled to room temperature. The off-white fibers which formed were collected by vacuum filtration, rinsed with hexane, and dried in a vacuum-oven (76 C.; ca. 10 mm of Hg) to afford 1.10 g (47%) of the desired material; mp 224-229.5 C.; 1H NMR (400 MHz, DMSO): delta 9.72 (s, 1H), 7.97 (dd, 1H, J=7.0, 8.7 Hz), 7.70 (d, 1H, J=1.5 Hz), 7.57 (dd, 1H,.J=8.4, 1.9 Hz), 7.17 (d, 1H, J=8.2 Hz), 6.61-6.53 (m, 2H), 2.18 (s, 3H); 13C NMR (100 MHz, DMSO): delta 169.87, 166.36 (d, JC-F=249.4 Hz), 150.11 (d, JC-F=11.4 Hz), 139.83, 138.49, 136.07, 135.26 (d, JC-F=11.5 Hz), 135.07, 125.60, 109.32, 104.98 (d, JC-F=21.1 Hz), 99.54 (d, JC-F=26.0 Hz), 89.43, 17.52; 19F NMR (376 MHz, DMSO): delta104.00 to -104.07 (m); IR (KBr) 1670 (C=O stretch)cm-1; MS (CI) M+1=372.

1.10 g (47%)	With hydrogenchloride; Hg; lithium diisopropyl amide; In tetrahydrofuran; n-heptane;	EXAMPLE 1 4-Fluoro-2-(4-iodo-2-methylphenylamino)benzoic Acid To a stirring solution comprised of 3.16 g (0.0133 mol) of 2-amino-5-iodotoluene in 5 mL of tetrahydrofuran at -78 C. was added 10 mL (0.020 mol) of a 2.0 M lithium diisopropylamide in tetrahydrofuran/heptane/ethenylbenzene (Aldrich) solution. The resulting green suspension was stirred vigorously for 15 minutes, after which time a solution of 1.00 g (0.00632 mol) of 2,4-difluorobenzoic acid in 10 mL of tetrahydrofuran was added. The reaction temperature was allowed to increase slowly to room temperature, at which temperature it was stirred for 2 days. The reaction mixture was concentrated. Aqueous HCl (10%) was added to the concentrate, and the solution was extracted with dichloromethane. The organic phase was dried (MgSO4) and then boiled over a steambath to low volume and cooled to room temperature. The off-white fibers were collected by vacuum filtration, rinsed with hexanes, and vacuum-oven dried. (76 C.; ca. 10 mm of Hg) to afford 1.10 g (47%) of the desired material; mp 224-229.5 C.; 1H NMR (400 MHz; DMSO): delta 9.72 (s, 1H), 7.97 (dd, 1H, J=7.0, 8.7 Hz), 7.70 (d, 1H, J=1.5 Hz), 7.57 (dd, 1H, J=8.4, 1.9 Hz), 7.17 (d, 1H, J=8.2 Hz), 6.61-6.53 (m, 2H), 2.18 (s, 3H); 13C NMR (100 MHz; DMSO): delta 69.87, 167.60, 165.12, 150.17, 150.05, 139.83, 138.49, 136.07, 135.31, 135.20, 135.07, 125.60, 109.32, 105.09, 104.87, 99.72, 99.46, 89.43, 17.52; 19F NMR (376 MHz; DMSO): delta -104.00 to -104.07 (m); IR (KBr) 1670 (C=O stretch) cm-1; MS (CI) M+1=372. Analysis calculated for C14H11FINO2: C, 45.31; H, 2.99; N, 3.77. Found: C, 45.21; H, 2.77; N, 3.64.
1.10 g (47%)	With hydrogenchloride; Hg; lithium diisopropyl amide; In tetrahydrofuran; n-heptane;	(a) Preparation of 4-Fluoro-2-(4-iodo-2-methyl-phenylamino)-benzoic Acid To a stirred solution containing 3.16 g (0.0133 mol) of 2-amino-5-iodotoluene in 5 mL of tetrahydrofuran at -78 C. was added 10 mL (0.020 mol) of a 2.0 M lithium diisopropylamide in tetrahydrofuran/heptane/ethylbenzene (Aldrich) solution. The resulting green suspension was stirred vigorously for 15 minutes, after which time a solution of 1.00 g (0.00632 mol) of 2,4-difluorobenzoic acid in 10 mL of tetrahydrofuran was added. The reaction temperature was allowed to increase slowly to room temperature, at which temperature the mixture was stirred for 2 days. The reaction mixture was concentrated by evaporation of the solvent under reduced pressure. Aqueous HCl (10%) was added to the concentrate, and the solution was extracted with dichloromethane. The organic phase was dried (MgSO4) and then concentrated over a steambath to low volume (10 mL) and cooled to room temperature. The off-white fibers which formed were collected by vacuum filtration, rinsed with hexane, and dried in a vacuum-oven (76 C.; ca. 10 mm of Hg) to afford 1.10 g (47%) of the desired material; mp 224-229.5 C.; 1H NMR (400 MHz, DMSO): delta 9.72 (s, 1H), 7.97 (dd, 1H, J=7.0, 8.7 Hz), 7.70 (d, 1H, J=1.5 Hz), 7.57 (dd, 1H, J=8.4, 1.9 Hz), 7.17 (d, 1H, J=8.2 Hz), 6.61-6.53 (m, 2H), 2.18 (s, 3H); 13C NMR (100 MHz, DMSO): delta 169.87, 166.36 (d, JC-F=249.4 Hz), 150.11 (d, JC-F=11.4 Hz), 139.83, 138.49, 136.07, 135.26 (d, JC-F=1.5 Hz), 135.07, 125.60, 109.32, 104.98 (d, JC-F=21.1 Hz), 99.54 (d, JC-F=26.0 Hz), 89.43, 17.52; 19F NMR (376 MHz, DMSO): delta -104.00 to -104.07 (m); IR (KBr) 1670 (C=O stretch)cm-1; MS (CI) M+1 372. Analysis calculated for C14H11FINO2: C, 45.31; H, 2.99; N, 3.77. Found: C, 45.21; H, 2.77; N, 3.64.
1.10 g (47%)	With hydrogenchloride; Hg; lithium diisopropyl amide; In tetrahydrofuran; n-heptane;	EXAMPLE 1 4-Fluoro-2-(4-iodo-2-methylphenylamino)benzoic acid To a stirring solution comprised of 3.16 g (0.0133 mol) of 2-amino-5-iodotoluene in 5 mL of tetrahydrofuran at -78 C. was added 10 mL (0.020 mol) of a 2.0 M lithium diisopropylamide in tetrahydrofuran/heptane/ethenylbenzene (Aldrich) solution. The resulting green suspension was stirred vigorously for 15 minutes, after which time a solution of 1.00 g (0.00632 mol) of 2,4-difluorobenzoic acid in 10 mL of tetrahydrofuran was added. The reaction temperature was allowed to increase slowly to room temperature, at which temperature it was stirred for 2 days. The reaction mixture was concentrated. Aqueous HCl (10%) was added to the concentrate, and the solution was extracted with dichloromethane. The organic phase was dried (MgSO4) and then boiled over a steambath to low volume and cooled to room temperature. The off-white fibers were collected by vacuum filtration, rinsed with hexanes, and vacuum-oven dried. (76 C.; ca. 10 mm of Hg) to afford 1.10 g (47%) of the desired material; mp 224-229.5 C.; 1H NMR (400 MHz; DMSO): delta 9.72 (s, 1H), 7.97 (dd, 1H, J=7.0, 8.7 Hz), 7.70 (d, 1H, J=1.5 Hz), 7.57 (dd, 1H, J=8.4, 1.9 Hz), 7.17 (d, 1H, J=8.2 Hz), 6.61-6.53 (m, 2H), 2.18 (s, 3H); 13C NMR (100 MHz; DMSO): delta 169.87, 167.60, 165.12, 150.17, 150.05, 139.83, 138.49, 136.07, 135.31, 135.20, 135.07, 125.60, 109.32, 105.09, 104.87, 99.72, 99.46, 89.43, 17.52; 19F NMR (376 MHz; DMSO): delta-104.00 to -104.07 (m); IR (KBr) 1670 (C=0 stretch) cm-1; MS (CI) M+1=372. Analysis calculated for C14H11FINO2: C, 45.31; H, 2.99; N, 3.77. Found: C, 45.21; H, 2.77; N, 3.64.
1.10 g (47%)	With hydrogenchloride; Hg; lithium diisopropyl amide; In tetrahydrofuran; n-heptane;	(a) Preparation of 4-Fluoro-2-(4-iodo-2-methyl-phenylamino)-benzoic acid To a stirred solution containing 3.16 g (0.0133 mol) of 2-amino-5-iodotoluene in 5 mL of tetrahydrofuran at -78 C. was added 10 mL (0.020 mol) of a 2.0 M lithium diisopropylamide in tetrahydrofuran/heptane/ethylbenzene (Aldrich) solution. The resulting green suspension was stirred vigorously for 15 minutes, after which time a solution of 1.00 g (0.00632 mol) of 2,4-difluorobenzoic acid in 10 mL of tetrahydrofuran was added. The reaction temperature was allowed to increase slowly to room temperature, at which temperature the mixture was stirred for 2 days. The reaction mixture was concentrated by evaporation of the solvent under reduced pressure. Aqueous HCl (10%) was added to the concentrate, and the solution was extracted with dichloromethane. The organic phase was dried (MgSO4) and then concentrated over a steambath to low volume (10 mL) and cooled to room temperature. The off-white fibers which formed were collected by vacuum filtration, rinsed with hexane, and dried in a vacuum-oven (76 C.; ca. 10 mm of Hg) to afford 1.10 g (47%) of the desired material; mp 224-229.5 C.; 1H NMR (400 MHz, DMSO): delta 9.72 (s, 1H), 7.97 (dd, 1H, J=7.0, 8.7 Hz), 7.70 (d, 1H, J=1.5 Hz), 7.57 (dd, 1H, J=8.4, 1.9 Hz), 7.17 (d, 1H, J=8.2 Hz), 6.61-6.53 (m, 2H), 2.18 (s, 3H); 13C NMR (100 MHz, DMSO): delta 169.87, 166.36 (d,JC-F=249.4 Hz), 150.11 (d, JC-F=11.4 Hz), 139.83, 138.49, 136.07, 135.26 (d,JC-F=11.5 Hz), 135.07, 125.60, 109.32, 104.98 (d, JC-F=21.1 Hz), 99.54 (d, JC-F=26.0 Hz), 89.43, 17.52; 19F NMR (376 MHz, DMSO): delta-104.00 to -104.07 (m); IR (KBr) 1670 (C=O stretch)cm-1; MS (CI) M+1=372. Analysis calculated for C14H11FINO2: C, 45.31; H, 2.99; N, 3.77. Found: C, 45.21; H, 2.77; N, 3.64.

Reference： [1]Patent: US2003/78428,2003,A1
[2]Patent: US6310060,2001,B1
[3]Patent: US6251943,2001,B1
[4]Patent: US6696440,2004,B1
[5]Patent: US6696440,2004,B1
[6]Patent: US2004/171632,2004,A1
[7]Patent: US2004/171632,2004,A1
[8]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 6501 - 6504

20
[ 13194-68-8 ]
[ 544-92-3 ]
[ 78881-21-7 ]

Yield	Reaction Conditions	Operation in experiment
69.34%	With pyridine; at 150 - 160℃; for 12h;	Example 8: N-{4-[3-(4-tert-Butyl-benzyl)-ureidomethyl]-2-methyl-6-vinyl-phenyl}-methanesulfonamide; EPO <DP n="91"/>Step 1 : 4-Amino-3-methylbenzonitrile; <strong>[13194-68-8]4-iodo-2-methylaniline</strong> (2000mg, 8.58mmol) and cyanide(1.15g, 12.87mmol, 1.5eq)were added pyridine. A reaction mixture was heated to 150~160C , stirred for 12hr. A reaction mixture was diluted with methylene chloride. A diluted solution was washed with copper sulfate for several times. A mixture was washed with H2O (2 times) and b.rine, and then dried with Na2SO4. A residue was purified with column chromatography (n-Hexane: EtOAc =2 : 1 ) to yield solid (786.5mg, 69.34%).mp: 78-80 C ;IR(NaCI neat, cm"1) : 3403, 3335, 3220, 2942, 2220;1H NMR(400MHz, CDCI3): 7.24(m, 2H), 6.57(d, 1H, J=8.4Hz), 4.03(bs, 2H), 2.08(s, 9H).

Reference： [1]Patent: WO2006/101318,2006,A1 .Location in patent: Page/Page column 90

21
[ 13194-68-8 ]
[ 536-74-3 ]
[ 877603-43-5 ]

Yield	Reaction Conditions	Operation in experiment
	With N-butylamine;copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); In diethyl ether; for 6h;	<strong>[13194-68-8]4-iodo-2-methylbenzenamine</strong> (24, 233mg, 1 mmol) on reaction with ethynyl benzene (25a, 102 mg, lmmol) by employing Sonagashira coupling conditions using Pd(PPh3)4 (69.3 mg, 0.06 equiv) as catalyst, Cul (22.8 mg, 0.12equiv) as cocatalyst, butyl amine (261 mg, 3 equiv) as base and ether as solvent and kept the reaction for 6h. After completion of the reaction as indicated by TLC and the reaction mixture is extracted into ether (4x25 mL) from the aqueous layer and concentrated in vacuo. The compound was further purified by column chromatography using 60-120 silica gel (ethyl acetate/hexane,l:9) to obtain 2-methyl-4-(phenylethynyl)benzenamine compound (26a) as pure product. Anthranilic acid (27, 137 mg, lmmol) on reaction with acetic anhydride at 150 C and reflux for 30 min, after completion of reaction aqueous sodium bicarbonate solution is added and extracted in ethyl acetate (4x25 mL) from the aqueous layer and concentrated in vacuo afforded 2-methyl 4H- benzo [of][l,3] oxazin-4-one compound (28) as pure product. To a stirred solution of 2-methyl-4- (phenylethynyl)benzenamine (26a, 207 mg, lmmol) with 2-methyl-4H-benzo [d][l,3]oxazin-4-one (28, 161 mg, lmmol) in acetic acid and reflux for 8h. After completion of the reaction as indicated by TLC. The reaction mixture was quenched with NaHC03 and extracted in ethyl acetate (4x25 mL) from the ice cold aqueous layer and dried over anhydrous Na2S04 afforded 2-methyl-3-(2-methyl-4- (phenylethynyl) phenyl)quinazolin-4(3W)-one (29a). Reaction of 2-methyl-3-(2-methyl-4-(phenyl ethynyl)phenyl)quinazolin-4(3H)-one (29a, 350 mg, lmmol) with 4-hydroxy benzaldehyde (30b, 122 mg, lmmol) was taken in acetic acid Then the resulting mixture was stirred under reflux conditions for 8 h and then the reaction mixture was quenched with NaHC03 and extracted in ethyl acetate (4x25 mL) from the ice cold aqueous layer and dried over anhydrous Na2S04.The resulting product (4b) was purified by column chromatography employing EtOAc/Hexane as an eluent.p 161-162 0 C; H NMR (CDCI3+DMSO-d6, 200 MHz) delta 8.29 (s, 1H), 8.27 (d, J = 15.1 Hz, 1H), 7.77 (d, J = 3.6 Hz, 2H), 7.57 (d, J = 9.4, 1H), 7.52 (dd, J = 3.9, 7.5 Hz, 2H), 7.46 (t, J = 3.9 Hz, lH), 7.40-7.27 ( m, 3H), 7.26-7.06 (m, 6H), 6.25 (d, J = 15.3 Hz, 1H), 2.16 (s, 3H); LRMS(ESI, m/z) 455 (M)+ .
	With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); N-butylamine; In diethyl ether; at 25 - 30℃; for 6h;	<strong>[13194-68-8]4-iodo-2-methylbenzenamine</strong> (24, 233 mg, 1 mmol) on reaction with ethynyl benzene (25a, 102 mg, 1 mmol) by employing Sonagashira coupling conditions using Pd(PPh3)4 (69.3 mg, 0.06 equiv) as catalyst, Cul (22.8 mg, 0.12 equiv) as cocatalyst, butyl amine (261 mg, 3 equiv) as base and ether as solvent and kept the reaction for 6 h. After completion of the reaction as indicated by TLC and the reaction mixture is extracted into ether (4×25 mL) from the aqueous layer and concentrated in vacuo. The compound was further purified by column chromatography using 60-120 silica gel (ethyl acetate/hexane,1:9) to obtain 2-methyl-4-(phenylethynyl)benzenamine compound (26a) as pure product. Anthranilic acid (27, 137 mg, 1 mmol) on reaction with acetic anhydride at 150 C. and reflux for 30 min, after completion of reaction aqueous sodium bicarbonate solution is added and extracted in ethyl acetate (4×25 mL) from the aqueous layer and concentrated in vacuo afforded 2-methyl 4H-benzo[d][1,3]oxazin-4-one compound ( 28) as pure product. To a stirred solution of 2-methyl-4-(phenylethynyl)benzenamine (26a, 207 mg, 1 mmol) with 2-methyl-4H-benzo[d][1,3]oxazin-4-one (28, 161 mg, 1 mmol) in acetic acid and reflux for 8 h. After completion of the reaction as indicated by TLC. The reaction mixture was quenched with NaHCO3 and extracted in ethyl acetate (4×25 mL) from the ice cold aqueous layer and dried over anhydrous Na2SO4 afforded 2-methyl-3-(2-methyl-4-(phenylethynyl)phenyl)quinazolin-4(3H)-one (29a). Reaction of 2-methyl-3-(2-methyl-4-(phenylethynyl)phenyl)quinazolin-4(3H)-one ethynyl)phenyl)quinazolin-4(3H)-one (29a, 350 mg, 1 mmol) with 4-hydroxy benzaldehyde (30b, 122 mg, 1 mmol) was taken in acetic acid Then the resulting mixture was stirred under reflux conditions for 8 h and then the reaction mixture was quenched with NaHCO3 and extracted in ethyl acetate (4×25 mL) from the ice cold aqueous layer and dried over anhydrous Na2SO4.The resulting product ( 4b) was purified by column chromatography employing EtOAc/Hexane as an eluent.
	With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine; In N,N-dimethyl-formamide; at 100℃; for 16h;Inert atmosphere;	A mixture of ethynylbenzene (200 mg, 1.96 mmol, 215.05 muL, 1 eq), <strong>[13194-68-8]4-iodo-2-methyl-aniline</strong> (456.36 mg, 1.96 mmol, 1 eq), TEA (594.46 mg, 5.87 mmol, 817.69 muL, 3.0 eq), CuI (74.59 mg, 391.65 mumol, 0.2 eq) and Pd(PPh3)4 (226.29 mg, 195.82 mumol, 0.1 eq) in DMF (10 mL) was degassed and purged with N2 for 3 times, the mixture was stirred at 100 C. for 16 h under N2. The reaction mixture was quenched by addition of water (50 mL), extracted with EtOAc (30 mL*3). The combined organic layers were washed with brine (10 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue which was purified by flash silica gel chromatography (from PE/EtOAc=1/0 to 5/1, TLC: PE/EtOAc=5/1, Rf=0.28) to yield 2-methyl-4-(2-phenylethynyl)aniline (160 mg, 725.62 umol, 37.1% yield, 94.0% purity) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) delta ppm 7.48-7.29 (m, 5H), 7.15-7.04 (m, 2H), 6.60 (d, J=8.2 Hz, 1H), 5.33 (s, 2H), 2.05 (s, 3H); ES-LCMS m/z 208.1 [M+H]+.

Reference： [1]Patent: WO2006/22442,2006,A1 .Location in patent: Page/Page column 57-58
[2]Patent: WO2012/111017,2012,A1 .Location in patent: Page/Page column 19-20
[3]MedChemComm,2013,vol. 4,p. 575 - 581
[4]Patent: US2013/317221,2013,A1 .Location in patent: Paragraph 0141; 0131; 0133; 0126
[5]Patent: US2019/55218,2019,A1 .Location in patent: Paragraph 0351; 0352; 0353

22
[ 13194-68-8 ]
[ 884602-27-1 ]

Yield	Reaction Conditions	Operation in experiment
64%		A cold (O0C) suspension of 5-iodo-2-methylaniline (7.Og, 0.03M) in HCl (5M, 30ml) was treated dropwise with a solution of sodium nitrite (2.28g, 0.033mmol) in water (3ml) over 20 minutes. The solution was stirred for 20 minutes before sodium azide was added portionwise over 15 minutes. The mixture was stirred for 30 minutes then poured into water. The mixture was diluted with DCM and the pH adjusted to 7 by the addition of Na2COa. The phases were separated and the organic layer was dried (MgSO4) and concentrated under vacuum. . The residue was purified by chromatography (silica, 5% Et2O/hexanes followed by 10% EtOAc/Hexanes) to give the azide (5.1g, 64%). 1H NMR (500 MHz, CDCl3): delta 2.14 (3H, s), 6.88 (IH, d, J 7.9), 7.35 (IH, d, J 7.9), 7.39 (IH, d, J 1.3).

Reference： [1]Patent: WO2006/43064,2006,A1 .Location in patent: Page/Page column 103-104

23
[ 463-71-8 ]
[ 13194-68-8 ]
[ 143014-18-0 ]

Yield	Reaction Conditions	Operation in experiment
89%	In dichloromethane; water;	INTERMEDIATE 8; 4-Iodo- 1 -isothiocvanato-2-methylbenzene; To a stirring solution of <strong>[13194-68-8]4-iodo-2-methylaniline</strong> (1.0 g, 4.2 mmol) in DCM (50 niL) was added water (20 mL) followed by thiophosgene (490 mg, 4.2 mmol). The reaction mixture was stirred overnight before the layers were separated and the organic layer dried (Na2SO4) and evaporated in vacuo to give the desired product as a brown solid (1.05 g, 89%). deltaH (CDCl3) 7.75 (IH, d, J 1.2 Hz), 7.62 (IH, dd, J 1.2, 8.3 Hz), 7.15 (IH, d, J8.3 Hz), 2.20 (3H, s).
	With potassium carbonate; In chloroform; water;	Step A 4-Iodo-2-methylphenyl isothiocyanate To a stirred mixture of 9.9 g (0.086 mole) of thiophosgene, 5.0 g (0.036 mole) of potassium carbonate in 55 ml of water and 100 ml of chloroform was added a solution of 20.0 g (0.0862 mole) of <strong>[13194-68-8]4-iodo-2-methylaniline</strong> in 50 ml of chloroform. Additional potassium carbonate was added to make the reaction mixture basic. An additional 9.9 g of thiophosgene was added, and the reaction mixture was stirred at room temperature for approximately 18 hours. The mixture was partitioned between water (100 ml) and chloroform (100 ml). The organic phase was dried over anhydrous magnesium sulfate and was filtered. The filtrate was evaporated under reduced pressure, leaving a residue. This residue was purified by column chromatography on silica gel, eluding with methylene chloride to yield 22.6 g of 4-iodo-2-methylphenyl isothiocyanate as a solid, mp 51-53 C.

Reference： [1]Patent: WO2007/88345,2007,A1 .Location in patent: Page/Page column 22
[2]Patent: US5108486,1992,A
[3]Chemical Communications,2016,vol. 52,p. 8444 - 8447

24
[ 13194-68-8 ]
C₇H₆IN₂⁽¹⁺⁾*Cl^(1-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium nitrite; In water; at 0 - 5℃; for 2.33333h;	To <strong>[13194-68-8]4-iodo-2-methylaniline</strong> (23.3g) (available from Fluorochem) in ice (6Og) and concentrated hydrochloric acid (30ml) was added a solution of sodium nitrite (7.05g) in water (18ml) slowly with stirring over 20min, keeping the temperature below 50C. The mixture was allowed to stand at 0-50C for 2h, then added slowly at 0-50C over 30min to a mixture of diethyl malonate (17ml), ethanol (300ml) and water (50ml) containing sodium acetate (18.8g). The mixture was stirred for 2h at 0-50C then for 2h at 210C. The mixture was concentrated in vacuo to a volume of about 200ml, and the product was collected by filtration, washed with water (200ml) and dried under vacuum to give the title compound as a brown solid (28.9g). LC/MS Rt 3.85min m/z 405 [MH+].

Reference： [1]Patent: WO2007/45861,2007,A1 .Location in patent: Page/Page column 39

25
[ 106-44-5 ]
[ 13194-68-8 ]
[ 1113063-00-5 ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 3; Synthesis of (3); A flask is charged with 100 mmol of boric acid followed by 6N HCl solution to adjust the reaction solution to a pH of 2. Once the salt dissolves, 20 mmol of <strong>[13194-68-8]4-iodo-2-methylaniline</strong> is added to the reaction solution, followed by enough ice to reduce solution temperature to 0 C. In a separate flask, 20 mmol of sodium nitrite (NaNO2) is dissolved in ice water. The NaNO2 solution is added drop-wise with constant stirring to the <strong>[13194-68-8]4-iodo-2-methylaniline</strong> solution. The pH of the reaction solution is maintained by addition of 6N HCl. After the NaNO2 solution addition is complete, ice is added to maintain the 0 C. reaction temperature. A 3rd flask is charged with 20 mmol of p-cresol, water and 2.5 N NaOH (20 mmol), which is then added drop wise to the ice cooled reaction with constant stirring. The reaction mixture is allowed to stir for 15 min at pH 2.0-2.5. NaOH (2.5 N) is then added in small aliquots to the reaction solution to increase the pH to 8.5. The reaction solution is allowed to warm to room temperature. Dibasic sodium phosphate solution (100 mmol) is added and the pH is adjusted to 6.0 with 6 N HCl. The product is filtered, rinsed with ice water and air dried. The product is purified by column chromatography to yield 2-(4-iodo-2-methyl-phenylazo)-4-methyl-phenol (3).

Reference： [1]Patent: US2009/43105,2009,A1 .Location in patent: Page/Page column 2; 4

26
[ 13194-68-8 ]
[ 2991-28-8 ]
5-Fluoro-2-(4-iodo-2-methyl-phenylamino)-benzoic acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 6501 - 6504

27
[ 13194-68-8 ]
[ 446-30-0 ]
4-Chloro-2-(4-iodo-2-methyl-phenylamino)-benzoic acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 6501 - 6504

28
[ 13194-68-8 ]
[ 107-91-5 ]
(2E)-2-cyano-2-[(4-iodo-2-methylphenyl)hydrazono]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		[00653] Example 4: 4-[(aminocarbonyl) amino]-1-(4-iodo-2- methylphenyl)-1 H-pyrazole-3-carboxamide; [00655] Step 1: Preparation of (2E)-2-cyano-2- [ (4-iodo-2- methylphenyl) hydrazono] acetamide; [00657] Preparation of Solution A: 2-Methyl-4-iodoaniline (23.3 g, 100 mmol) was treated with conc. HCI (25 mL) and diluted with water (100 mL). This mixture was stirred and cooled to-5 to 0C in an ice/acetone bath. To this was added a solution of sodium nitrite (6.90 g, 100 mmol) in water (20 mL) at-5 to 0C. The resultant mixture was stirred 20 min. To this was added a-5C solution of sodium acetate trihydrate (40.8 g, 300 mmol) in water (100 mL). [00658] Preparation of Solution B: Separately, cyanoacetamide (10.1 g, 120 mmol) was dissolved in water (180 mL) and ethanol (120 mL). The solution was cooled to-5C. To this was added a cooled (-5C) solution of sodium acetate trihydrate (13.6 g, 100 mmol) in water (30 mL). [00659] Solution A was added by pipette dropwise over about 30 min to Solution B at 5C to make a pasty mixture. After 3 h the mixture was filtered. The solids were then washed with ether (500 mL) and dried further to give a yellow brown solid. NMR indicated a mixture of stereomers.

Reference： [1]Patent: WO2005/37797,2005,A1 .Location in patent: Page/Page column 192

29
[ 13194-68-8 ]
[ 762-04-9 ]
[ 42822-60-6 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine;tetrakis(triphenylphosphine) palladium(0); at 90℃;	A solution of <strong>[13194-68-8]4-iodo-2-methylaniline</strong> [CAS 13194-68-8] (0.51 g, 2.21 mmol), diethyl phosphonate (0.30 mL, 2.32 mmol), TEA (0.325 mL, 2.33 mmol), Pd(PPh3) (cat.) was heated at 90C overnight. The solution was cooled to room temperature and EtOAc was added. After standard aqueous work up, the crude was purified by MPLC (30-50% EtOAc/Hexanes) and used in the next step.

Reference： [1]Patent: WO2011/50054,2011,A2 .Location in patent: Page/Page column 47

30
[ 772-38-3 ]
[ 13194-68-8 ]
[ 1393820-27-3 ]

Yield	Reaction Conditions	Operation in experiment
	With N-butylamine;copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); In diethyl ether; for 6h;	<strong>[13194-68-8]4-iodo-2-methylbenzenamine</strong> 24 (233mg, 1 mmol ) on reaction with l-rert-butyl-4-ethynylbenzene (25b, 158 mg,l .mmol) by employing Sonagashira coupling conditions using Pd(PPh3)4 (69.3 mg, 0.06 equiv) as catalyst, Cul (22.8 mg, 0.12equiv) as cocatalyst, butyl amine (261 mg, 3 equiv)as base and ether as solvent and kept the reaction for 6h. After completion of the reaction as indicated by TLC and the reaction mixture is extracted into ether (4x25 mL) from the aqueous layer and concentrated in vacuo. The compound was further purified by column chromatography using 60-120 silica gel (ethyl acetate/hexane,l:9) to obtain 4-((4-tert-butylphenyl) ethynyl)-2-methyl benzene amine (26b) as pure product. Anthranilic acid (27, 137 mg, lmmol) on reaction with acetic anhydride at 150 C and reflux for 30 min, after completion of reaction aqueous sodium bicarbonate solution is added and extracted in ethyl acetate (4x25 mL) from the aqueous layer and concentrated in vacuo afforded 2-methyl 4H- benzo [cf] [l,3]oxazin-4-one compound (28) as pure product. To a stirred solution of 4-((4-tert- butylphenyl)ethynyl)-2-methylbenzenamine (26b, 263 mg, 1 mmol) with 2-methyl-4H- benzo[c ][l,3]oxazin-4-one (28, 161 mg, lmmol) in acetic acid and reflux for 8h After com pletion of the reaction as indicated by TLC. then the reaction mixture was quenched with NaHC03 and extracted in ethyl acetate (4x25 mL) from the ice cold aqueous layer and dried over anhydrous Na2S04 afforded 3-(4-((4-iert-butylphenyl)ethynyl)-2-methylphenyl)-2-methylquinazolin-4(3H)-one (29b). Reaction of 3-(4-((4-terf-butylphenyl)ethynyl)-2-methylphenyl)-2-methyl quinazolin-4(3H)-one (29b, 406 mg, lmmol) with 2,4-dihydroxybenzaldehyde (30d, 138 mg, lmmol) was taken in acetic acid Then the resulting mixture was stirred under reflux conditions for 8 h and then the reaction mixture was quenched with NaHC03 and extracted in ethyl acetate (4x25 mL) from the ice cold aqueous layer and dried over anhydrous Na2S04.The resulting product (5d) was purified by column chromatography employing EtOAc/Hexane as an eluent.Mp 93-95 C; JH NM R (CDCI3+DMSO-d6, 200 MHz) delta 8.23 (d, J = 15.9 Hz, 1H), 8.20 (s, 1H), 7.79-7.66 (m, 3H), 7.51-7.34 (m, 6H), 7.26 (s, 1H), 7.10 ( d, J = 8.3 Hz, 1H), 6.89 (d, J = 8.3 Hz, 1H), 6.21 (d, J = 15.2 Hz, 1H), 6.18 (s, 1H), 2.06 (s, 3H), 1.14 (s, 9H); LRMS(ESI, m/z) 527 (M)+
	With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); N-butylamine; In diethyl ether; at 25 - 30℃; for 6h;	<strong>[13194-68-8]4-iodo-2-methylbenzenamine</strong> 24 (233 mg, 1 mmol) on reaction with 1-tert-butyl-4-ethynylbenzene (25b, 158 mg, 1 mmol) by employing Sonagashira coupling conditions using Pd(PPh3)4 (69.3 mg, 0.06 equiv) as catalyst, Cul (22.8 mg, 0.12 equiv) as cocatalyst, butyl amine (261 mg, 3 equiv) as base and ether as solvent and kept the reaction for 6 h. After completion of the reaction as indicated by TLC and the reaction mixture is extracted into ether (4×25 mL) from the aqueous layer and concentrated in vacuo. The compound was further purified by column chromatography using 60-120 silica gel (ethyl acetate/hexane,1:9) to obtain 4-((4-tert-butylphenyl) ethynyl)-2-methyl benzene amine (26b) as pure product. Anthranilic acid (27, 137 mg, lmmol) on reaction with acetic anhydride at 150 C. and reflux for 30 min, after completion of reaction aqueous sodium bicarbonate solution is added and extracted in ethyl acetate (4×25 mL) from the aqueous layer and concentrated in vacuo afforded 2-methyl 4H-benzo[d][1,3]oxazin-4-one compound ( 28) as pure product. To a stirred solution of 4-((4-tertbutylphenyl)ethynyl)-2-methylbenzenamine (26b, 263 mg, 1 mmol) with 2-methyl-4H-benzo[d][1,3]oxazin-4-one (28, 161 mg, 1 mmol) in acetic acid and reflux for 8 h After completion of the reaction as indicated by TLC. then the reaction mixture was quenched with NaHCO3 and extracted in ethyl acetate (4×25 mL) from the ice cold aqueous layer and dried over anhydrous Na2SO4 afforded 3-(4-((4-tert-butylphenyl)ethynyl)-2-methylphenyl)-2-methylquinazolin-4(3H)-one (29b). Reaction of 3-(4-((4-tert-butylphenyl)ethynyl)-2-methylphenyl)-2-methylquinazolin-4(3H)-one (29b, 406 mg, 1 mmol) with 2,4-dihydroxybenzaldehyde (30d, 138 mg, 1 mmol) was taken in acetic acid Then the resulting mixture was stirred under reflux conditions for 8 h and then the reaction mixture was quenched with NaHCO3 and extracted in ethyl acetate (4×25 mL) from the ice cold aqueous layer and dried over anhydrous Na2SO4.The resulting product ( 5d) was purified by column chromatography employing EtOAc/Hexane as an eluent.

Reference： [1]Patent: WO2012/111017,2012,A1 .Location in patent: Page/Page column 21
[2]MedChemComm,2013,vol. 4,p. 575 - 581
[3]Patent: US2013/317221,2013,A1 .Location in patent: Page/Page column 0147; 0131; 0133; 0126

31
[ 13194-68-8 ]
[ 129113-00-4 ]
[ 1393820-28-4 ]

Yield	Reaction Conditions	Operation in experiment
	With N-butylamine;copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); In diethyl ether; for 6h;	<strong>[13194-68-8]4-iodo-2-methylbenzenamine</strong> 24 (233 mg, 1 mmol) on reaction with 2-ethynyl-6- methoxynaphthalene (25c, 182nig, 1 mmol) by employing Sonagashira coupling conditions using Pd(PPh3)4 (69.3 mg, 0.06 equiv) as catalyst, Cul (22.8 mg, 0.12 equiv) as cocatalyst, butyl amine (261 mg, 3 equiv) as base and ether as solvent and kept the reaction for 6h. After completion of the reaction as indicated by TLC and the reaction mixture is extracted into ether (4x25 mL) from the aqueous layer and concentrated in vacuo. The compound was further purified by column chromatography using 60-120 silica gel (ethyl acetate/hexane,l:9) to obtain 4-((6- methoxynaphthalen-2-yl)ethynyl)-2-methyl benzenamine (26c) as pure product. Anthranilic acid (27, 137 mg, lmmol) on reaction with acetic anhydride at 150 C a nd reflux for 30 min, after completion of reaction aqueous sodium bicarbonate solution is added and extracted in ethyl acetate (4x25 mL) from the aqueous layer and concentrated in vacuo afforded 2-methyl-4H-benzo [d] [l,3]oxazin-4-one compound (28) as pure product. To a stirred solution of 4-((6-methoxynaphthalen-2-yl)ethynyl)-2- methylbenzenamine (26c) with 2-methyl-4H-benzo[c/] [l,3]oxazin-4-one (28, 161 mg, lmmol) in acetic acid and reflux for 8h After completion of the reaction as indicated by TLC. then the reaction mixture was quenched with NaHC03 and extracted in ethyl acetate (4x25 m L) from the ice cold aqueous layer and dried over anhydrous Na2S04 afforded 3-(4-((6-methoxynaphthalen-2-yl)ethynyl)-2- methylphenyl)-2-'methylquinazolin-4(3H)-one (29c). Reaction of 3-(4-((6-methoxynaphthalen-2- yl)ethynyl)-2-methylphenyl)-2-methylquinazolin-4(3W)-one (29c, 430 mg, 1 mmol) with 3,4,5- trimethoxybenzaldehyde (301, 196 mg, 1 mmol) was taken in acetic acid Then the resulting mixture was stirred under reflux conditions for 8 h and then the reaction mixture was quenched with NaHC03 a nd extracted in ethyl acetate (4x25 mL) from the ice cold aqueous layer and dried over anhydrous Na2S04.The resulting product (61) was purified by column chromatography employing EtOAc/Hexane as an eluent.Mp 129-130 C; H N M R (CDCI3+DMSO- 6, 200 M Hz) delta 8.79 (t, =8.5, IH), 7.99 (s, IH), 7.87 (d, J =14.5 Hz, IH), 7.81-7.63 (m, 5H), 7.59-7.44 (m, 3H), 7.24 (d, J = 10.2 Hz, IH), 7.14 (dd, =2.9, 7,7 Hz, 2H), 7.08 (s, IH), 6.49 (s, IH), 6.41 (d, J = 15.3 Hz, IH), 3.93 (s, 3H), 3.80 (s, 9H), 2.20 (s, 3H); LRMS(ESI, m/z) 609 (M)+
	With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); N-butylamine; In diethyl ether; at 25 - 30℃; for 6h;	<strong>[13194-68-8]4-iodo-2-methylbenzenamine</strong> 24 (233 mg, 1 mmol) on reaction with 2-ethynyl-6-methoxynaphthalene (25c, 182 mg, 1 mmol) by employing Sonagashira coupling conditions using Pd(PPh3)4 (69.3 mg, 0.06 equiv) as catalyst, Cul (22.8 mg, 0.12 equiv) as cocatalyst, butyl amine (261 mg, 3 equiv) as base and ether as solvent and kept the reaction for 6 h. After completion of the reaction as indicated by TLC and the reaction mixture is extracted into ether (4×25 mL) from the aqueous layer and concentrated in vacuo. The compound was further purified by column chromatography using 60-120 silica gel (ethyl acetate/hexane,1:9) to obtain 4-((6-methoxynaphthalen-2-yl)ethynyl)-2-methyl benzenamine (26c) as pure product. Anthranilic acid (27, 137 mg, 1 mmol) on reaction with acetic anhydride at 150 C. and reflux for 30 min, after completion of reaction aqueous sodium bicarbonate solution is added and extracted in ethyl acetate (4×25 mL) from the aqueous layer and concentrated in vacuo afforded 2-methyl-4H-benzo [d][1,3]oxazin-4-one compound ( 28) as pure product. To a stirred solution of 4-((6-methoxynaphthalen-2-yl)ethynyl)-2-methylbenzenamine ( 26c) with 2-methyl-4H-benzo[d][1,3]oxazin-4-one (28, 161 mg, 1 mmol) in acetic acid and reflux for 8 h After completion of the reaction as indicated by TLC. then the reaction mixture was quenched with NaHCO3 and extracted in ethyl acetate (4×25 mL) from the ice cold aqueous layer and dried over anhydrous Na2SO4 afforded 3-(4-((6-methoxynaphthalen-2-yl(ethynyl)-2-methylphenyl)-2-methylquinazolin-4(3H)-one (29c). Reaction of 3-(4-((6-methoxynaphthalen-2-yl)ethynyl)-2-methylphenyl)-2-methylquinazolin-4(3H)-one (29c, 430 mg, 1 mmol) with 3,4,5-trimethoxybenzaldehyde (301, 196 mg, 1 mmol) was taken in acetic acid Then the resulting mixture was stirred under reflux conditions for 8 h and then the reaction mixture was quenched with NaHCO3 and extracted in ethyl acetate (4×25 mL) from the ice cold aqueous layer and dried over anhydrous Na2SO4.The resulting product ( 6l) was purified by column chromatography employing EtOAc/Hexane as an eluent.

Reference： [1]Patent: WO2012/111017,2012,A1 .Location in patent: Page/Page column 21-22
[2]MedChemComm,2013,vol. 4,p. 575 - 581
[3]Patent: US2013/317221,2013,A1 .Location in patent: Paragraph 0150; 0131; 0133; 0126

32
[ 123-75-1 ]
[ 13194-68-8 ]
[ 1394130-76-7 ]

Reference： [1]Organic Letters,2012,vol. 14,p. 4560 - 4563

33
[ 624-78-2 ]
[ 13194-68-8 ]
[ 149-73-5 ]
[ 1374427-73-2 ]

Yield	Reaction Conditions	Operation in experiment
1.8 g		Methyl orthoformate (24.1 g) and 0.19 g of p-toluenesulfonic acid monohydrate were added to 2.30 g of <strong>[13194-68-8]4-iodo-2-methylaniline</strong>, and the mixture was heated under reflux for 12 hours. The reaction solution was concentrated under reduced pressure, and the resulting residue was dissolved in 20 ml of dichloromethane. N-ethyl-methylamine (1.17 g) was added thereto, and the mixture was stirred at 25 C. for 15 hours. The reaction solution was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=4:1), thereby obtaining 1.80 g of N-ethyl-N-methyl-N?-(4-iodo-2-methylphenyl)formamidine (Compound 2-2). 1H NMR (300 MHz, CDCl3): 1.20 (t, 3H), 2.20 (s, 3H), 2.98 (s, 3H), 3.30 (brs, 2H), 6.48 (d, 1H), 7.35-7.37 (m, 2H), 7.43 (s, 1H)

Reference： [1]Patent: US2013/217884,2013,A1 .Location in patent: Paragraph 0136-0137

34
[ 13194-68-8 ]
[ 124-40-3 ]
[ 149-73-5 ]
[ 1374427-72-1 ]

Yield	Reaction Conditions	Operation in experiment
6.8 g		Methyl orthoformate (105 g) and 0.8 g of p-toluenesulfonic acid monohydrate were added to 10.0 g of <strong>[13194-68-8]4-iodo-2-methylaniline</strong>, and the mixture was heated under reflux for 12 hours. The reaction solution was concentrated under reduced pressure, and the resulting residue was dissolved in 50 ml of dichloromethane. A 50% dimethylamine aqueous solution (7.70 g) was added thereto, and the mixture was stirred at 25 C. for 15 hours. The reaction solution was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate 4:1), thereby obtaining 6.80 g of N,N-dimethyl-N?-(4-iodo-2-methylphenyl)formamidine (Compound 2-1). 1H NMR (300 MHz, CDCl3): 2.21 (s, 3H), 3.00 (s, 6H), 6.48 (d, 1H), 7.34-7.37 (m, 2H), 7.43 (s, 1H)

Reference： [1]Patent: US2013/217884,2013,A1 .Location in patent: Paragraph 0134-0135

35
[ 13194-68-8 ]
[ 202865-85-8 ]

Reference： [1]Chemical Communications,2014,vol. 50,p. 2136 - 2138

36
[ 13194-68-8 ]
[ 5460-09-3 ]
[ 1608997-41-6 ]

Yield	Reaction Conditions	Operation in experiment
18%		General procedure: Aniline derivative (1 eq) was mixed with iced water and/or absolute EtOH (2 mL by mmol of reagent) and stirred at 0 C then hydrochloric acid 37% (4 eq) was added dropwise rapidly. Sodium nitrite (1.1 eq or 1.3 eq aniline substituent depending) was added solid or in solution (H2O/EtOH 1 M) and the reaction mixture was stirred at 0-2 C for 30 min. The solvent was removed carefully under reduced pressure without heating and can be used without further purification. 5-Amino-4-hydroxynaphtalene-2,7-disulfonic acid sodium salt (0.9 eq) was dissolved in iced water (5 mL by mmol of reagent) then pH was adjusted to 9 by adding 30% NaOH solution. The diazonium salt was added to the naphthalene moiety and pH maintained at 9 by addition of 10% NaOH solution. After complete addition of the diazonium salt to the 5-amino-4-hydroxynaphthalene-2,7-disulfonic acid monosodium salt, stirring was maintained at 0 C for 2 h. Degraded diazonium was removed after extraction with EtOAc and water soluble diazo compounds were recrystallized three times from EtOH/(H2O; pH 2) (1/1). All organic impurities were then extracted by washing with small portions of Et2O. The precipitated compounds were dried under vacuum.

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 78,p. 236 - 247

37
[ 583-75-5 ]
[ 13194-68-8 ]

Yield	Reaction Conditions	Operation in experiment
90%	With copper(l) iodide; sodium iodide; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 110℃; for 18h;Inert atmosphere; Schlenk technique;	Aromatic Finkelstein Reaction; General ProcedureThe reaction was carried out under argon using standard Schlenktechniques due to the moisture and oxygen sensitivity of the copper(I) iodide. A two-neck pear-shaped flask equipped with a refluxcondenser was charged with the (het)aryl bromide starting material,NaI (2 equiv per bromine to exchange), and CuI (5 mol% per bromineto exchange). N,N?-Dimethylethylenediamine (L1) or N,N?-dimethyl-1,2-cyclohexanediamine (L2) (10 mol% per bromine toexchange) and anhydrous 1,4-dioxane (0.5 mL per 1 mmol NaI)were added. The resulting suspension was heated to 110 C for 18h. After cooling to r.t., the mixture was poured into aq 25% NH3 solution.The blue solution was diluted to a doubled volume with H2Oand was extracted three times with CH2Cl2. In the case of the 2,2?-bipyridines, the combined organic phases were additionally washedwith aq EDTA solution. Otherwise, the combined organic phaseswere solely washed with brine and dried with MgSO4. The solventwas removed under reduced pressure to give the desired product inpure form. If needed, the crude product can be purified by columnchromatography or recrystallization.

Reference： [1]Synthesis,2014,vol. 46,p. 1085 - 1090
[2]Journal of the American Chemical Society,2015,vol. 137,p. 8328 - 8331

38
[ 13194-68-8 ]
4,4′-diiodo-2,2'-dimethylazobenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
3%	With pyridine; copper(l) chloride; at 20℃; for 18h;	General procedure: A mixture of CuCl (5 g, 50.5 mmol) and pyridine (50 mL) was stirred at r.t. for 30 min. The suspension was filtered and the halogenated aniline (1.5 equiv) was added to the green solution. Air was bubbled through the solution for 18 h. The residue was diluted with CH2Cl2 (200 mL) and aq 1 M HCl (100 mL). The aqueous layer was extracted with CH2Cl2 (3 × 100 mL). The combined organic layers were washed with H2O (100 mL), dried (MgSO4), and concentrated.The crude product was recrystallized from EtOH.

Reference： [1]Synthesis,2014,vol. 46,p. 2376 - 2382

39
[ 13194-68-8 ]
[ 773865-48-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: 1 h / 100 °C 2.1: diphenylether / 0.75 h / 250 °C 3.1: sodium hydroxide / water; ethanol / 1 h / Reflux 3.2: 20 °C

Reference： [1]Ochiana, Stefan O.; Bland, Nicholas D.; Settimo, Luca; Campbell, Robert K.; Pollastri, Michael P. [Chemical Biology and Drug Design, 2015, vol. 85, # 5, p. 549 - 564]

40
[ 553-21-9 ]
[ 13194-68-8 ]
((3E,6E,10E,11aR)-3-(4-amino-3-methylbenzylidene)-6,10-dimethyl-3,3a,4,5,8,9-hexahydrocyclodeca[b]furan-2(11aH)-one) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With palladium diacetate; triethylamine; In N,N-dimethyl-formamide; at 20 - 80℃;Inert atmosphere;	General procedure: To a mixture of costunolide (0.04 mmol), triethylamine (0.12 mmol) and substituted aryl iodide (0.045 mmol) in DMF (200 muL) were added Palladium (II) acetate (0.002 mmol) at room temperature under inert atmosphere. The reaction mixture was then heated at 80-90 C for 14-16 h. The progress of the reaction was monitored by TLC; it indicated consumption of reactants. The reaction mixture was brought to room temperature and diluted with water (2 mL) and resultant mixture was extracted with Et2O (2 mL x 5). The combined organic layers were evaporated under reduced pressure and dried over Na2SO4 to get the crude mixture, which was purified by column chromatography using (100-200 silica gel mesh) to yield pure compounds.

Reference： [1]Medicinal Chemistry Research,2015,vol. 24,p. 2871 - 2878

41
[ 13194-68-8 ]
[ 29745-04-8 ]
3-((4-iodo-2-methylphenyl)carbamoyl)-7-oxabicyclo[2.2.1]heptane-2-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With triethylamine; In tetrahydrofuran; at 20℃; for 14h;	General procedure: To a solution of NCTD (1, 1.0 g, 5.95 mmol) dissolved in tetrahydrofuran (THF, 10 mL)accompanied by triethylamine (TEA, 0.5 mL) as the acid-binding agent was added the correspondingaromatic amine (1 equiv., 5.95 mmol). When the reaction was complete after 14 h as checkedby TLC analysis, the solution was concentrated under reduced pressure and diluted with acetone(100 mL). The resulting filter cake was either recrystallized from methanol or purified by columnchromatography (MeOH/CH2Cl2, 1: 4, v/v) to afford the desired products II (1-36). The yields,physical properties, 1H-NMR, 13C-NMR, and HRMS-ESI of the target compounds II were as follows.

Reference： [1]Molecules,2015,vol. 20,p. 21464 - 21480

42
[ 57294-38-9 ]
[ 13194-68-8 ]
4-(4-iodo-2-methylphenylamino)-4-oxobutylcarbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84.2%	With 2-(1H-9-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate; potassium carbonate; In acetonitrile; at 20℃; for 3h;	Under room temperature, will be sequentially 2-methyl-4-iodo aniline (4.46 g, 19.1 millimole), K2CO3(5.3 g, 38.4 mmol), 4 - (N-tert-butoxycarbonyl amino) butanoic acid (7 g, 34.4 mmol), 2 - (7-azobenzol and triazazole)-N, N, N ', N' -four methyl urea hexafluoro-phosphate (HATU) (8.7 g, 22.9 mmol) by adding acetonitrile in (50 ml). At the room temperature to the stirring reaction mixture of 3 hours. The obtained mixture is concentrated under reduced pressure, then adding water. The resulting mixture is extracted with ethyl acetate. The resulting organic phase is concentrated to obtain crude product. The resulting crude product is purified by silica gel column chromatography (dichloromethane: methanol =50:1) the white solid obtained 6.72 g, is the target compound (yield: 84.2%).

Reference： [1]Patent: CN105384739,2016,A .Location in patent: Paragraph 0275; 0276; 0277

43
[ 3350-78-5 ]
[ 13194-68-8 ]
N-(4-iodo-2-methylphenyl)-3-methylbut-2-enamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With pyridine; In dichloromethane; at 20℃; for 6h;	3,3-Dimethylacryloyl chloride (0.22 mL, 2.2 mmol) and pyridine (0.194 ml, 2.4 mmol) was added to a solution of <strong>[13194-68-8]4-iodo-2-methylaniline</strong> (11, 0.466 g, 2.0 mmol) in DCM (30 mL). The resultant solution was stirred at rt for 6 h, and then diluted with DCM. The organics were washed with sat. NH4Cl, H2O and brine, dried (MgSO4) and evaporated to give a crude white solid (0.60 g). This was purified by SiO2 chromatography (hexane/EtOAc 8:2, with 1% Et3N as eluent) to give compound 12 as a white solid (0.53 g, 84%): m.p. = 106-107oC;1H NMR (400 MHz; CDCl3) delta 1.90 (s, 3H), 2.19 (s, 3H), 2.20 (d, J = 1.2 Hz, 3H), 5.72 (br, 1H), 6.86 (br, 1H), 7.47-7.51 (m, 2H), 7.69 (br, 1H); 13C NMR (101 MHz; CDCl3) delta 17.6, 20.2, 27.6, 88.6, 118.4, 124.4, 130.8, 135.8,136.1, 139.1, 154.3, 165.1; IR (neat) max/cm-13293w, 2980w, 2940w, 1635s, 1508s, 1442m, 1390m, 1286s, 838s, 798m, 620w; MS(ES): m/z = 316.0[M+H]+; HRMS (ES) calcd. for C12H15INO [M+H]+: 316.0198, found 316.0200; Found: C, 45.76; H, 4.46; N 4.36. Calc. for C12H14INO: C, 45.73; H, 4.48; N 4.44%.

Reference： [1]Beilstein Journal of Organic Chemistry,2016,vol. 12,p. 1851 - 1862

44
[ 13194-68-8 ]
[ 1068-55-9 ]
[ 112121-89-8 ]

Yield	Reaction Conditions	Operation in experiment
12%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In tetrahydrofuran; at -78℃; for 4h;Reflux;	To a solution of <strong>[13194-68-8]4-iodo-2-methyl-aniline</strong> (4.0 g, 17 mmol) and Pd(dppf)2Cl2 (140 mg, 0.17 mmol) in THF (50 mL) was added isopropylmagnisium chloride (25.5 mL, 51.0 mmol) at -78 C and was reacted at reflux for 4 h. The reaction was quenched with a saturated solution of NH4ci, extracted with EtOAc, dried over anhydrous Na2SC>4, filtered, and concentrated to dryness. The residue was purified by flash column chromatography to give the title compound as a brown solid (320 mg, 12%). MS (ESI): mass calcd. for ci0Hi5N, 149.1; m/z found, 150.0 [M+H]+.
12%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In tetrahydrofuran; at -78℃; for 4h;Reflux;	To a solution of <strong>[13194-68-8]4-iodo-2-methyl-aniline</strong> (4.0 g, 17 mmol) and Pd (dppf) 2Cl 2 (140 mg, 0.17 mmol) in THF (50 mL) was added isopropylmagnisium chloride (25.5 mL, 51.0 mmol) at -78 and was reacted at reflux for 4 h. The reaction was quenched with a saturated solution of NH 4Cl, extracted with EtOAc, dried over anhydrous Na 2SO 4, filtered, and concentrated to dryness. The residue was purified by flash column chromatography to give the title compound as a brown solid (320 mg, 12%). MS (ESI) : mass calcd. for C 10H 15N, 149.1 m/z found, 150.0 [M+H] +.
320 mg	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In tetrahydrofuran; at -78℃; for 4h;Reflux;	To a solution of <strong>[13194-68-8]4-iodo-2-methylaniline</strong> (4.0 g, 17 mmol) and Pd(dppf Cl2 (140 mg, 0.17 mmol) in THF (50 mL) was added isopropylmagnisium chloride (25.5 mL, 51.0 mmol) at -78 C and was reacted at reflux for 4 h. The reaction was quenched with a saturated solution of NH4C1, extracted with EtOAc, dried over anhydrous Na2SC>4, filtered, and concentrated to dryness. The residue was purified by flash column chromatography to give the title Compound as a brown solid (320 mg).

320 mg

With bis-triphenylphosphine-palladium(II) chloride; In tetrahydrofuran; at -78℃; for 4h;Reflux;

To a solution of <strong>[13194-68-8]4-iodo-2-methylaniline</strong> (4.0 g, 17 mmol) and Pd(dppf)2C12 (140 mg, 0.17 mmol) in THF (50 mL) was added isopropylmagnisium chloride (25.5 mL, 51.0 mmol) at -78 C and was reacted at reflux for 4 h. The reaction was quenchedwith a saturated solution of NH4C1, extracted with EtOAc, dried over anhydrous Na2504, filtered,and concentrated to dryness. The residue was purified by flash column chromatography to give the title compound as a brown solid (320 mg).

Reference： [1]Patent: WO2017/100668,2017,A1 .Location in patent: Page/Page column 146; 147
[2]Patent: WO2018/103058,2018,A1 .Location in patent: Page/Page column 146
[3]Patent: WO2017/100662,2017,A1 .Location in patent: Page/Page column 115
[4]Patent: WO2018/103060,2018,A1 .Location in patent: Page/Page column 114

45
[ 13194-68-8 ]
[ 17341-93-4 ]
C₁₀H₉Cl₃INO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
> 95%	With sodium hydroxide; In water; ethyl acetate; at 0 - 20℃; for 1h;	Compound E (e.g., 4.3mmol) was added in ethyl acetate (e.g., 30mL), water (e.g., 30mL) and sodium hydroxide (e.g., 4.8mmol) were added and the resulting product was used for the subsequent reaction. 2, 2, 2-trichloroethyl chloroformate (e.g., 4.7mmol) was added dropwise to the above solution at 0-5C .Aftercompletionofdropping, the reaction was carried out at room temperature for 1 hour. The organic phase was separated, dried and concentrated under reduced pressure to obtain compound F, the yield was >95%.

Reference： [1]Patent: EP3357916,2018,A1 .Location in patent: Paragraph 0087; 0088

46
[ 1294009-26-9 ]
[ 13194-68-8 ]
(E)-2-methyl-4-(2-methylstyryl)aniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In 1,4-dioxane; water; at 90℃; for 4h;Inert atmosphere;	A mixture of 4,4,5,5-tetramethyl-2-[(E)-2-(o-tolyl)vinyl]-1,3,2-dioxaborolane (1.87 g, 4.10 mmol, 1 eq), <strong>[13194-68-8]4-iodo-2-methyl-aniline</strong> (959.18 mg, 4.12 mmol, 1.00 eq), Pd(dppf)Cl2 (299.71 mg, 410.00 mumol, 0.1 eq) and Cs2CO3 (4.00 g, 12.30 mmol, 3 eq) in 1,4-dioxane (20 mL) and H2O (10 mL) was stirred under N2 atmosphere at 90 C. for 4 h. The mixture was diluted with water (20 mL) and extracted with EtOAc (50 mL*3). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue which was purified by silica gel column chromatography (PE/EtOAc=20/1 to 5/1). The desired fraction was concentrated under reduced pressure to give 2-methyl-4-[(E)-2-(o-tolyl)vinyl]aniline (640 mg, 2.46 mmol, 60.1% yield, 86.0% purity) as a black brown solid. 1H NMR (400 MHz, CDCl3) delta ppm 7.54 (d, J=7.6 Hz, 1H), 7.27-7.08 (m, 6H), 6.89 (d, J=16.0 Hz, 1H), 6.66 (d, J=8.0 Hz, 1H), 3.68 (br s, 2H), 2.40 (s, 3H), 2.19 (s, 3H); ES-LCMS m/z 224.1 [M+H]+.

Reference： [1]Patent: US2019/55218,2019,A1 .Location in patent: Paragraph 0376; 0377; 0380; 0381; 0412; 0413; 0414; 0415

47
[ 16034-46-1 ]
[ 13194-68-8 ]
N-(4-iodo-2-methyl-phenyl)-2-methyl-pyrazole-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
33.1%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine; In ethyl acetate; at 60℃; for 19h;	To a solution of <strong>[13194-68-8]4-iodo-2-methyl-aniline</strong> (200 mg, 858.19 mumol, 1 eq) and 2-methylpyrazole-3-carboxylic acid (129.87 mg, 1.03 mmol, 1.2 eq) in EtOAc (10 mL) was added T3P (1.64 g, 2.57 mmol, 1.53 mL, 50%, 3.0 eq) and DIEA (332.74 mg, 2.57 mmol, 448.44 muL, 3.0 eq). The mixture was stirred at 60 C. for 3 h. The mixture was stirred at 60 C. for 16 h. The reaction mixture was diluted with NaHCO3 solution (20 mL), extracted with ethyl acetate (20 mL*3). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue which was purified on silica gel column chromatography (from PE/EtOAc=1/0 to 10/3, TLC: PE/EtOAc=3/1, Rf=0.49) to give the product of N-(4-iodo-2-methyl-phenyl)-2-methyl-pyrazole-3-carboxamide (100 mg, 284.34 mumol, 33.1% yield, 97.0% purity) as a white solid. 1H NMR (400 MHz, CDCl3) delta ppm 7.69 (d, J=8.4 Hz, 1H), 7.63-7.56 (m, 2H), 7.53 (d, J=2.2 Hz, 1H), 7.45 (br s, 1H), 6.64 (d, J=2.0 Hz, 1H), 4.23 (s, 3H), 2.28 (s, 3H); ES-LCMS m/z 341.8 [M+H]+.

Reference： [1]Patent: US2019/55218,2019,A1 .Location in patent: Paragraph 0392; 0393; 0394; 0395

48
[ 766-47-2 ]
[ 13194-68-8 ]
2-methyl-4-[2-(o-tolyl)ethynyl]aniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); N-butylamine; In tetrahydrofuran; at 20℃; for 16h;Inert atmosphere;	A mixture of 1-ethynyl-2-methyl-benzene (70 mg, 602.62 mumol, 75.92 muL, 1 eq), <strong>[13194-68-8]4-iodo-2-methyl-aniline</strong> (140.44 mg, 602.62 mumol, 1 eq), CuI (22.95 mg, 120.52 mumol, 0.2 eq), Pd(PPh3)4 (69.64 mg, 60.26 mumol, 0.1 eq) and butan-1-amine (132.23 mg, 1.81 mmol, 178.68 uL, 3 eq) in THF (5 mL) was degassed and purged with N2 for 3 times. The mixture was stirred at 20 C. for 16 h under N2. The reaction mixture was quenched by addition of water (50 mL), extracted with EtOAc (30 mL*3). The combined organic layers were washed with brine (10 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue which was purified by flash silica gel chromatography (from PE/EtOAc=1/0 to 5/1, TLC: PE/EtOAc=5/1, Rf=0.23) to yield 2-methyl-4-[2-(o-tolyl)ethynyl]aniline (100 mg, 451.88 mumol, 75.0% yield, 100% purity) as a yellow solid. 1H NMR (400 MHz, CDCl3) delta ppm 7.50-7.43 (m, 1H), 7.27-7.12 (m, 5H), 6.65 (d, J=8.2 Hz, 1H), 3.78 (s, 2H), 2.51 (s, 3H), 2.18 (s, 3H); ES-LCMS m/z 222.2 [M+H]+.

Reference： [1]Patent: US2019/55218,2019,A1 .Location in patent: Paragraph 0356; 0357; 0358; 0359

49
4-[(4-propenoyloxy)butyloxy]benzoic acid [ No CAS ]
[ 13194-68-8 ]
C₂₁H₂₂INO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
3.17 g		Compound 4 (5.67 g, 21.5 mmol) and dibutylhydroxytoluene (10 mg, 45 mumol) were dissolved in a mixed solution of toluene (10 ml) and dimethyl acetamide (10 ml). Thionyl chloride (1.50 ml, 20.7 mmol) was added dropwise to the resulting solution under ice cooling, and the solution was stirred at room temperature for 4 hours. Furthermore, a dimethyl acetamide solution (10 ml) of <strong>[13194-68-8]4-iodo-2-methylaniline</strong> (2.00 g, 8.58 mmol) was added dropwise to the resulting solution under ice cooling, and the solution was stirred at 80 C. for 2 hours. After cooling the solution to room temperature, 1 N hydrochloric acid was added to the solution, followed by extraction with ethyl acetate. The organic layer obtained by the extraction was washed once with aqueous sodium bicarbonate and once with saline, respectively, and sodium sulfate was added to the washed organic layer. The obtained organic layer was filtered to collect the filtrate, and then the solvent was distilled off from the filtrate under reduced pressure. The resulting residue was purified by flash column chromatography to obtain Compound 8 (3.17 g) as a white solid.

Reference： [1]Patent: US2019/177268,2019,A1 .Location in patent: Paragraph 0118; 0125; 0126

50
[ 13194-68-8 ]
[ 56-81-5 ]
4,4',4”-(propane-1,2,3-triyl)tris(2-methylaniline) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With sulfuric acid; In water; at 160℃; for 0.25h;Green chemistry;	A 35 mL Q-tube pressure tube, furnished by Q Labtech was charged with aniline derivative 3c-e(10 mmol) (2.23 g of 3c, 1.86 g of 3d, 1.41 g of 3e), 5 mL glycerol, 3 mL H2SO4, and 10 mL of water.A Teflon septum was placed on top of the tube, and an appropriate cap was used. The mixture washeated in an oil bath at 160 C for 15 min. After cooling at room temperature, pH was adjusted at 8-9by adding NaOH and the reaction mixture was extracted with ethyl acetate (2 20 mL). The combined organic layers were dried over MgSO4 and were then filtered and evaporated under reduced pressure.The crude residue was purified by column chromatograph (cyclohexane-EtOAc) on silica gel yieldingthe corresponding quinoline. 3.4.1. 4,40,4?-(propane-1,2,3-triyl)tris(2-methylaniline) 7Yellow crystals yield 75%. mp 178-180 C, 1H-NMR (DMSO-d6, 600 MHz) : delta= 2.00 (9H,s, 3-CH3),3.34 (5H, m, 2CH2 and CH aliphatic), 5.01 (6H, s, 3NH2), 6.42 (3H, d, Ar-H), 7.13-7.20 (6H, m, Ar-H),13C-NMR (150 MHz, DMSO-d6): : delta= 16.95 (3CH3), 74.0 (CH-aliphatic), 76.24 (2CH2-aliphatic), 116.27(3 ortho-C), 124.21 (3C-CH3), 134.63 (6 meta-C), 137.55 (3para-C), 146.53 (3C-NH2). EI-HRMS: m/z forC24H29N3, calcd. 359.2361, found: 359.2362.

Reference： [1]Molecules,2019,vol. 24

51
[ 108-31-6 ]
[ 13194-68-8 ]
N-(4-iodo-2-methylphenyl)maleimide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%		First, N-(4-(2,5-bicyclo[2.2.1]heptenyl)-2-methylphenyl)maleimide was synthesized in two stages. <strong>[13194-68-8]4-Iodo-2-methylaniline</strong> (5.33 g, 22.9 mmol) was dissolved in diethyl ether (20 mL), and slowly added dropwise at 0 C. to a diethyl ether solution (20 mL) of maleic anhydride (1.87 g, 19.1 mmol) in a nitrogen atmosphere. After stirring for two hours thereafter at room temperature, the precipitated solid was filtered out and washed with diethyl ether. The solid filtered out and sodium acetate (302 mg) were dissolved in acetic anhydride (30 mL) and stirred for three hours at 140 C. The solvent was distilled off under reduced pressure, water was added, and the solution was extracted by methylene chloride. The organic layer was dried using anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography using chloroform-hexane mixed solvent (mixture ratio 1:1) as the developing solvent, and N-(4-iodo-2-methylphenyl)maleimide (4.20 g, 13.4 mmol, 74%) was obtained as a white solid. The spectral data of N-(4-iodo-2-methylphenyl)maleimide were as follows. (0129) 1H NMR (400 MHz, CDCl3): delta 7.70 (s, 1H), 7.62 (d, J=8.4 Hz, 1H), 6.87 (s, 1H), 6.84 (d, J=8.4 Hz, 1H), 2.11 (s, 3H); 13C NMR (100 MHz, CDCl3): delta 169.0, 140.0, 138.8, 136.0, 134.4, 130.3, 129.8, 95.1, 17.6; HRMS (APCI, positive): [M+] calcd. for C11H8INO2, 312.9600; found 312.9606.

Reference： [1]Patent: US10442886,2019,B2 .Location in patent: Page/Page column 49-51

52
[ 13194-68-8 ]
[ 117832-09-4 ]

Yield	Reaction Conditions	Operation in experiment
	With iodine; sodium hydrogencarbonate In water; toluene at 25℃; for 3h;

Reference： [1]Ong, Jun-Yang; Ng, Xiao Qian; Lu, Shenci; Zhao, Yu [Organic Letters, 2020, vol. 22, # 16, p. 6447 - 6451]

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

[ CAS No. 13194-68-8 ] {[proInfo.proName]}

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[ 13194-68-8 ] Synthesis Path-Upstream 1~11

[ 13194-68-8 ] Synthesis Path-Downstream 1~52

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Aryls

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[ 13194-68-8 ]