[ CAS No. 643-28-7 ] {[proInfo.proName]}

Name: 643-28-7|2-Isopropylaniline|95%
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SKU: A318434
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Quality Control of [ 643-28-7 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 643-28-7 ]

CAS No. :	643-28-7	MDL No. :	MFCD00007720
Formula :	C₉H₁₃N	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	YKOLZVXSPGIIBJ-UHFFFAOYSA-N
M.W :	135.21	Pubchem ID :	12561
Synonyms :

Calculated chemistry of [ 643-28-7 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.33
Num. rotatable bonds :	1
Num. H-bond acceptors :	0.0
Num. H-bond donors :	1.0
Molar Refractivity :	45.43
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) :	-5.62 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.92
Log Po/w (XLOGP3) :	2.12
Log Po/w (WLOGP) :	2.4
Log Po/w (MLOGP) :	2.46
Log Po/w (SILICOS-IT) :	2.07
Consensus Log Po/w :	2.19

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-2.39
Solubility :	0.548 mg/ml ; 0.00406 mol/l
Class :	Soluble
Log S (Ali) :	-2.3
Solubility :	0.681 mg/ml ; 0.00504 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.83
Solubility :	0.2 mg/ml ; 0.00148 mol/l
Class :	Soluble

Medicinal Chemistry

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

Safety of [ 643-28-7 ]

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

Application In Synthesis of [ 643-28-7 ]

* 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 [ 643-28-7 ]
Downstream synthetic route of [ 643-28-7 ]

[ 643-28-7 ] Synthesis Path-Upstream 1~10

1
[ 201230-82-2 ]
[ 52562-19-3 ]
[ 19155-24-9 ]
[ 30696-28-7 ]
[ 643-28-7 ]

Reference： [1] Catalysis Science and Technology, 2013, vol. 3, # 11, p. 3000 - 3006

2
[ 643-28-7 ]
[ 7073-94-1 ]

Reference： [1] Dalton Transactions, 2006, # 46, p. 5464 - 5475
[2] Heteroatom Chemistry, 2010, vol. 21, # 5, p. 355 - 360
[3] Chemistry Letters, 2007, vol. 36, # 1, p. 72 - 73
[4] Recueil des Travaux Chimiques des Pays-Bas, 1960, vol. 79, p. 1211 - 1222
[5] Gazzetta Chimica Italiana, 1886, vol. 16, p. 114
[6] Gazzetta Chimica Italiana, 1886, vol. 16, p. 114
[7] Patent: US2010/234652, 2010, A1, . Location in patent: Page/Page column 6
[8] Heteroatom Chemistry, 2010, vol. 21, # 4, p. 265 - 270

3
[ 643-28-7 ]
[ 6502-22-3 ]

Reference： [1] Chemistry Letters, 2007, vol. 36, # 1, p. 72 - 73

4
[ 74-98-6 ]
[ 62-53-3 ]
[ 99-88-7 ]
[ 5369-16-4 ]
[ 643-28-7 ]

Reference： [1] Journal of the American Chemical Society, 1985, vol. 107, p. 1556 - 1561
[2] Journal of the American Chemical Society, 1985, vol. 107, p. 1556 - 1561

5
[ 98-82-8 ]
[ 99-88-7 ]
[ 5369-16-4 ]
[ 643-28-7 ]

Reference： [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1993, # 7, p. 867 - 870

6
[ 74-98-6 ]
[ 62-53-3 ]
[ 99-88-7 ]
[ 5369-16-4 ]
[ 768-52-5 ]
[ 643-28-7 ]

Reference： [1] Journal of the American Chemical Society, 1983, vol. 105, # 5, p. 1122 - 1126

7
[ 643-28-7 ]
[ 19099-54-8 ]

Yield	Reaction Conditions	Operation in experiment
73%	Stage #1: With sulfuric acid; sodium nitrite In water at -20℃; Stage #2: With potassium iodide In water for 18 h;	2-Isopropyl aniline (27.04 g, 0.2 mole) was diazotised in 25percent sulfuric acid (w/w 160 mL), with sodium nitrite (14 g) in water (26 mL) at -20° C. This was transferred to potassium iodide (100 g) in water (100 mL), and after 18 hours, sodium hydroxide (36 g) and water (125 mL) were added. The mixture was extracted with hexanes, and the hexanes extract was passed through a column of silica gel, and concentrated, 35.8 g (73percent). Mass spec: m/z 246 (M⁺). ¹H NMR (CDCl₃) δ ppm: 1.23 (d, 6H, 6.84 Hz), 3.18 (septet, 1H, 6.84 Hz), 6.86 (m, 1H), 7.28 (m, 2H), 7.82 (dd, 1H, 1.24 and 7.92 Hz).

Reference： [1] Patent: US10113065, 2018, B1, . Location in patent: Page/Page column 21
[2] Journal of the American Chemical Society, 1957, vol. 79, p. 1897,1900
[3] Bulletin of the Chemical Society of Japan, 1971, vol. 44, p. 266 - 270
[4] Journal of Organic Chemistry, 1997, vol. 62, # 16, p. 5651 - 5656
[5] Advanced Synthesis and Catalysis, 2008, vol. 350, # 14-15, p. 2179 - 2182

8
[ 643-28-7 ]
[ 60515-72-2 ]

Reference： [1] Gazzetta Chimica Italiana, 1886, vol. 16, p. 114
[2] Patent: WO2008/62182, 2008, A1,

9
[ 643-28-7 ]
[ 132475-93-5 ]

Yield	Reaction Conditions	Operation in experiment
81%	at 0℃; Cooling with ice	Example 1; Synthesis of target compound 1a (NEt-3IP) The scheme of production method in this Example will be shown in Figure 1.1) Synthesis of Intermediate A 2- isopropyl aniline (2.7 g, 20.0 mmol) and concentrated sulfuric acid (5 mL) were mixed under cooling in an ice bath, and then mixed acid (concentrated nitric acid : concentrated sulfuric acid = 2 : 5, 7 mL) was added while not allowing the temperature to increase beyond 0°C. Then, the completion of the reaction was confirmed on TLC (Thin Layer Chromatography) plates (ethyl acetate : n-hexane = 1 : 2). After neutralization was performed by using 2 N aqueous sodium hydroxide, the resultant solution was extracted with ethyl acetate (70 mL .x. 3). Organic layer was washed with water (100 mL .x. 2) and saturated saline solution (50 mL). After the obtained organic layer was dried using magnesium sulfate, the solvent was distilled off under reduced pressure to yield dark orange oil of Intermediate A (2.9 g, 81percent). ¹H NMR (500 MHz, CDCl₃) δ 7.60 (dd, 1 H, J = 8.5 Hz and 2.5 Hz, Ar-H), 7.50 (d, 1 H, J = 2.5 Hz, Ar-H), 7.24 (d, 1 H, J = 8.5 Hz, Ar-H), 3.95 (br s, 2 H, NH₂), 2.90 (sept, 1 H, J= 7.0 Hz, CH(CH₃)₂), 1.29 (d, 6 H, J = 7.0 Hz, CH(CH₃)₂).
16%	Stage #1: at 0℃;	Example 45 Synthesis of 2-isopropyl-5-nitroaniline 70percent HNO₃ (5.1 mL, 84.76 mmol, 1.2 equiv) was added dropwise to a mixture of 2-isopropylaniline (10 mL, 9.55 g, 70.63 mmol, 1 equiv) in 70 mL of conc. sulfuric acid at 0° C. The reaction mixture was stirred at this temperature for 30 minutes and then poured onto ice. The aqueous mixture was extracted with EtOAc (2*150 mL). The organic layers were combined and washed with sat'd NaHCO₃. After evaporation, the residue was purified by column chromatography on silica gel using EtOAc/hexanes (3/7) to give 2 g of product (16percent) as a dark red oil. ¹H NMR (CDCl₃, 300 MHz): δ 7.60 (dd, J=8.1, 2.7 Hz, 1H), 7.50 (d, J=2.7 Hz, 1H), 7.23 (d, J=8.7 Hz, 1H), 2.91 (sept, J=6.6 Hz, 1H), 1.28 (d, J=6.9 Hz, 6H); m/z=181 (M+H)⁺.

Reference： [1] European Journal of Organic Chemistry, 2009, # 5, p. 687 - 698
[2] Patent: EP2116523, 2009, A1, . Location in patent: Page/Page column 13; 34
[3] Patent: US2012/22092, 2012, A1, . Location in patent: Page/Page column 45
[4] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 3, p. 668 - 671
[5] Patent: WO2010/71885, 2010, A1, . Location in patent: Page/Page column 452-453

10
[ 643-28-7 ]
[ 1147014-97-8 ]

Reference： [1] Organic and Biomolecular Chemistry, 2013, vol. 11, # 19, p. 3116 - 3127

[ 643-28-7 ] Synthesis Path-Downstream 1~88

1
[ 108-24-7 ]
[ 643-28-7 ]
[ 19246-04-9 ]

Yield	Reaction Conditions	Operation in experiment
93%	In toluene at 20℃; for 0.75h; Cooling with ice; Inert atmosphere;
87%	With triethylamine In chloroform at 20℃; for 0.5h;
	With triethylamine	157-158, 174-175, 216 2-Isopropylaniline was converted to 2-isopropyl-4-nitrophenyl isothiocyanate according to Method A2a

	In acetic acid for 1h; Inert atmosphere; Reflux;
	With triethylamine In dichloromethane at 0 - 20℃;
	at 0 - 25℃;

Reference： [1]Renard, Emma; Moreau, Mathieu; Bellaye, Pierre-Simon; Guillemin, Mélanie; Collin, Bertrand; Prignon, Aurélie; Denat, Franck; Goncalves, Victor [Journal of Medicinal Chemistry, 2021, vol. 64, # 12, p. 8564 - 8578]
[2]Kitching, Matthew O.; Dixon, Olivia E.; Baumann, Marcus; Baxendale, Ian R. [European Journal of Organic Chemistry, 2017, vol. 2017, # 44, p. 6540 - 6553]
[3]Constam; Goldschmidt [Chemische Berichte, 1888, vol. 21, p. 1157]
[4]Current Patent Assignee: BAYER AG - US6353006, 2002, B1 Location in patent: Page column 121-122, 127-128, 141-142
[5]Wink, Christoph; Detert, Heiner [Journal of Physical Organic Chemistry, 2013, vol. 26, # 2, p. 144 - 150]
[6]Wang, Da-Wei; Lin, Hong-Yan; Cao, Run-Jie; Chen, Tao; Wu, Feng-Xu; Hao, Ge-Fei; Chen, Qiong; Yang, Wen-Chao; Yang, Guang-Fu [Journal of Agricultural and Food Chemistry, 2015, vol. 63, # 23, p. 5587 - 5596]
[7]Tõth, Balázs L.; Kovács, Szabolcs; Sályi, Gergå; Novák, Zoltán [Angewandte Chemie - International Edition, 2016, vol. 55, # 6, p. 1988 - 1992]

2
[ 643-28-7 ]
[ 19099-54-8 ]

Yield	Reaction Conditions	Operation in experiment
73%	Stage #1: 2-isopropylaniline With sulfuric acid; sodium nitrite In water at -20℃; Stage #2: With potassium iodide In water for 18h;	22 2-Isopropyl Iodobenzene 2-Isopropyl aniline (27.04 g, 0.2 mole) was diazotised in 25% sulfuric acid (w/w 160 mL), with sodium nitrite (14 g) in water (26 mL) at -20° C. This was transferred to potassium iodide (100 g) in water (100 mL), and after 18 hours, sodium hydroxide (36 g) and water (125 mL) were added. The mixture was extracted with hexanes, and the hexanes extract was passed through a column of silica gel, and concentrated, 35.8 g (73%). Mass spec: m/z 246 (M+). 1H NMR (CDCl3) δ ppm: 1.23 (d, 6H, 6.84 Hz), 3.18 (septet, 1H, 6.84 Hz), 6.86 (m, 1H), 7.28 (m, 2H), 7.82 (dd, 1H, 1.24 and 7.92 Hz).
	(i) (diazotization), (ii) KI; Multistep reaction;
	With hydrogenchloride; potassium iodide; sodium nitrite 1.) H₂O, 10 min, 2.) H₂O, rt, 5 h; Yield given. Multistep reaction;

With sulfuric acid; potassium iodide; sodium nitrite

Reference： [1]Current Patent Assignee: GOVERNMENT OF THE UNITED STATES - US10113065, 2018, B1 Location in patent: Page/Page column 21
[2]Brown et al. [Journal of the American Chemical Society, 1957, vol. 79, p. 1897,1900]
[3]Oki,M.; Yamamoto,G. [Bulletin of the Chemical Society of Japan, 1971, vol. 44, p. 266 - 270]
[4]Saito, Susumu; Kano, Taichi; Hatanaka, Keiko; Yamamoto, Hisashi [Journal of Organic Chemistry, 1997, vol. 62, # 16, p. 5651 - 5656]
[5]Della Ca', Nicola; Sassi, Giovanni; Catellani, Marta [Advanced Synthesis and Catalysis, 2008, vol. 350, # 14-15, p. 2179 - 2182]

3
[ 108-24-7 ]
[ 643-28-7 ]
[ 31539-91-0 ]

Yield	Reaction Conditions	Operation in experiment
26%	Stage #1: acetic anhydride; 2-isopropylaniline at 0℃; for 1h; Stage #2: With nitric acid at 0℃; for 0.5h; Stage #3: With potassium hydroxide In ethanol; water for 0.25h;	30 Reference Example 30: N-(2-Isopropyl-4-nitro-phenyl)-acetamide. 2-Isopropyl aniline (10 g, 74 mmol) was added to ice-cold acetic anhydride (75 mL) and stirred for 1 hr airθ °C. Concentrated nitric acid (10 mL, 159 mmol) was added dropwise and the reaction mass stirred at this temp for a further 30 min. It was then poured into ice-cold water and the precipitated solid was filtered off. The resulting solid was added to a solution of potassium hydroxide (12 g) in a mixture of water (115 mL) and absolute ethanol (25 mL) and stirred for 15 min. The solid was filtered off and washed thoroughly with water to afford iV-(2-isopropyl-4-nitro-phenyl)- acetamide (4.3 g, 26%) as a solid.
	With nitric acid

Reference： [1]Current Patent Assignee: F2G BRITISH BODY CORPORATE; F2G LTD - WO2008/62182, 2008, A1 Location in patent: Page/Page column 118
[2]Oki,M.; Yamamoto,G. [Bulletin of the Chemical Society of Japan, 1971, vol. 44, p. 266 - 270]

4
[ 643-28-7 ]
[ 35774-48-2 ]

Yield	Reaction Conditions	Operation in experiment
82%	With tert.-butylnitrite; trimethylsilylazide In acetonitrile at 0 - 20℃; for 1h;
80%	With 2-Methyl-2-nitropropane; trimethylsilylazide In acetonitrile at 20℃; Inert atmosphere;
80%	Stage #1: 2-isopropylaniline With hydrogenchloride; NaNO₂ In water monomer at 0℃; for 2h; Stage #2: With Caswell No_. 744A In water monomer at 0℃; for 2h;

75%	Stage #1: 2-isopropylaniline With hydrogenchloride In water monomer at 0℃; Stage #2: With NaNO₂ In water monomer at 0 - 5℃; Stage #3: With Caswell No_. 744A In water monomer at 0 - 20℃;
72%	With tert.-butylnitrite; trimethylsilylazide In acetonitrile at 60℃; for 0.833333h;
	(i) (diazotization), (ii) NaN₃; Multistep reaction;
	With tert.-butylnitrite; trimethylsilylazide In acetonitrile at 60℃; for 4.66667h; Automated synthesizer;
	Stage #1: 2-isopropylaniline With hydrogenchloride; NaNO₂ In water monomer; ethyl acetate at 0℃; for 1h; Stage #2: With Caswell No_. 744A In water monomer; ethyl acetate at 20℃; for 4h;
	Stage #1: 2-isopropylaniline With hydrogenchloride; NaNO₂ In water monomer at 0 - 5℃; for 0.5h; Stage #2: With Caswell No_. 744A In water monomer at 0 - 20℃;	General procedure for the preparation of 5. General procedure: Compound 4(10 mmol) was dissolved in HCl (6 mol/mL, 10 mL) at 0 °C. To theabove reaction mixture, the solution of sodium nitrite (0.6 g,8.5 mmol) in H2O (25 mL) was added dropwise at 5 to 0 °C within30 min. The solution was vigorously stirred at 0-5 °C for 30 min. Sodium azide (40 mmol) in H2O (50 mL) was added dropwise intothe reaction mixture at 0-5 °C. The resulting solution was stirred at room temperature for 2-4 h followed by diluting with ice water(200 mL) and extracting with EtOAc (3 x 100 mL). The combined organic layer was washed with water (2 x 60 mL), saturated aqueous NaHCO3 (2 x 60 mL) and brine (2 x 50 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo to afford compound 5. The residual crude product was used directly without purification.
	Stage #1: 2-isopropylaniline With hydrogenchloride; NaNO₂ In water monomer at 0℃; for 0.5h; Stage #2: With Caswell No_. 744A; anhydrous Sodium acetate In water monomer at 0℃; for 0.5h;

Reference： [1]Alt, Isabel T.; Guttroff, Claudia; Plietker, Bernd [Angewandte Chemie - International Edition, 2017, vol. 56, # 35, p. 10582 - 10586][Angew. Chem., 2017, vol. 129, p. 10718 - 10722]
[2]Nguyen, Quyen; Sun, Ke; Driver, Tom G. [Journal of the American Chemical Society, 2012, vol. 134, # 17, p. 7262 - 7265]
[3]Sebest, Filip; Radtanajiravong, Lalita; Kaukver, Siim; White, Andrew J. P.; Díez-González, Silvia [Chemical Communications, 2022, vol. 58, # 22, p. 3681 - 3684]
[4]Kwok, Sen W.; Fotsing, Joseph R.; Fraser, Rebecca J.; Rodionov, Valentin O.; Fokin, Valery V. [Organic Letters, 2010, vol. 12, # 19, p. 4217 - 4219]
[5]Smith, Catherine J.; Smith, Christopher D.; Nikbin, Nikzad; Ley, Steven V.; Baxendale, Ian R. [Organic and Biomolecular Chemistry, 2011, vol. 9, # 6, p. 1927 - 1937]
[6]Smolinsky,G. [Journal of the American Chemical Society, 1961, vol. 83, p. 2489 - 2493]
[7]Smith, Catherine J.; Nikbin, Nikzad; Ley, Steven V.; Lange, Heiko; Baxendale, Ian R. [Organic and Biomolecular Chemistry, 2011, vol. 9, # 6, p. 1938 - 1947]
[8]Xu, Shilin; Zhuang, Xiaoxi; Pan, Xiaofen; Zhang, Zhang; Duan, Lei; Liu, Yingxue; Zhang, Lianwen; Ren, Xiaomei; Ding, Ke [Journal of Medicinal Chemistry, 2013, vol. 56, # 11, p. 4631 - 4640]
[9]Li, Jinyu; Nie, Cunbin; Qiao, Yue; Hu, Jing; Li, Qifei; Wang, Qiang; Pu, Xiaohui; Yan, Lin; Qian, Hai [European Journal of Medicinal Chemistry, 2019, vol. 178, p. 433 - 445]
[10]Boonsombat, Jutatip; Charoensuksai, Purin; Chuaypen, Natthaya; Limpachayaporn, Panupun; Oekchuae, Sittisak; Ruchirawat, Somsak; Sirirak, Jitnapa; Suksamrarn, Apichart; Tangkijvanich, Pisit; Wongprayoon, Pawaris [Pharmaceuticals, 2022, vol. 15, # 5]

5
[ 56-81-5 ]
[ 643-28-7 ]
[ 6457-30-3 ]

Yield	Reaction Conditions	Operation in experiment
89%	With sulfuric acid; potassium iodide In water at 145℃; for 15h;	Synthesis of 8-Alkylquinolines 8-Alkylquinolines wereprepared according to the Skraup method from 2-alkylanilines.To a solution of 2-isopropylaniline (1.35 g, 10mmol) and potassium iodide (215 mg, 1.3mmol) in glycerin (1.1 g, 120mmol), 80% aqueous sulfuric acid (5.5 g, 44.9mmol) was added dropwise over 3min. with vigorous stirring. The resultant mixture was heated at 145 °C for 15 h. The reaction mixture was poured into ice-water (30 mL), and then neutralized with 2Maqueous sodium hydroxide solution. The mixture was extracted with ethyl acetate (30mL 3), and the combined organic layer was washed with brine (100mL 1), dried over magnesiumsulfate, and concentrated under reduced pressure. The residuewas treated with column chromatography on silica gel to afford8-isopropylquinoline (eluted with hexane/ethyl acetate = 95/5,1.51 g, 8.9mmol, 89%) as a colorless oil. When other anilineswere used, reactions were conducted in the same way.
75%	With ferrous(II) sulfate heptahydrate; sulfuric acid; boric acid In nitrobenzene at 0 - 150℃; for 12h; Inert atmosphere;
75%	With ferrous(II) sulfate heptahydrate; sulfuric acid; boric acid In nitrobenzene at 0 - 150℃; for 11h;	1 [Preparation Example 11 Preparation of 8-isopropylguinoline A boric acid (4.1 mmol, 1.0 eq) and glycerol (16 mmol, 4.Oeq) were added to a mixture of FeSO4•H20 (0.49 mmol, 0.12 eq), 2-isopropyl aniline (4.1 mmol, 1.0 eq) and nitro-benzene (0.25 mL) at room temperature. The reaction mixture was cooled to 0°C, and a concentrated sulfuric acid (14 mmol, 3.3 eq) was slowly added thereto. Then, the reaction mixture was heated to 150°C, and stirred for 11 hours. After the stirring was completed, the reaction mixture was cooled to room temperature, and water (2 mL) and saturated NaHCO3 aqueous solution (4 mL) were added thereto to thereby complete the reaction. Then, the reaction mixture was extracted with diethylether (10 mL x 3), the obtained organic layer was washed with brine (30 mL x 2), dried with anhydrous MgSO4, followed by filtration and decompression concentration, and the residue was purified by silica gel column chromatography (EA/Hx = 1/20) to obtain 8-isopropylquinoline (527 mg, 75%).Colorless oil; 1H NMR (600 MHz, CDC13) ö 8.95 (dd, J= 4.2, 1.8 Hz, 1H), 8.12 (dd,J= 8.2, 1.7 Hz, 1H), 7.64 (ddd, J= 12.0, 7.7, 1.4 Hz, 2H), 7.51 (dd, J= 7.6, 7.6 Hz,1H), 7.37 (dd, J= 8.2, 4.1 Hz, 1H), 4.38 (sep, J= 6.9 Hz, 1H), 1.41 (d, J= 7.0 Hz,6H); 13C NMR (150 MHz, CDC13) ö 149.1, 147.3, 146.1, 136.4, 128.3, 126.4, 125.5,125.1, 120.7, 27.1, 23.5 (2C); JR (cm1) 2959, 2867, 1596, 1496, 1467, 1364, 1324, 1250, 1177, 1133, 1108, 1046, 1016, 828, 791, 755, 687; HRMS (El): CalculatedforC12H13N [Mj: 171.1048, Found: 171.1047.

70%	Stage #1: glycerol; 2-isopropylaniline With ferrous(II) sulfate heptahydrate; sulfuric acid; boric acid In nitrobenzene at 150℃; for 20h; Cooling with ice; Stage #2: With sodium hydroxide In water; nitrobenzene
56%	With arsenic(V) oxide; sulfuric acid Heating;
	With ferrous(II) sulfate heptahydrate; dihydroxyborane; sulfuric acid In nitrobenzene at 120℃; for 20h; Inert atmosphere;
	With ferrous(II) sulfate heptahydrate; sulfuric acid; boric acid; nitrobenzene at 150℃; for 20h;

Reference： [1]Iwai, Kento; Yokoyama, Soichi; Asahara, Haruyasu; Nishiwaki, Nagatoshi [Bulletin of the Chemical Society of Japan, 2020, vol. 93, # 1, p. 50 - 57]
[2]Gandhamsetty, Narasimhulu; Joung, Seewon; Park, Sung-Woo; Park, Sehoon; Chang, Sukbok [Journal of the American Chemical Society, 2014, vol. 136, # 48, p. 16780 - 16783]
[3]Current Patent Assignee: KAIST; INSTITUTE FOR BASIC SCIENCE - WO2016/76479, 2016, A1 Location in patent: Paragraph 237; 238; 239; 240
[4]Lu, Biao; Li, Chaoqun; Zhang, Liming [Journal of the American Chemical Society, 2010, vol. 132, # 40, p. 14070 - 14072]
[5]Hoenel, Michael; Vierhapper, Friedrich W. [Journal of the Chemical Society. Perkin transactions I, 1980, p. 1933 - 1939]
[6]Ma, Wenpeng; Zhang, Jianwei; Xu, Cong; Chen, Fei; He, Yan-Mei; Fan, Qing-Hua [Angewandte Chemie - International Edition, 2016, vol. 55, # 41, p. 12891 - 12894][Angew. Chem., 2016, vol. 128, p. 13083 - 13086,4]
[7]Rubio-Presa, Rubén; Fernández-Rodríguez, Manuel A.; Pedrosa, María R.; Arnáiz, Francisco J.; Sanz, Roberto [Advanced Synthesis and Catalysis, 2017, vol. 359, # 10, p. 1752 - 1757]

6
[ 506-68-3 ]
[ 643-28-7 ]
[ 137881-15-3 ]

Yield	Reaction Conditions	Operation in experiment
64%	In diethyl ether for 2.5h;	20 A mixture of cyanogen bromide (1.89 g, 17.9 mmol) and 2-isopropylaniline (3.875 g, 28.65 mmol) in diethylether (25 mL) was stirred for 2.5 hours under nitrogen atmosphere. The aniline hydrobromide was filtered, the diethylether evaporated, and the residue flash chromatographed using 4/1 Hexane/acetone to give (1.85 g, 64%) the title compound. HRMS: calcd for C10H11BrN2+H+, 183.08927; found (ESI-FTMS, [M+Na]), 183.08928.
64%	In diethyl ether for 2.5h;	32 Example 32 [4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-2-isopropylphenyl]cyanamide A mixture of cyanogen bromide (1.89 g, 17.9 mmol) and 2-isopropylaniline (30.875 g, 28.65 mmol) in diethylether (25 mL) was stirred for 2.5 hours under nitrogen atmosphere. The mixture was filtered, the filtrate evaporated, and the residue flash chromatographed using 4/1 Hexane/acetone to give (1.85 g, 64%) the title compound. HRMS: calcd for C10H11BrN2+H+, 183.08927; found (ESI-FTMS, [M+Na]), 183.08928.
27%		7.a Preparation of N-(1-naphthyl)-N'-(o-isopropylphenyl)guanidine (Compound VIII) a. o-Isopropylphenylcyanamide. A solution of cyanogen bromide (3.79 g, 35.8 mmol) in ether (50 ml) was added slowly to a stirred solution of o-isopropylaniline (7.75 g, 57.3 mmol) in ether (150 ml) and then heated to reflux at 45° C. for 2.5 hours and at room temperature for 6 hours. A white precipitate of o-isopropylaniline hydrobromide was filtered off, and the filtrate was washed with water (2*20 ml) and dried over Na2 SO4. It was filtered and concentrated and the residue was purified by flash chromatography on Si2 O to give o-isopropylphenylcyanamide (2.5 g, 27%) as very light yellow crystals. mp 75°-77° C. IR (CHCl3): 2230, 3410 cm-1.

	In diethyl ether for 6h; Ambient temperature;
	With caesium carbonate In methanol at 0 - 20℃; Inert atmosphere;

Reference： [1]Current Patent Assignee: PFIZER INC - US2007/27125, 2007, A1 Location in patent: Page/Page column 12
[2]Current Patent Assignee: PFIZER INC - US2007/27201, 2007, A1 Location in patent: Page/Page column 16
[3]Current Patent Assignee: OREGON STATE BOARD OF HIGHER EDUCATION - US5093525, 1992, A Current Patent Assignee: STAE OF OREGON; UNIV DE CIENCIAS DE LA SALUD; THROUGH THE OREGON STATE BOARD; OREGON STATE BOARD OF HIGHER EDUCATION - US5190976, 1993, A
[4]Reddy, N. Laxma; Hu, Lain-Yen; Cotter, Ronald E.; Fischer, James B.; Wong, Wen Jee; et al. [Journal of Medicinal Chemistry, 1994, vol. 37, # 2, p. 260 - 267]
[5]Li, Wen-Cheng; Liao, Wei-Wei; Sun, Yun-Hai; Wei, Zhong-Lin; Wu, Yu-Heng; Xi, Ji-Ming [Organic Letters, 2022, vol. 24, # 4, p. 1110 - 1115]

7
[ 643-28-7 ]
[ 76842-13-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium acetate; Iodine monochloride In acetic acid for 1h; Ambient temperature; Yield given;
	With sodium acetate; Iodine monochloride In acetic acid	86 4-Iodo-2-[prop-2-yl]aniline STR198 PREPARATION 86 4-Iodo-2-[prop-2-yl]aniline STR198 Iodine monochloride (12.9 cm3) was added at room temperature to a stirred solution of 2-[prop-2-yl]-aniline (27.0 g) and sodium acetate (16.4 g) in acetic acid (250 cm3). After 1 hour, volatile material was removed in vacuo and the residue was partitioned between ethyl acetate (200 cm3) and 10% sodium carbonate solution (50 cm3). The dried (MgSO4) organic extract was filtered and evaporated in vacuo to afford an oil which was chromatographed on silica (Merck "MK 60.9385") eluding with hexane. Combination and evaporation of the product containing fractions gave the product as a crude dark unstable oil (38 g) which was not characterised fully but was used directly in Preparation 84.
	With iodine; sodium hydrogencarbonate	210, 251 2-Isopropylaniline was converted to 4-iodo-2-isopropylaniline according to Method A5a

	Stage #1: 2-isopropylaniline With sodium acetate; Iodine monochloride In acetic acid at 20℃; for 0.333333h; Stage #2: With sodium hydrogencarbonate In water; acetic acid; ethyl acetate	92 To a solution of 2-isopropyl-phenylamine (262 mg, 1.94 mmol) and sodium acetate (159 mg, 1.94 mmol) in 5 mL acetic acid, was added iodide monochloride (409 mg, 2. 58 mmol) at room temperature. The mixture was stirred at room temperature for 20 minutes, then diluted with ethyl acetate and washed with saturated sodium bicarbonate. The organic layers were combined and concentrated in vacuo to give a crude residue, which was purified by column chromatography (silica 5-25% EtOAc/hexane) to give 4-iodo-2- isopropyl-phenylamine.
	With iodine; sodium hydrogencarbonate In water at 20℃; for 1.5h;

Reference： [1]Alabaster; Bell; Campbell; Ellis; Henderson; Roberts; Ruddock; Samuels; Stefaniak [Journal of Medicinal Chemistry, 1988, vol. 31, # 10, p. 2048 - 2056]
[2]Current Patent Assignee: PFIZER INC - US4710507, 1987, A
[3]Current Patent Assignee: BAYER AG - US6353006, 2002, B1 Location in patent: Page column 139, 154
[4]Current Patent Assignee: ASTRAZENECA PLC - WO2005/35520, 2005, A1 Location in patent: Page/Page column 75
[5]Huang, Jing; Sun, Ning; Chen, Pengyu; Tang, Runli; Li, Qianqian; Ma, Dongge; Li, Zhen [Chemical Communications, 2014, vol. 50, # 17, p. 2136 - 2138]

8
[ 643-28-7 ]
[ 214470-55-0 ]
4-(2-isopropyl-phenylamino)-6,7-dimethoxy-quinoline-3-carbonitrile [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 3244 - 3256

9
[ 7073-94-1 ]
[ 643-28-7 ]

Yield	Reaction Conditions	Operation in experiment
93%	With bis(tri-ortho-tolylphosphine)palladium⁽⁰⁾; (R)-(-)-1-[(S)-2-(dicyclohexylphosphino)ferrocenyl]ethyl-di-tert-butylphosphine; ammonia; sodium t-butanolate In 1,4-dioxane at 80℃; for 4h; Inert atmosphere;
90%	With tris(dibenzylideneacetone)dipalladium ⁽⁰⁾; lithium hexamethyldisilazane; CyJohnPhos In toluene at 100℃; for 20h;
89%	With ammonia; sodium t-butanolate In 1,2-dimethoxyethane at 90℃; for 20h;

82%	With copper(I) oxide; ammonium hydroxide In 1-methyl-pyrrolidin-2-one at 90℃; for 48h;
78%	With C₂₈H₃₀Cl₅N₃Pd; ammonia; lithium isopropoxide; sodium t-butanolate In 1,4-dioxane at 100℃; for 2h; Inert atmosphere; Schlenk technique;

Reference： [1]Vo, Giang D.; Hartwig, John F. [Journal of the American Chemical Society, 2009, vol. 131, # 31, p. 11049 - 11061]
[2]Huang; Buchwald [Organic letters, 2001, vol. 3, # 21, p. 3417 - 3419]
[3]Shen, Qilong; Hartwig, John F. [Journal of the American Chemical Society, 2006, vol. 128, # 31, p. 10028 - 10029]
[4]Xu, Hanhui; Wolf, Christian [Chemical Communications, 2009, # 21, p. 3035 - 3037]
[5]Lombardi, Christopher; Day, Jonathan; Chandrasoma, Nalin; Mitchell, David; Rodriguez, Michael J.; Farmer, Jennifer L.; Organ, Michael G. [Organometallics, 2017, vol. 36, # 2, p. 251 - 254]

10
[ 643-28-7 ]
[ 123-73-9 ]
[ 72804-94-5 ]

Yield	Reaction Conditions	Operation in experiment
74%	With hydrogenchloride In water; toluene for 16h; Reflux;	3.3. Synthesis of 8-(tert-Butyl)-2-methylquinoline (3c), 8-(iso-Propyl)-2-methylquinoline (3d) and8-Nitroquinoline (4a) General procedure: Toluene (50 mL) and crotonaldehyde (2.6 mL, 2.2 g, 31.4 mmol) were added to a solutionof 2-(tert-butyl)aniline (2.3 g, 15.7 mmol) in aqueous 6MHCl (200 mL) and were heatedunder reflux for 16 h. The mixture was allowed to cool to room temperature. The aqueouslayer was separated and neutralized with an aqueous solution of K2CO3. After extractionwith CH2Cl2 (3 50 mL), the organic layer was separated and dried over MgSO4,and then was filtered and distilled bp 110-115 C/ 3 mmHg. The liquid was purified bycrystallization from hexane to afford white crystals:8-(tert-Butyl)-2-methylquinoline (3c) [18] 2.4 g (12.2 mmol, 78%); mp = 55.1-56.3 C;1H-NMR (CDCl3; 400.2 MHz) = 1.68 (s, 9H, C(CH3)3), 2.72 (s, 3H, CH3), 7.21 (d,3JH,H =8.4 Hz, 1H, aromatic), 7.36 (t,3JH,H = 7.7 Hz, 1H, aromatic), 7.60 (m, 2H, aromatic), 7.98(d,3JH,H = 8.4 Hz, 1H, aromatic); 13C{1H}-NMR (CDCl3; 100.6 MHz) = 25.5, 31.0, 36.5,120.6, 125.0, 125.8, 126.3, 127.2, 136.4, 146.9, 147.5, 155.6.
70%	With hydrogenchloride

Reference： [1]Książek, Maria; Kubíček, Vladimír; Kusz, Joachim; Małecki, Jan Grzegorz; Nycz, Jacek E.; Swoboda, Daniel; Wantulok, Jakub [Molecules, 2021, vol. 26, # 7]
[2]Kikuchi, Kouichi; Tagami, Katsuya; Hibi, Shigeki; Yoshimura, Hiroyuki; Tokuhara, Naoki; Tai, Kenji; Hida, Takayuki; Yamauchi, Toshihiko; Nagai, Mitsuo [Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 9, p. 1215 - 1218]

11
[ 643-28-7 ]
[ 118-91-2 ]
[ 55751-56-9 ]

Yield	Reaction Conditions	Operation in experiment
73%	With copper(I) oxide; copper; potassium carbonate In 2-methoxy-ethanol for 2h; Heating;
73%	With copper(I) oxide; copper; potassium carbonate In 2-ethoxy-ethanol at 130℃; for 24h;
73%	With copper(I) oxide; copper; potassium carbonate In ethyl methyl ether for 2h; Heating / reflux;	1 2-(2'-Isopropylphenylamino)benzoic acid, 8; A mixture of 2-isopropylaniline (3.4 g, 25 mmol), 2-chlorobenzoic acid (3.8 g, 24 mmol), K2CO3 (4.1 g, 30 mmol), Cu powder (0.05 g), Cu2O (0.05 g), in 5 mL 2-methoxyethanol was refluxed for 2 hours. The cooled reaction mixture was poured into 30 mL water. Charcoal was then added and the solution was filtrated through Celite. The crude product was obtained by acidification of the filtrate with diluted HCl at ambient temperature, and subsequent recrystallization from acetone/water (1/8). The crystals were dissolved in 100 mL 5% aqueous Na2CO3, filtered through Celite and the crystals were recrystallized by acidification to yield acid 8 (4.4 g, 73%) as a white powder. 1H-NMR 8=1.22 (d, J=6.9 Hz, 6H), 3.21 (sept, J=6.9 Hz, 1H), 4.68 (bs, 1H), 6.68 (dd, J=7.2 Hz, J=7.4 Hz, 1H), 6.81 (d, J=8.2 Hz, 1H), 7.22-7.40 (m, 4H), 8.1 (dd, J=1.7 Hz, J=8.2 Hz, 1H), 9.18 (s, 1H). 13C-NMR δ=23.97, 28.83, 114.38, 117.09, 126.72, 126.90, 127.13, 127.31, 133.08, 135.68, 136.04, 137.84, 145.09, 151.20, 174.73.

Reference： [1]Wolf, Christian; Mei, Xuefeng [Journal of the American Chemical Society, 2003, vol. 125, # 35, p. 10651 - 10658]
[2]Mei, Xuefeng; August, Adam T.; Wolf, Christian [Journal of Organic Chemistry, 2006, vol. 71, # 1, p. 142 - 149]
[3]Current Patent Assignee: GEORGETOWN UNIVERSITY - US2007/276140, 2007, A1 Location in patent: Page/Page column 20

12
[ 79-04-9 ]
[ 643-28-7 ]
[ 57503-03-4 ]

Yield	Reaction Conditions	Operation in experiment
94%	With sodium hydrogencarbonate In ethyl acetate at 20℃; for 1.66667h; Cooling with ice;	2.1 Step 1. 2-Chloro-N-(2-isopropylphenyl)acetamide (C₉) Step 1. 2-Chloro-N-(2-isopropylphenyl)acetamide (C9) To a stirred solution of 2-isopropylaniline (3.0 g, 22.19 mmol) in ethyl acetate (22 mL) cooled in an ice bath were added sequentially sodium bicarbonate (3.73 g, 44.4 mmol) and chloroacetyl chloride (2.1 mL, 26.6 mmol) dropwise over four minutes. After stirring in the ice bath for ten minutes, the reaction mixture was warmed to room temperature and stirred for 90 minutes. Water (15 mL) was added to the reaction mixture, and the phases were separated. The organic layer was washed with brine (20 mL), dried over magnesium sulfate, filtered, and concentrated to afford the title compound as a dark solid (4.9 g, 94%): 1H NMR (400 MHz, CDCl3) δ 8.32 (s, 1H), 7.82-7.75 (m, 1H), 7.35-7.29 (m, 1H), 7.25-7.21 (m, 2H), 4.26 (s, 2H), 3.04 (hept, J=6.9 Hz, 1H), 1.28 (d, J=6.8 Hz, 6H); 13C NMR (126 MHz, CDCl3) δ 164.06, 140.06, 133.10, 126.57, 126.50, 125.77, 123.78, 43.21, 28.12, 22.87; IR (thin film) 3255, 2963, 2869, 1662, 1525 cm-1.
91%	With acetic acid for 1.5h;
	In acetic acid cooling;

With triethylamine In dichloromethane at 20℃;

Reference： [1]Current Patent Assignee: CORTEVA INC - US2018/99958, 2018, A1 Location in patent: Paragraph 0247-0249
[2]Soyer, Zeynep; Kilic, Fatma Sultan; Erol, Kevser; Pabuccuoglu, Varol [Il Farmaco, 2004, vol. 59, # 8, p. 595 - 600]
[3]Soyer, Zeynep; Kilic, Fatma Sultan; Erol, Kevser; Pabuccuoglu, Varol [Archiv der Pharmazie, 2004, vol. 337, # 2, p. 105 - 111]
[4]Lee, Jae Wook; Hirota, Tsuyoshi; Kumar, Anupriya; Kim, Nam-Jung; Irle, Stephan; Kay, Steve A. [ChemMedChem, 2015, vol. 10, # 9, p. 1489 - 1497]

13
[ 57-71-6 ]
[ 643-28-7 ]
[ 639792-80-6 ]

Reference： [1]European Journal of Inorganic Chemistry,2003,p. 2683 - 2692

14
[ 643-28-7 ]
[ 132475-93-5 ]

Yield	Reaction Conditions	Operation in experiment
81%	With sulfuric acid; nitric acid; at 0℃;Cooling with ice;	Example 1; Synthesis of target compound 1a (NEt-3IP) The scheme of production method in this Example will be shown in Figure 1.1) Synthesis of Intermediate A 2- isopropyl aniline (2.7 g, 20.0 mmol) and concentrated sulfuric acid (5 mL) were mixed under cooling in an ice bath, and then mixed acid (concentrated nitric acid : concentrated sulfuric acid = 2 : 5, 7 mL) was added while not allowing the temperature to increase beyond 0C. Then, the completion of the reaction was confirmed on TLC (Thin Layer Chromatography) plates (ethyl acetate : n-hexane = 1 : 2). After neutralization was performed by using 2 N aqueous sodium hydroxide, the resultant solution was extracted with ethyl acetate (70 mL × 3). Organic layer was washed with water (100 mL × 2) and saturated saline solution (50 mL). After the obtained organic layer was dried using magnesium sulfate, the solvent was distilled off under reduced pressure to yield dark orange oil of Intermediate A (2.9 g, 81%). 1H NMR (500 MHz, CDCl3) delta 7.60 (dd, 1 H, J = 8.5 Hz and 2.5 Hz, Ar-H), 7.50 (d, 1 H, J = 2.5 Hz, Ar-H), 7.24 (d, 1 H, J = 8.5 Hz, Ar-H), 3.95 (br s, 2 H, NH2), 2.90 (sept, 1 H, J= 7.0 Hz, CH(CH3)2), 1.29 (d, 6 H, J = 7.0 Hz, CH(CH3)2).
16%		Example 45 Synthesis of 2-isopropyl-5-nitroaniline 70% HNO3 (5.1 mL, 84.76 mmol, 1.2 equiv) was added dropwise to a mixture of 2-isopropylaniline (10 mL, 9.55 g, 70.63 mmol, 1 equiv) in 70 mL of conc. sulfuric acid at 0 C. The reaction mixture was stirred at this temperature for 30 minutes and then poured onto ice. The aqueous mixture was extracted with EtOAc (2*150 mL). The organic layers were combined and washed with sat'd NaHCO3. After evaporation, the residue was purified by column chromatography on silica gel using EtOAc/hexanes (3/7) to give 2 g of product (16%) as a dark red oil. 1H NMR (CDCl3, 300 MHz): delta 7.60 (dd, J=8.1, 2.7 Hz, 1H), 7.50 (d, J=2.7 Hz, 1H), 7.23 (d, J=8.7 Hz, 1H), 2.91 (sept, J=6.6 Hz, 1H), 1.28 (d, J=6.9 Hz, 6H); m/z=181 (M+H)+.
		2-Isopropylaniline (1.0 g, 0.0074 mol) was dissolved in Sulfuric acid (10.0 mL, 0.188 mol) at -5 0C. Potassium nitrate (0.75 g, 0.0074 mol) was then added keeping the temperature below 0 0C. The reaction was then allowed to stir gradually warming to room temperature until HPLC showed consumption of starting material. The mixture was then poured over water and the solid product was collected via filtration. The filtrate was then neutralized with 2M sodium hydroxide and the product was extracted with ethyl acetate. Combined organic extracts were dried over sodium sulfate, filtered and reduced to afford 1.10 grams of 2-Isopropyl-5-nitro- phenylamine. 1H NMR (400 MHz, DMSO, d6) delta 7.56 (s, IH), 7.46 (dd, IH, J = 2.40, 6.04 Hz), 7.30 (d, IH, J = 8.52 Hz), 5.63 (s, 2H), 3.05 (sept, IH, J = 6.76 Hz), 1.17 (d, 6H, J = 6.76 Hz).

Reference： [1]European Journal of Organic Chemistry,2009,p. 687 - 698
[2]Patent: EP2116523,2009,A1 .Location in patent: Page/Page column 13; 34
[3]Patent: US2012/22092,2012,A1 .Location in patent: Page/Page column 45
[4]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 668 - 671
[5]Patent: WO2010/71885,2010,A1 .Location in patent: Page/Page column 452-453

15
[ 7073-94-1 ]
[ 64653-45-8 ]
[ 643-28-7 ]

Yield	Reaction Conditions	Operation in experiment
89%	Stage #1: 1-bromo-2-isopropylbenzene With ammonia; sodium t-butanolate In 1,2-dimethoxyethane at 90℃; for 20h; Stage #2: With hydrogenchloride In 1,2-dimethoxyethane; water Stage #3: With sodium hydrogencarbonate In 1,2-dimethoxyethane; water	7 l-Bromo-2-/-propylbenzene (0.199 g, 1.00 mmol), (CyPF-t-Bu)PdCl2 (7.30 mg, 1.00 x 10"2 mmol), and NaOtBu (0.192 g, 2.00 mmol) in 4.0 mL DME gave 0.120 g (89%) of 2-r-propylaniIine as a solid (hexane/ethyl acetate: 70/30). 1H NMR (CDCl3) δ 7.08 (dd, J= 6.0, 1.2 Hz, 1 H), 6.96 (td, J= 6.0, 1.2 Hz, 1 H), 6.73 (td, J = 6.0, 0.8 Hz, 1 H)5 6.60 (dd, J= 6.0, 1.2 Hz, 1 H), 3.56 (s, br, 2 H), 2.83 (sept, J= 5.2 Hz, 1 H), 1.20 (J= 5.2 Hz, 6 H); 13C NMR (CDCl3) δ 143.22, 132.55, 126.44, 125.30, 118.92, 115.74, 27.56, 22.20.
81%	Stage #1: 1-bromo-2-isopropylbenzene With lithium amide In 1,2-dimethoxyethane at 90℃; for 24h; Sealed vial; Stage #2: With hydrogenchloride In 1,2-dimethoxyethane; water at 20℃; for 0.0833333h; Stage #3: With sodium hydrogencarbonate In 1,2-dimethoxyethane; water	16; 17 l-Bromo-2-/-propylbenzene (0.199 g, 1.00 mmol), (CyPF-Z-Bu)PdCl2 (7.30 mg, 1.00 x lO'2 mmol), and LiNH2 (0.230 g, 10.0 mmol) in 2.0 mL DME gave 0.109 g (81%) of 2-/-Propylaniline as a solid; Bromo-2-/-propylbenzene (1.99 g, 100 mmol) were weighed into a 100 mL round bottom flask with a stirring bar. DME (20.0 mL) was then added. The flask was sealed with a cap and wrapped tightly with electrical tape. The reaction mixture was stirred for 24 h at 90 0C. The reaction mixture was allowed to cool to room temperature before pouring into ice water (50.0 mL). To this mixture was added aqueous HCl (100 mL, 1.0 M). The mixture was stirred at room temperature for 5 min and was then neutralized with a saturated solution of NaHCO3 (50.0 mL). After extraction with CH2Cl2 (3 x 50.0 mL), the organic layer was separated and dried over MgSO4. The solvent was evaporated, and the crude product isolated by column chromatography, eluting with hexane/ethyl acetate (70/30) to give 1.11 g (82%) of 2-/-ρropylaniline as a solid.

Reference： [1]Current Patent Assignee: YALE UNIVERSITY - WO2007/109365, 2007, A2 Location in patent: Page/Page column 44; 45; 47
[2]Current Patent Assignee: YALE UNIVERSITY - WO2007/109365, 2007, A2 Location in patent: Page/Page column 48-49; 51-52

16
[ 108-86-1 ]
[ 643-28-7 ]
[ 38158-59-7 ]

Yield	Reaction Conditions	Operation in experiment
90%	With dicyclohexyl(2-methoxy-6-methylbiphenyl-2<SUP>,</SUP>-yl)phosphine; potassium <i>tert</i>-butylate; palladium diacetate In 1,4-dioxane at 160℃; for 0.166667h; Inert atmosphere; Microwave irradiation;
79%	With sodium t-butanolate In toluene at 100℃; for 24h;
73%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; sodium t-butanolate In toluene at 100℃; for 16h; Inert atmosphere;

With C₂₂H₂₆Cl₂NPPd; sodium t-butanolate In toluene at 110℃; for 22h; Inert atmosphere;

4.2.1 Aryl amination general procedures General procedure: Under a nitrogen atmosphere, an 8-mL vial was charged with NaOtBu (135 mg, 1.40 mmol), toluene (2 mL), aryl halide (1.0 mmol), amine (1.2 mmol) and (3IP)PdCl2 (5.6 mg, 11 μmol, 1.1 mol%). For the lower boiling amines (as noted in the data tables), 8 mL of toluene was used in order to minimize headspace within the vial. The reaction mixture was stirred and heated at 110 °C for 22 h. An aliquot of the resulting mixture was diluted with diethyl ether (1.8 mL), filtered through an alumina column and analyzed by gas chromatography. Bulk products were then isolated via column chromatography (silica; 10% ethyl acetate in pentane, unless otherwise noted) and further characterized by 1H and 13C NMR spectroscopy, as well as high-resolution mass spectrometry.

Reference： [1]Singh, Chandani; Rathod, Jayant; Jha, Vishwajeet; Panossian, Armen; Kumar, Pradeep; Leroux, Frédéric R. [European Journal of Organic Chemistry, 2015, vol. 2015, # 29, p. 6515 - 6525]
[2]Matsubara, Kouki; Ueno, Keita; Koga, Yuji; Hara, Kenji [Journal of Organic Chemistry, 2007, vol. 72, # 14, p. 5069 - 5076]
[3]Ward, Jonathan S.; Nobuyasu, Roberto S.; Batsanov, Andrei S.; Data, Przemyslaw; Monkman, Andrew P.; Dias, Fernando B.; Bryce, Martin R. [Chemical Communications, 2016, vol. 52, # 12, p. 2612 - 2615]
[4]Samblanet, Danielle C.; Schmidt, Joseph A. R. [Journal of Organometallic Chemistry, 2012, vol. 720, p. 7 - 18,12]

17
[ 463-71-8 ]
[ 643-28-7 ]
[ 36176-31-5 ]

Yield	Reaction Conditions	Operation in experiment
99%	With triethylamine In dichloromethane at 20℃; for 1h;
99%	In diethyl ether at 0 - 20℃; for 1.16667h;	1.2 Reference Example 1-2 Preparation of (2-isopropylphenyl)isothiocyanate (Compound 2). To a solution of 2-isopropylaniline (1.81 g) in diethylether (20 ml) was added dropwise thiophosgene (1.54 g) under ice-cooling for 10 min. The reaction mixture was stirred at room temperature for 1 h. To the reaction mixture was added water (30 ml). The reaction mixture was extracted with diethylether (60 ml), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give (2-isopropylphenyl)isothiocyanate (2.35 g, yield: 99 %) as a brown oil.
	With triethylamine In dichloromethane at 20℃; for 1h;

In diethyl ether; water

R.1.2 Reference Example 1-2 Reference Example 1-2 Preparation of (2-isopropylphenyl)isothiocyanate (Compound 2). To a solution of 2-isopropylaniline (1.81 g) in diethylether (20 ml) was added dropwise under ice-cooling for 10 minutes thiophosgene (1.54 g). The mixture was stirred at room temperature for 1 hour. To the reaction solution was added water (30 ml). The mixture was extracted with diethylether (60 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give (2-isopropylphenyl)isothiocyanate (2.35 g, yield: 99 %) as brown oil.

Reference： [1]Kai, Hiroyuki; Morioka, Yasuhide; Murashi, Takami; Morita, Koichi; Shinonome, Satomi; Nakazato, Hitoshi; Kawamoto, Keiko; Hanasaki, Kohji; Takahashi, Fumiyo; Mihara, Shin-ichi; Arai, Tohko; Abe, Kohji; Okabe, Hiroshi; Baba, Takahiko; Yoshikawa, Takayoshi; Takenaka, Hideyuki [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 14, p. 4030 - 4034]
[2]Current Patent Assignee: SHIONOGI & CO., LTD. - EP1375489, 2004, A1 Location in patent: Page 13
[3]Kai, Hiroyuki; Morioka, Yasuhide; Tomida, Minoru; Takahashi, Tadashi; Hattori, Maki; Hanasaki, Kohji; Koike, Katsumi; Chiba, Hiroki; Shinohara, Shunji; Kanemasa, Toshiyuki; Iwamoto, Yuka; Takahashi, Kohji; Yamaguchi, Yoshitaka; Baba, Takahiko; Yoshikawa, Takayoshi; Takenaka, Hideyuki [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 14, p. 3925 - 3929]
[4]Current Patent Assignee: SHIONOGI & CO., LTD. - EP1219612, 2002, A1

18
[ 201230-82-2 ]
[ 52562-19-3 ]
[ 19343-78-3 ]
[ 643-28-7 ]

Reference： [1]Chemical Communications,2007,p. 2710 - 2711

19
[ 643-28-7 ]
[ 60515-72-2 ]

Reference： [1]Gazzetta Chimica Italiana,1886,vol. 16,p. 114
[2]Patent: WO2008/62182,2008,A1

20
[ 643-28-7 ]
[ 2438-04-2 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1960,vol. 79,p. 1211 - 1222

21
[ 115951-16-1 ]
[ 643-28-7 ]
[ 672961-24-9 ]

Yield	Reaction Conditions	Operation in experiment
63%	With 1-methyl-1H-imidazole; diethyl cyanophosphonate;	1-TERT] butylcarbamoyl-1- [N- (2-isopropylphenyl)-cyclohexane carboxamide was isolated as a white solid (295.5mg, 63%) from 1-(Tert-butoxycarbonylamino) [CYCLOHEXANECARBOXYLIC] acid (200. Omg, 0. [82MMOL),] [2-ISOPROPYLANILINE] (0.13mL, 0. [90MMOL),] DECP (0.19mL, 1. [23MMOL)] and 1-methylimidazole (0.13mL, 1. [64MOL).

Reference： [1]Patent: WO2004/22534,2004,A1 .Location in patent: Page 119

22
[ 4755-77-5 ]
[ 643-28-7 ]
[ 42022-52-6 ]

Yield	Reaction Conditions	Operation in experiment
98%	With pyridine In dichloromethane at 0 - 25℃; for 16h;
85.8%	With triethylamine In dichloromethane at 0 - 20℃;	4.1 Preparation of Example 4; STEP 1 Ethyl oxalyl chloride (5 g, 0.037 mol) in 10 ml CH2CL2 was added dropwise to a solution of 2- isopropyl-aniline (4.37 g, 0.032 mol) and triethylamine (3.71 g, 0.037 mol) in 25 ml CH2CL2 at 0°C with stirring. The mixture was stirred at room temperature overnight and washed with 2N HCI, saturated NAHC03 and brine, and then the organic phase was dried over anhydrous NA2S04. The solvent was evaporated and 6. 51G of oxalic acid ethyl ester 2-isopropyl-anilide as a light brown oil were obtained (yield of 85.8%).
	With triethylamine In tetrahydrofuran at 0 - 20℃; Inert atmosphere;	Ethyl 2-(4-chloro-3-fluorophenylamino)-2-oxoacetate. General procedure: To a solution containing para-chloro-meta-fluoroaniline (10.0 g, 70.1 mmol) in 600 mL THF at 0 °C was added Et3N (9.11 mL, 70.1 mmol) followed by ethyl oxalylchloride (7.70 mL, 70.1 mmol) dropwise over 15 minutes. The reaction mixture was warmed to room temperature and stirred for 18 hrs. The reaction mixture was filtered and the filter cake was washed with one-300 mL portion of ethyl acetate. The organic phase was washed with two-100 mL portions of 1M HCl, dried over MgSO4, filtered, and concentrated to give the product. Recrystallization from hot Et2O gave 14.4 g (84%) of 27 as a colorless crystalline solid.

Reference： [1]Kong, Lingyu; Chou, Yajie; Jean, Marion; Albalat, Muriel; Vanthuyne, Nicolas; Nava, Paola; Humbel, Stéphane; Clavier, Hervé [Advanced Synthesis and Catalysis, 2021, vol. 363, # 17, p. 4229 - 4238]
[2]Current Patent Assignee: BAYER AG; LUBOS ERDELEN ANGELIKA HF - WO2004/101532, 2004, A1 Location in patent: Page 15
[3]Lalonde, Judith M.; Elban, Mark A.; Courter, Joel R.; Sugawara, Akihiro; Soeta, Takahiro; Madani, Navid; Princiotto, Amy M.; Kwon, Young Do; Kwong, Peter D.; Schön, Arne; Freire, Ernesto; Sodroski, Joseph; Smith III, Amos B. [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 1, p. 91 - 101]

23
[ 75-15-0 ]
[ 643-28-7 ]
[ 36176-31-5 ]

Yield	Reaction Conditions	Operation in experiment
99%	Stage #1: carbon disulfide; 2-isopropylaniline With triethylamine In toluene at 20℃; for 13h; Stage #2: With chloroformic acid ethyl ester; triethylamine In dichloromethane at 0 - 20℃; for 1.16667h;	1.1 Reference Example 1-1 Preparation of (2-isopropylphenyl)isothiocyanate (Compound 2). To a mixture of 2-isopropylaniline (5.00 g), triethylamine (3.74 g) and toluene (10 ml) was added dropwise for 10 min carbon dioxide (2.81 g). The reaction mixture was stirred at room temperature for 1 h and kept stationary for 12 h. The reaction mixture was concentrated under reduced pressure. Dichloromethane (20 ml) and triethylamine (3.74 g) were added thereto. To the reaction mixture was added ethyl chlorocarbonate (4.01 g) under ice-cooling for 10 min. The reaction mixture was stirred at room temperature for 1 h. To the reaction mixture was added 10% hydrochloric acid (20 ml). The reaction mixture was extracted with dichloromethane (60 ml), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give (2-isopropylphenyl)isothiocyanate (6.55 g, yield: 99 %) as a yellow oil.1H-NMR, (δ ppm TMS / CDCl3 ) 1.25(6H, d, J=6.7), 3.25(1H, q, J=6.7), 7.14-7.30(4H, m).

Reference： [1]Current Patent Assignee: SHIONOGI & CO., LTD. - EP1375489, 2004, A1 Location in patent: Page 13

24
[ 5955-72-6 ]
[ 643-28-7 ]
[ 1056619-15-8 ]

Yield	Reaction Conditions	Operation in experiment
	In 1-methyl-pyrrolidin-2-one; at 150℃; for 1h;Microwave irradiation;	Example 84; Synthesis of lH-indazole-6-carboxylic acid [2-(2-isopropylphenylamino)-3H-benzimidazol- 5-yl]-amideTo a solution of 2-chloro-5-nitro-lH-benzimidazole (1.5 mmol; prepared from nitration of 2-chloro-lH-benzimidazole; GaIy et al, J. Heterocycl. Chem. 1997, 34, 6, 1781- 1788) in dry NMP (3 mL) was added 2-isopropylaniline (4 mmol). The resulting solution was subjected to microwave irradiation at 150 0C for Ih. The contents were cooled to room temperature, diluted with water (20 mL) and extracted with EtOAc (2x15 mL). The combined extracts were then washed with water (20 mL) and brine (20 mL) and dried over anhydrous sodium sulfate. The solvent was removed in vacuo and the residue obtained was purified by silica gel chromatography using EtOAc/hexane as eluent to obtain (2- isopropylphenyl)-(5-nitro-lH-benzimidazol-2-yl)-amine as light yellow solid.The nitro compound (1 mmol) as above was reduced under hydrogenation conditions as described in general procedure F to afford lambda/"2-(2-isopropylphenyl)-lH-benzimidazole-2,5- diamine. Methyl Indazole-6-carboxylate (4 mmol; Batt el al, J. Med. Chem. 2000, 43, 41-58) was hydrolyzed as in general procedure C to obtain leta-Indazole-6-carboxylic acid. The <n="70"/>carboxylic acid (0.5 tnmol) was coupled with aforementioned N -(2-isopropylphenyl)-l H- benzimidazole-2,5-diamine (0.5 mmol) using HBTU as described in general procedure D to yield lH-indazole-6-carboxylic acid [2-(2-isopropylphenylamino)-3H-benzimidazol-5-yl]- amide as an off-white solid. MS: m/z 411 (M+H) .

Reference： [1]Patent: WO2007/95124,2007,A2 .Location in patent: Page/Page column 67-68

25
[ 614-76-6 ]
[ 643-28-7 ]
[ 959855-35-7 ]

Yield	Reaction Conditions	Operation in experiment
86%	With potassium phosphate In <i>tert</i>-butyl alcohol at 110℃; for 18h;

Reference： [1]Zheng, Nan; Anderson, Kevin W.; Huang, Xiaohua; Nguyen, Hanh Nho; Buchwald, Stephen L. [Angewandte Chemie - International Edition, 2007, vol. 46, # 39, p. 7509 - 7512]

26
[ 643-28-7 ]
[ 81090-34-8 ]

Yield	Reaction Conditions	Operation in experiment
94%	With 1,3-di-n-butyl-1H-imidazol-3-ium tribromide at 20℃; Neat (no solvent); regioselective reaction;
81%	With N-Bromosuccinimide; ammonium acetate In acetonitrile at 20℃; for 0.166667h;	4-Bromo-2-isopropylaniline (2)¹⁴ To a solution of 2-isopropylaniline (2.70 g, 2.83 mL, 20 mmol) and NH4OAc (154 mg, 2 mmol) in MeCN (100 mL) was added NBS (3.74 g, 21 mmol). The mixture was stirred at r.t. for 10 min followed by concentration in vacuo. After addition of H2O (100 mL) and extraction with EtOAc (3 × 100 mL), the combined organic layers were dried (MgSO4), evaporated, and the residue was purified by flash column chromatography (cyclohexane-EtOAc, 10:1) to give 2 (3.45 g, 81%) as a brown oil. 1H NMR (360 MHz, CDCl3): δ = 1.17 (d, J = 6.8 Hz, 6 H), 2.77 (hept, J = 6.8 Hz, 1 H), 3.56 (br s, 2 H), 6.48 (d, J = 8.4 Hz, 1 H), 7.03 (dd, J = 8.4, 2.3 Hz, 1 H), 7.14 (d, J = 2.3 Hz, 1 H). MS (APCI): m/z = 213.9 [M + H]+, 215.9 [M + H]+.
81%	With N-Bromosuccinimide; ammonium acetate In acetonitrile at 20℃; for 0.166667h;	1 4-Bromo-2-isopropylaniline (2) To a solution of 2-isopropylaniline (2.70 g, 2.83 mL, 20 mmol) and NH4OAc (154 mg, 2 mmol) in acetonitrile (100 mL) was added N-bromosuccinimide (3.74 g, 21 mmol). The mixture was stirred at room temperature for 10 min followed by concentration in vacuo. After addition of H2O and extraction with ethyl acetate, the organic layer was dried (MgSO4), evaporated and the residue was purified by flash column chromatography (cyclohexane/ethyl acetate 10:1) to give 2 (3.45 g, 81%) as a brown oil. 1H NMR (360 MHz, CDCl3): δ = 1.17 (d, J = 6.8 Hz, 6 H), 2.77 (hept, J = 6.8Hz, 1 H), 3.56 (br s, 2 H), 6.48 (d, J = 8.4 Hz, 1 H), 7.03 (dd, J = 8.4, 2.3 Hz, 1 H), 7.14 (d, J = 2.3 Hz, 1 H). MS (APCI): m/z 213.9 [M + H]+ and 215.9 [M + H]+.

75%	With 1-butyl-3-methylpyridinium tribromide at 20℃; for 0.0666667h;
75%	With N-Bromosuccinimide; ammonium acetate In acetonitrile at 20℃; for 0.166667h;
57%	With bromine In dichloromethane at -50℃; for 1.33333h; Cooling with acetone-dry ice;	7.a To a cooled solution of 2-iso-propyl aniline (714 mg, 5.28 mmol) in dichloromethane (20 mL) at -50° C. in a dry ice/acetone bath was added a solution of bromine (269 μl, 5.28 mmol) in dichloromethane (5 mL) over 20 min. After completion of the addition, the reaction mixture was stirred for an additional hour. Purification by column chromatography (silica gel, hexane/ethyl acetate) gave 4-bromo-2-iso-propyl-phenylamine as a brown oil (1.53 g, 57%); 1H NMR (300 MHz, DMSO-d6): δ 7.01 (m, 2H), 6.55 (d, 1H, J=13 Hz), 5.05 (bs, 2H), 2.92 (m, 1H), 1.11 (d, 6H, J=7 Hz); TLC conditions: Uniplate silica gel, 250 microns; Mobile phase=Hexane/ethyl acetate [10:1]; Rf=0.11
57%	With bromine In dichloromethane at -50℃; for 0.333333h;	7.b.a To a cooled solution of 2-iso-propyl aniline (714 mg, 5. 28 mmol) in dichloromethane (20 mL) at-50 C in a dry ice/acetone bath was added a solution of bromine(269, ul, 5. 28 mmol) in dichloromethane (5 mL) over 20 min. After completion of the addition, the reaction mixture was stirred for an additional hour. Purification by column chromatography (silica gel, hexane/ethyl acetate) gave 4-bromo-2-iso-propyl- phenylamine as a brown oil (1.53 g, 57%) ; 1H NMR (300 MHz, DMSO-d6) :6 7.01 (m, 2H), 6.55 (d,1H, J= 13 Hz), 5.05 (bs, 2H), 2.92 (m,1H), 1.1 l (d, 6H, J= 7 Hz); TLC conditions: Uniplate silica gel, 250 microns; Mobile phase = Hexane/ethyl acetate [10: 1];Rf=0. 11
53%	With N-Bromosuccinimide; ammonium acetate In acetonitrile at 25℃; for 1h;
50%	With N-Bromosuccinimide; ammonium acetate In acetonitrile at 20℃; for 0.166667h;
22%	With bromine In chloroform for 1h; Inert atmosphere;

Reference： [1]Location in patent: experimental part Borikar, Sanjay P.; Daniel, Thomas; Paul, Vincent [Synthetic Communications, 2010, vol. 40, # 5, p. 647 - 653]
[2]Lang, Christopher; Gmeiner, Peter [Synthesis, 2013, vol. 45, # 17, p. 2474 - 2480]
[3]Current Patent Assignee: FRIEDRICH-ALEXANDER-UNIVERSITÄT ERLANGEN-NÜRNBERG - EP3279197, 2018, A1 Location in patent: Paragraph 0124; 0126
[4]Location in patent: scheme or table Borikar, Sanjay P.; Daniel, Thomas; Paul, Vincent [Tetrahedron Letters, 2009, vol. 50, # 9, p. 1007 - 1009]
[5]Trobe, Melanie; Blesl, Julia; Vareka, Martin; Schreiner, Till; Breinbauer, Rolf [European Journal of Organic Chemistry, 2022, vol. 2022, # 17]
[6]Current Patent Assignee: LIGAND PHARMACEUTICALS INC - US2009/28925, 2009, A1 Location in patent: Page/Page column 103
[7]Current Patent Assignee: LIGAND PHARMACEUTICALS INC - WO2005/51298, 2005, A2 Location in patent: Page/Page column 237
[8]Joseph, Roymon; Masson, Eric [Organic and Biomolecular Chemistry, 2013, vol. 11, # 19, p. 3116 - 3127]
[9]Chiellini, Grazia; Nesi, Giulia; Sestito, Simona; Chiarugi, Sara; Runfola, Massimiliano; Espinoza, Stefano; Sabatini, Martina; Bellusci, Lorenza; Laurino, Annunziatina; Cichero, Elena; Gainetdinov, Raul R.; Fossa, Paola; Raimondi, Laura; Zucchi, Riccardo; Rapposelli, Simona [Journal of Medicinal Chemistry, 2016, vol. 59, # 21, p. 9825 - 9836]
[10]Wink, Christoph; Detert, Heiner [Journal of Physical Organic Chemistry, 2013, vol. 26, # 2, p. 144 - 150]

27
[ 4403-36-5 ]
[ 643-28-7 ]
[ 1004290-11-2 ]

Reference： [1]Archiv der Pharmazie,2007,vol. 340,p. 656 - 660

28
[ 643-28-7 ]
[ 67083-38-9 ]

Yield	Reaction Conditions	Operation in experiment
60%	With Oxone In dichloromethane; water at 20℃; Inert atmosphere;
	With 3-chloro-benzenecarboperoxoic acid
	With Oxone Inert atmosphere;

	With Oxone In dichloromethane; water
	With potassium peroxymonosulfate sulfate In dichloromethane; water at 20℃; for 4h;
	With oxone\|\|potassium monopersulfate triple salt; water In dichloromethane at 20℃;

Reference： [1]Ran, Rui-Qiao; Xiu, Shi-Dong; Li, Chuan-Ying [Organic Letters, 2014, vol. 16, # 24, p. 6394 - 6396]
[2]Location in patent: scheme or table Ma, Yajun; Wei, Siping; Lan, Jingbo; Wang, Jingzhi; Xie, Rugang; You, Jingsong [Journal of Organic Chemistry, 2008, vol. 73, # 21, p. 8256 - 8264]
[3]Yanagisawa, Akira; Lin, Yuqin; Takeishi, Akihiro; Yoshida, Kazuhiro [European Journal of Organic Chemistry, 2016, vol. 2016, # 32, p. 5355 - 5359]
[4]Roscales, Silvia; Csákÿ, Aurelio G. [Organic Letters, 2018, vol. 20, # 6, p. 1667 - 1671]
[5]Teders, Michael; Pogodaev, Aleksandr A.; Bojanov, Glenn; Huck, Wilhelm T. S. [Journal of the American Chemical Society, 2021, vol. 143, # 15, p. 5709 - 5716]
[6]An, Qian-Jin; Xia, Wang; Ding, Wei-Yi; Liu, Huan-Huan; Xiang, Shao-Hua; Wang, Yong-Bin; Zhong, Guofu; Tan, Bin [Angewandte Chemie - International Edition, 2021, vol. 60, # 47, p. 24888 - 24893][Angew. Chem., 2021, vol. 133, # 47, p. 25092 - 25097]

29
[ 25991-27-9 ]
[ 643-28-7 ]
[ 1195782-78-5 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: methyl 2-oxo-2H-pyrane-3-carboxylate; 2-isopropylaniline In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; Stage #2: With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran; N,N-dimethyl-formamide at 20℃;	54 Methyl 2-oxo-2H-pyran-3-carboxylate (3.0 g, 19 mmol) was dissolved in a mixed solvent of tetrahydrofuran (40 mL) and N, N-dimethylformamide (10 mL) , and 2- ( 1-methylethyl) aniline (2.7 mL, 19 mmol) was added. After stirring overnight at room temperature, l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (4.5 g, 23 mmol) and 4- (N, N- dimethylamino) pyridine (120 mg, 1.0 mmol) were added, and the mixture was further stirred overnight at room temperature. The reaction system was diluted with ethyl acetate and washed with saturated aqueous sodium hydrogen carbonate solution, and the organic layer was dried over sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=40/60->60/40) to give methyl l-[2-(l- methylethyl) phenyl] -2-oxo-l, 2-dihydropyridine-3-carboxylate (800 mg) . Methyl 1- [2- (1-methylethyl) phenyl] -2-oxo-l, 2- dihydropyridine-3-carboxylate (800 mg) was dissolved in a mixed solvent of tetrahydrofuran (5 mL) and methanol (5 mL) , IN aqueous sodium hydroxide solution (5 mL) was added, and the mixture was stirred at room temperature for 2 hr. The mixture was diluted with distilled water (20 mL) and washed with ethyl acetate. The aqueous layer was acidified with IN hydrochloric acid (7 mL) and extracted twice with ethyl acetate. The collected organic layer was dried over sodium sulfate, and the solvent was evaporated under reduced pressure. A small amount of hexane/ethyl acetate was added to the residue, and the resulting precipitate was collected by filtration to give 1- [2- ( 1-methylethyl) phenyl] -2-oxo-l, 2-dihydropyridine-3- carboxylic acid (760 mg, 15%) as a white solid.1H-NMR (DMSOd6, 300 MHz) δ 1.07 - 1.18 (6H, m) , 2.51 - 2.57 (IH, m) , 6.76 - 6.87 (IH, m) , 7.32 - 7.43 (2H, m) , 7.50 - 7.62 (2H, m) , 8.19 (IH, dd, J = 6.6, 2.1 Hz), 8.53 (IH, dd, J = 7.2, 2.1 Hz) , 14.25 (IH, s) .

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2009/136663, 2009, A1 Location in patent: Page/Page column 167-168

30
[ 164148-92-9 ]
[ 32315-10-9 ]
[ 643-28-7 ]
[ 1190074-19-1 ]

Yield	Reaction Conditions	Operation in experiment
81%		To a dichloromethane (10 mL) solution of triphosgene (474 mg), a dichloromethane (10 mL) solution of 2-isopropylaniline (540 mg) and triethylamine (1.2 mL) was gradually added at room temperature. After 2 hours, a dichloromethane (10 mL) solution of 6-amino-2N-Boc-1,2,3,4-tetrahydroisoquinoline (993 mg) and triethylamine (1.2 mL) was added thereto. The reaction mixture was stirred for 30 minutes and concentrated. The residue was purified by chromatography (dichloromethane/ethyl acetate) to obtain the title compound (1.32 g, 81%) as an off-white solid. 1H NMR (400 MHz, CDCl3): delta (ppm) = 7.43-7.38 (2H, m), 7.33-7.27 (3H, m), 7.16 (1H, brs), 7.02 (1H, d, J = 7.8 Hz), 6.35 (1H, s), 6.18 (1H, s), 4.51 (2H, s), 3.61 (2H, t, J = 5.5 Hz), 3.25-3.18 (1H, m), 2.79 (2H, t, J = 5.9 Hz), 1.49 (9H, s), 1.22 (6H, d, J = 6.7 Hz).

Reference： [1]Patent: EP2256105,2010,A1 .Location in patent: Page/Page column 43

31
[ 109-04-6 ]
[ 643-28-7 ]
[ 1262533-45-8 ]

Yield	Reaction Conditions	Operation in experiment
82%	for 12h; Inert atmosphere; Reflux;
	With C₂₂H₂₆Cl₂NPPd; sodium t-butanolate In toluene at 110℃; for 22h; Inert atmosphere;	4.2.1 Aryl amination general procedures General procedure: Under a nitrogen atmosphere, an 8-mL vial was charged with NaOtBu (135 mg, 1.40 mmol), toluene (2 mL), aryl halide (1.0 mmol), amine (1.2 mmol) and (3IP)PdCl2 (5.6 mg, 11 μmol, 1.1 mol%). For the lower boiling amines (as noted in the data tables), 8 mL of toluene was used in order to minimize headspace within the vial. The reaction mixture was stirred and heated at 110 °C for 22 h. An aliquot of the resulting mixture was diluted with diethyl ether (1.8 mL), filtered through an alumina column and analyzed by gas chromatography. Bulk products were then isolated via column chromatography (silica; 10% ethyl acetate in pentane, unless otherwise noted) and further characterized by 1H and 13C NMR spectroscopy, as well as high-resolution mass spectrometry.
172 mg	With palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene at 80℃; for 3h;

Reference： [1]Location in patent: experimental part Allen, John J.; Hamilton, Christopher E.; Barron, Andrew R. [Dalton Transactions, 2010, vol. 39, # 47, p. 11451 - 11468]
[2]Samblanet, Danielle C.; Schmidt, Joseph A. R. [Journal of Organometallic Chemistry, 2012, vol. 720, p. 7 - 18,12]
[3]Caytan, Elsa; Farran, Daniel; Furukawa, Gaku; Homma, Yuki; Kitagawa, Osamu; Roussel, Christian; Shirai, Takeshi; Vanthuyne, Nicolas [Journal of Organic Chemistry, 2020, vol. 85, # 7, p. 5109 - 5113]

32
[ 104-85-8 ]
[ 643-28-7 ]
[ 1313508-11-0 ]

Yield	Reaction Conditions	Operation in experiment
83%	Stage #1: 2-isopropylaniline With n-butyllithium In diethyl ether; pentane at 0 - 20℃; for 2h; Stage #2: para-methylbenzonitrile In diethyl ether; pentane at 20℃; for 1h;	2-isopropylaniline (5.0 mL, 36.1 mmol) was added to 100 mL of diethylether and cooled to 0 °C. Butyllithium (18.0 mL of 2.0 M solution in pentane, 36.1 mmol) was added dropwise to the cooled aniline solution, affording a light yellow suspension after complete addition. The slurry was warmed to room temperature and stirred for 2 hours. Toluonitrile (4.23 g, 36.1 mmol) was added slowly resulting in the formation of a bright yellow solution after complete addition. Stirring was continued for 1 hour and the solvent was removed in vacuo. Tetrahydrofuran (150 mL) was added and the mixture was refluxed overnight under argon, yielding a dark orange-brown solution. Distilled water (2.0 mL, 1 12 mmol) was added and the mixture became a milky yellow solution after stirring for 30 minutes at room temperature. Solid, presumably lithium hydroxide, was removed via aerobic filtration and the remaining solvent was removed in vacuo, to produce a light yellow solid. The solid was slurried in 50 mL of pentane and stirred for 2 hours. Filtration of the slurry yielded 7.56 g (83 %) of light yellow solid. lU NMR (400 MHz, CDC13): 7.77 (d, 2H), 7.30 (d, 1H), 7.22 (d, 2H), 7.15 (t, 1H), 7.04 (t, 1H), 6.83 (d, 1 H), 4.70 (s, 2H), 3.16 (septet, 1H), 2.40 (s, 3H), 1.19 (d, 6H).

Reference： [1]Current Patent Assignee: PHILLIPS 66; CHEVRON CORP - WO2011/82192, 2011, A1 Location in patent: Page/Page column 309-310

33
[ 643-28-7 ]
[ 2438-04-2 ]
[ 129976-23-4 ]

Reference： [1]Canadian Journal of Chemistry,1990,vol. 68,p. 1106 - 1115

34
[ 3282-30-2 ]
[ 643-28-7 ]
[ 448250-74-6 ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane at 20℃;
	With sodium hydrogencarbonate In dichloromethane at 20℃;	2.3. General procedure for synthesis of pivanilide substrates General procedure: To a solution of aromatic amine (8.3 mmol) and NaHCO3 (24.8 mmol) in DCM (30 mL) was added pivaloyl chloride (9.1 mmol) in a dropwise manner at room temperature. After completion of the reaction (3-4 h, TLC), the reaction mixture was diluted with DCM. The organic phase was then thoroughly washed with brine, dried over Na2SO4 then concentrated in vacuo to give the desired pivanilide
	With sodium hydrogencarbonate In dichloromethane at 20℃;

With tetra-(n-butyl)ammonium iodide; sodium hydroxide In dichloromethane; water at 0℃; for 0.166667h;

Reference： [1]Li, Yan; Li, Zhongshu; Xiong, Tao; Zhang, Qian; Zhang, Xiangyang [Organic Letters, 2012, vol. 14, # 13, p. 3522 - 3525]
[2]Yang, Hyun Ji; Mathew, Bijoy P.; Oh, Dong Gun; Myung, Kyungjae; Kwak, Ja Hun; Hong, Sung You [Catalysis Communications, 2017, vol. 90, p. 83 - 86]
[3]Mathew, Bijoy P.; Yang, Hyun Ji; Kim, Joohee; Lee, Jae Bin; Kim, Yun-Tae; Lee, Sungmin; Lee, Chang Young; Choe, Wonyoung; Myung, Kyungjae; Park, Jang-Ung; Hong, Sung You [Angewandte Chemie - International Edition, 2017, vol. 56, # 18, p. 5007 - 5011][Angew. Chem., 2017, vol. 129, # 18, p. 5089 - 5093]
[4]Sahoo, Manoj K.; Midya, Siba P.; Landge, Vinod G.; Balaraman, Ekambaram [Green Chemistry, 2017, vol. 19, # 9, p. 2111 - 2117]

35
[ 1003-31-2 ]
[ 643-28-7 ]
[ 1390632-82-2 ]

Reference： [1]Journal of the American Chemical Society,2012,vol. 134,p. 11980 - 11983

36
[ 1003-31-2 ]
[ 643-28-7 ]
[ 1390633-11-0 ]

Reference： [1]Journal of the American Chemical Society,2012,vol. 134,p. 11980 - 11983

37
[ 100-47-0 ]
[ 643-28-7 ]
[ 1272860-52-2 ]

Yield	Reaction Conditions	Operation in experiment
70%	With sodium hydride In dimethyl sulfoxide at 0 - 20℃;
69%	Stage #1: benzonitrile; 2-isopropylaniline at 20℃; for 0.25h; Stage #2: With aluminum (III) chloride at 140℃; for 15h; Sealed tube;	3.1. General procedure for the synthesis of N-substituted amidines General procedure: Amidines were synthesized according to slightly modifiedliterature procedures (Scheme 1) [25-27]. Aniline (6.0 mmol, 1.20eq) and a corresponding nitrile (5.0 mmol, 1 eq) were stirred for15 min at room temperature in the pressure tube (75 mL). Further,AlCl3 (5.0 mmol, 1.00 eq) was added in one portion, the tube wassealed, and the mixture was stirred at 140 °C for 15 h. Cold water(50 mL) was added. To the formed suspension, concentrated solutionof NaOHwas added till pH reached 14 (pHwas controlled usinga universal paper indicator). The aqueous layer was extracted withCHCl3 (3 x 30 mL). The combined organic layers were dried overNa2SO4, filtered and concentrated under reduced pressure. Theresidue was purified by double recrystallization from hexane or a mixture of hexane/ethyl acetate or using preparative column chromatography. Analytical data were in excellent agreement withthe previously reported.
	With sodium hydride In dimethyl sulfoxide; mineral oil at 0 - 20℃; Inert atmosphere;

Reference： [1]Wang, Yi-Feng; Chen, Hui; Zhu, Xu; Chiba, Shunsuke [Journal of the American Chemical Society, 2012, vol. 134, # 29, p. 11980 - 11983]
[2]Mikhaylov, Vladimir N.; Sorokoumov, Viktor N.; Novikov, Alexander S.; Melnik, Maria V.; Tskhovrebov, Alexander G.; Balova, Irina A. [Journal of Organometallic Chemistry, 2020, vol. 912]
[3]Lu, Guoqiang; Luo, Nan; Hu, Fangpeng; Ban, Zihui; Zhan, Zhenzhen; Huang, Guo-Sheng [Advanced Synthesis and Catalysis, 2020, vol. 362, # 3, p. 487 - 492]

38
[ 89787-12-2 ]
[ 643-28-7 ]

Reference： [1]Journal of Organic Chemistry,2015,vol. 80,p. 2545 - 2553
[2]Journal of the American Chemical Society,2012,vol. 134,p. 18253 - 18256

39
[ 1426137-47-4 ]
[ 643-28-7 ]
[ 1426137-29-2 ]

Yield	Reaction Conditions	Operation in experiment
67%	With lithium bromide In methanol at 20℃; for 12h;	Synthesis of aminoalcohol fused spirochromone conjugates (4-6) General procedure: To a stirred solution of epoxide 3a/3b/3c (0.5 mmol) and LiBr (0.1 mmol) in methanol (3 mL) was added an appropriate amine (0.55 mmol) and the resulting reaction mixture was stirred at rt for 12 h. After completion of the reaction (monitored by TLC), solvent was removed in vacuo and the reaction mixture was diluted with ethyl acetate (20 mL) and then washed with water (2 X 5 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo. The residue was purified by column chromatography over silica gel (ethyl acetate/ petroleum ether 3:7 (v/v)) afforded pure product 4-6.

Reference： [1]Mujahid; Gonnade; Yogeeswari; Sriram; Muthukrishnan [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 5, p. 1416 - 1419]

40
[ 643-28-7 ]
[ 1147014-97-8 ]

Reference： [1]Organic and Biomolecular Chemistry,2013,vol. 11,p. 3116 - 3127

41
[ 35150-09-5 ]
[ 643-28-7 ]
[ 1387882-10-1 ]

Reference： [1]Medicinal Chemistry Research,2013,vol. 22,p. 4708 - 4714

42
[ 4744-50-7 ]
[ 643-28-7 ]
[ 353785-50-9 ]

Reference： [1]Organic Letters,2013,vol. 15,p. 4806 - 4809

43
[ 109756-03-8 ]
[ 643-28-7 ]
C₁₉H₂₇NSi₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With lithium hexamethyldisilazane In tetrahydrofuran at 0℃; for 2h; Inert atmosphere;	General procedure: BSB-Cl 2 (314 mg, 1.2 mmol) and aniline 1 (1mmol) were premixed in THF (10 ml) at0 C to which was added LiHMDS (2 ml, 2 mmol). The resulting mixture was stirred for2 h at this temperature. Upon reaction completion, the solution was concentrated. Theresidue was purified with basic alumina flash chromatography to afford pure product

Reference： [1]Lu, Erhu; Yadav, Arun; Weaver, Donald F.; Reed, Mark A. [Synlett, 2013, vol. 24, # 17, p. 2259 - 2262]

44
[ 2160-38-5 ]
[ 643-28-7 ]
[ 1542913-20-1 ]

Yield	Reaction Conditions	Operation in experiment
84%	With 5,11,17,23,29,35,41,47-octakis(tert-butyl)-49,50,51,52,53,54,55,56-octakis(hydroxy)calix[8]arene In water at 25℃; for 2 - 2.5h;	General procedure for the synthesis of N-substituted 3,5-dinitrothiophene-2-amine compounds6aa-6av & 6ba-6bf (Scheme 2) General procedure: p-tert-Butylcalix[8]arene (129.6 mg, 0.1 mmol) was stirred in water(5 ml) in a 10 ml round bottomed flask for 30 minutes. Aryl or alkylamine (1 mmol) and 2-bromo-3,5-dinitrothiophene (1 mmol) were added to it and stirred for 2-2.5 h at 25 C. Greenish yellow colourcrude product-catalyst mixture was separated by simple filtration. Then the residue was dispersed in 10ml cold ethylacetate and stired for 5 minutes. The product was then dissolved in ethyl acetate and thecatalyst 1 seperated out as residue by filtration. The residue was further washed with cold ethyl acetate(2 ml) for three times and reuse for letter. All the EtOAc solution was taken in a 100 ml round bottomflaskand evaporated. Finally crystallization from ethyl acetate gave pure product in good to excellentyield (80-88%).
84%	With 5,11,17,23,29,35,41,47-octakis(tert-butyl)-49,50,51,52,53,54,55,56-octakis(hydroxy)calix[8]arene In water at 25℃;	General procedure for the synthesis of N-substituted 3,5-dinitrothiophene-2-amine compounds6aa-6av & 6ba-6bf General procedure: p-tert-Butylcalix[8]arene (129.6 mg, 0.1 mmol) was stirred in water(5 ml) in a 10 ml round bottomed flask for 30 minutes. Aryl or alkylamine (1 mmol) and 2-bromo-3,5-dinitrothiophene (1 mmol) were added to it and stirred for 2-2.5 h at 25 C. Greenish yellow colourcrude product-catalyst mixture was separated by simple filtration. Then the residue was dispersed in 10ml cold ethylacetate and stired for 5 minutes. The product was then dissolved in ethyl acetate and thecatalyst 1 seperated out as residue by filtration. The residue was further washed with cold ethyl acetate(2 ml) for three times and reuse for letter. All the EtOAc solution was taken in a 100 ml round bottomflaskand evaporated. Finally crystallization from ethyl acetate gave pure product in good to excellentyield (80-88%).

Reference： [1]Sarkar, Piyali; Maiti, Samares; Ghosh, Krishnendu; Sengupta, Sumita; Butcher, Ray J.; Mukhopadhyay, Chhanda [Tetrahedron Letters, 2014, vol. 55, # 5, p. 996 - 1001]
[2]Sarkar, Piyali; Maiti, Samares; Ghosh, Krishnendu; Bandyopadhyay, Sumita Sengupta; Butcher, Ray J.; Mukhopadhyay, Chhanda [Tetrahedron Letters, 2014, vol. 55, # 5, p. 996 - 1001]

45
[ 766-84-7 ]
[ 643-28-7 ]
[ 1584139-81-0 ]

Yield	Reaction Conditions	Operation in experiment
49.1%	Stage #1: 2-isopropylaniline With boron trichloride In dichloromethane; 1,2-dichloro-ethane at 0℃; for 0.166667h; Stage #2: 3-chloro-benzonitrile With aluminum (III) chloride In dichloromethane; 1,2-dichloro-ethane at 0 - 75℃; Stage #3: With hydrogenchloride; water In dichloromethane; 1,2-dichloro-ethane at 75℃;	Intermediate A-10: (2-Amino-3-isopropylphenyl)(3-chlorophenyl)methanone Intermediate A-10: (2-Amino-3-isopropylphenyl)(3-chlorophenyl)methanone 2-Isopropylaniline (3 mL, 21.19 mmol) was added dropwise to a solution of trichloroborane (1M in dichloromethane) (23.31 mL, 23.31 mmol) and dichloroethane (50 mL) at 0° C. and the mixture was stirred for 10 min. Next, 3-chlorobenzonitrile (5.83 g, 42.4 mmol), followed by aluminum trichloride (3.11 g, 23.31 mmol) were added and the mixture was stirred at 0° C. for 25 minutes. The ice bath was removed and the mixture was heated to 75° C. overnight. The mixture was then cooled to room temperature. Next, 6N HCl (60 mL, 10 eq) was added and the mixture was heated to 75° C. After 4 hrs, 12N HCl (10 mL) was added and heating was continued overnight at 75° C. The mixture was cooled to room temperature, transferred to an Erlenmeyer flask, diluted with ethyl acetate, cooled to 0° C., and cautiously raised to pH 10 with 50% aqueous NaOH. The resulting mixture was extracted with ethyl acetate (4). The ethyl acetate extracts were combined, washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated to give a clear amber oil. The oil was suspended in a minimum of heptane and purified on an ISCO companion chromatography system (220 g silica cartridge, eluting with 0-20% ethyl acetate/heptane, 150 mL/min) to provide Intermediate A-10 (2.85 g, 10.41 mmol, 49.1% yield). HPLC RT=3.876 min 10/90 to 90/10 (MeOH/H2O/0.1% TFA, Waters Sunfire C18 3.5 μm, 2.130 mm, 1 mL/min, 4 min gradient, wavelength=254 nm); MS (ES): m/z=274 [M+H+]; 1H NMR (400 MHz, chloroform-d) δ 7.63 (t, J=1.7 Hz, 1H), 7.55-7.48 (m, 2H), 7.44-7.29 (m, 3H), 6.65 (t, J=7.7 Hz, 1H), 6.43 (br. s., 2H), 3.11-2.87 (m, 1H), 1.34 (d, J=6.8 Hz, 6H).
49.1%	Stage #1: 2-isopropylaniline With boron trichloride In dichloromethane; 1,2-dichloro-ethane at 0℃; for 0.166667h; Stage #2: 3-chloro-benzonitrile With aluminum (III) chloride In dichloromethane; 1,2-dichloro-ethane at 0 - 75℃; Stage #3: With hydrogenchloride In dichloromethane; 1,2-dichloro-ethane at 20 - 75℃;	Intermediate A-ll: (2-Amino-3-isopropylphenyl)(3-chlorophenyl)methanone [00204] 2-Isopropylaniline (3 mL, 21.19 mmol) was added dropwise to a 0 oc solutionoftrichloroborane (1M in dichloromethane) (23.31 mL, 23.31 mmol) and dichloroethane(50 mL) and the mixture was stirred for 10 min. 3-Chlorobenzonitrile (5.83 g, 42.4mmol), followed by aluminum trichloride (3 .11 g, 23.31 mmol) were added and the5 mixture was stirred at 0 oc for a 25 minutes. The ice bath was removed and the mixturewas heated to 75 oc overnight. The mixture was cooled to room temperature. 6N HCl(60 mL, 10 eq) was cautiously added and the mixture was heated to 75 °C. After 4 hrs,12 N HCl (10 mL) was added and heating was continued overnight at 75 °C. The mixturewas cooled to room temperature, transferred to an Erlenmeyer flask, diluted with ethyl10 acetate, cooled to 0 oc and cautiously brought to pH 10 with 50% aqueous NaOH. Theresulting mixture was extracted with ethyl acetate (4x). The ethyl acetate extracts werecombined, washed with brine, dried over anhydrous sodium sulfate, filtered andconcentrated to give a clear amber oil. The oil was suspended in a minimum of heptaneand purified on an ISCO companion chromatography system (220 g silica cartridge,15 eluting with 0-20% ethyl acetate/heptane, 150 mL/min) to provide Intermediate A-ll(2.85 g, 10.41 mmol, 49.1% yield). HPLC RT= 3.876 min 10/90 to 90/10(MeOH/H20/0.1 %TFA, Waters SunFire C18 3.5-l, 2.1x30mm, lmL/min, 4 min gradient,wavelength=254 nm); MS(ES): m/z=274 [M+ 1]; 1H NMR (400MHz, chloroform-d) 87.63 (t, 1=1.7 Hz, IH), 7.55-7.48 (m, 2H), 7.44-7.29 (m, 3H), 6.65 (t, 1=7.7 Hz, IH), 6.4320 (br. s., 2H), 3.11-2.87 (m, IH), 1.34 (d, 1=6.8 Hz, 6H).

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US2014/87992, 2014, A1 Location in patent: Paragraph 0308-0309
[2]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2014/47397, 2014, A1 Location in patent: Paragraph 00204

46
[ 1444336-77-9 ]
[ 643-28-7 ]
[ 1444335-78-7 ]

Yield	Reaction Conditions	Operation in experiment
99%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene for 2h; Reflux;	4.2.18. 5-Benzyloxy-N-(2-isopropylphenyl)-3,4,6-trimethylpyridin-2-amine (14g) 2-Isopropylaniline (1.03mL, 7.35mmol) was added to a mixture of13(1.5g, 4.90mmol), NaOtBu (680mg, 6.86mmol), Pd2(dba)3(101mg, 0.10mmol), BINAP (125mg, 0.20mmol) in toluene (25mL) and the resulting mixture was refluxed for 2h. The mixture was cooled to room temperature, and then diluted with EtOAc (500mL) and water. The organic layer was washed with brine (20mL×5). The organic solution was dried over MgSO4and concentrated. The residue was purified by silica gel column chromatography (CHCl3:MeOH=99:1) to give14g(1.78g, 99%) as a brown solid. m.p. 70°C;1H NMR (CHCl3-d)δ7.25-7.49 (m, 7H), 7.06-7.13 (m, 1H), 6.94-7.01 (m, 1H), 5.92 (s, 1H), 4.77 (s, 2H), 3.13-3.24 (m, 1H), 2.42 (s, 3H), 2.23 (s, 3H), 2.03 (s, 3H), 1.32 (s, 3H), 1.29 (s, 3H) ppm;13C NMR (CHCl3-d)δ149.9, 147.1, 147.0, 140.0, 139.9, 137.6, 137.5, 128.7, 128.3, 128.1, 126.2, 125.6, 122.1, 119.6, 118.3, 75.2, 27.9, 22.9, 19.3, 14.1, 13.2ppm; IR (KBr) ν 3483, 3031, 2963, 1749, 1716, 1698, 1683, 1602, 1521, 1472, 1455, 1418, 1395, 1363, 1294, 1218, 1091, 1019, 750, 730, 693, 444, 418cm-1; MS (ES-API) [M+H]+361.
99%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene at 120℃; for 2h; Reflux;	22 <Example 22> Synthesis of 5-(benzyloxy)-N-(2-isopropylphenyl)-3,4,6-trimethylpyridin-2-amine; 5h 2-isopropylaniline (1.03 mL, 7.35 mmol) was added to a toluene (25 mL) solution of Compound 4 (1.5 g, 4.90 mmol), NaOtBu (680 mg, 6.86 mmol), Pd=DBA)3 (101 mg, 0.10 mmol), and BINAP (125 mg, 0.20 mmol), and then, the mixture was refluxed while stirring at a temperature of 120□ for 2 hours. The reaction solution was cooled to room temperature and then diluted with EtOAc (500 mL) and water (10 mL), and the EtOAc solution was washed with saturated saline water (20 mLX5). The result was dried with MgSO4, filtered, and concentrated under reduced pressure. The residual was purified by column chromatography (CHCl3:MeOH=99:1) to obtain Compound 5h (1.78 g, 99%) in the form of brown solid. 1H-NMR (250 MHz, CHCl3-d) δ 7.257.49 (m, 7H), 7.067.13 (m, 1H), 6.947.01 (m, 1 H), 5.92 (s, 1 H), 4.77 (s, 2H), 3.133.24 (m, 1 H), 2.42 (s, 3H), 2.23 (s, 3H), 2.03 (s, 3H), 1.32 (s, 3H), 1.29 (s, 3H) ppm.
	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate In toluene for 3h; Reflux;	Generalsynthetic procedure for compounds (6 or 7) General procedure: Primary amines(4, 1.10 mmol) or secondaryamines (5, mmol) was added to a mixture of 3 (1.0 mmol), NaOtBu (1.41 mmol), Pd2(dba)3 (0.05mmol), BINAP (0.10 mmol) in toluene (4 mL) and the resulting mixture wasrefluxed for 3 h. The mixture was cooled to room temperature, and then dilutedwith EtOAc (70 mL) and water. The organic layer was washed with brine (40 mL x3). The organic solution was dried over MgSO4 and concentrated. Theresidue was purified by silica gel column chromatography. Newcompounds (6: e-g, k-p,r-v, x-z, and ab; 7: a-e, g-h, and k) were synthesized under similar conditions.

Reference： [1]Kim, Dong-Guk; Kang, Youra; Lee, Hyunji; Lee, Eun Kyung; Nam, Tae-Gyu; Kim, Jung-Ae; Jeong, Byeong-Seon [European Journal of Medicinal Chemistry, 2014, vol. 78, p. 126 - 139]
[2]Current Patent Assignee: YEUNGNAM UNIVERSITY - EP2796450, 2014, A1 Location in patent: Paragraph 0080-0081
[3]Banskota, Suhrid; Kang, Han-eol; Kim, Dong-Guk; Park, Sang Won; Jang, Hyeonjin; Karmacharya, Ujjwala; Jeong, Byeong-Seon; Kim, Jung-Ae; Nam, Tae-gyu [Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 19, p. 4587 - 4591]

47
[ 50-00-0 ]
[ 939-19-5 ]
[ 643-28-7 ]
[ 1612849-47-4 ]

Yield	Reaction Conditions	Operation in experiment
79%	With titanium(IV) dioxide In ethanol; water at 25 - 28℃; for 6h;	General experimental procedure for the synthesis of chromeno-oxazine derivatives General procedure: A mixture of 3-hydroxycoumarin (1mmol), amine (1 mmol), formaldehyde (2.2mmol, 37-41 % aqueous solution) and a catalytic amount of TiO2 nanopowder (10 mol %) inethyl alcohol (5 mL) were taken in a 25 mL round-bottomed with stirring at rt (25-28°C) open to air for 4-6 hours. The progress of the reaction was monitored by TLC. After the completion of the reaction, the reaction mixture was filtered to remove TiO2 nanopowder.The solvent ethyl alcohol was then pumped out by rotary evaporation. The crude product thus obtained was purified directly by recrystallization from ethyl alcohol-water mixture (5:1 v/v).The spectral and analytical data of all compounds (4a-4q) reported in Table 2, are given below.

Reference： [1]Mondal, Animesh; Rana, Sunil; Mukhopadhyay, Chhanda [Tetrahedron Letters, 2014, vol. 55, # 24, p. 3498 - 3502]

48
[ 431-03-8 ]
[ 643-28-7 ]
[ 49673-33-8 ]

Yield	Reaction Conditions	Operation in experiment
90.5%	With formic acid In methanol for 12h; Reflux; Inert atmosphere;	Synthesis and characterization of the ligands and Co(II)complexes General procedure: For synthesis of ligand 2a, a reaction mixture of 2,3- butanedione(2.0 g, 0.023 mol), aniline (4.33 g, 0.047 mol), a few dropsof formic acid and methanol (20 ml) was refluxed for 12 h andcooled to room temperature. A yellow crystal-like solid precipitated after several hours.

Reference： [1]Jia, Xiangyu; Liu, Heng; Hu, Yanming; Dai, Quanquan; Bi, Jifu; Bai, Chenxi; Zhang, Xuequan [Cuihua Xuebao/Chinese Journal of Catalysis, 2013, vol. 34, # 8, p. 1560 - 1569]

49
C₂₂H₁₅NO [ No CAS ]
[ 643-28-7 ]
C₃₁H₂₆N₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: 2-isopropylaniline With 1,4-diaza-bicyclo[2.2.2]octane; titanium tetrachloride In toluene for 2h; Stage #2: C₂₂H₁₅NO In toluene at 140℃; for 36h;	Synthesis of ligand 4a General procedure: Aniline (7.22 mmol, 0.36 mL) and Dabco (21.6 mmol, 2.42 g) were stirred in toluene (55 mL) and 4.0 M solution of TiCl4 (7.2 mmol, 1.8 mL) in toluene was added. After 2 h, 3 (4.8 mmol, 1.48 g) was added and the reaction was refluxed at 140 °C for 36 h. The precipitate was removed by filtration. The filtrate was evaporated and dried in vacuo. Finally, deep red crystalline solid was isolated by silica gel column chromatography (hexane/ethyl acetate, 8:1) and recrystallized in hexane.

Reference： [1]Sa, Seokpil; Jeon, Manseong; Kim, Sang Youl [Journal of Molecular Catalysis A: Chemical, 2014, vol. 393, p. 263 - 271]

50
[ 39998-81-7 ]
[ 643-28-7 ]
3-fluoro-N-(2-isopropylphenyl)-4-methylaniline [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2015,vol. 2015,p. 6515 - 6525

51
[ 21375-88-2 ]
[ 643-28-7 ]
2-isopropyl-N-(2-(phenylethynyl)phenyl)aniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With palladium diacetate; tris-(o-tolyl)phosphine; sodium t-butanolate In toluene at 100℃; for 13h;	4.2.1 2-tert-Butyl-N-(2-(cyclohexylethynyl)phenyl)aniline (1c) General procedure: To a solution of (Ph3P)2PdCl2 (42mg, 0.06mmol) and CuI (24mg, 0.1mmol) in Et3N (4mL) were added 2-bromo-iodobenzene (0.38mL, 3.0mmol) and ethynylcyclohexane (0.39mL, 3.0mmol) at rt. After being stirred for 23h at rt, the mixture was poured into saturated NH4Cl aq and extracted with AcOEt. The AcOEt extracts were washed with brine, dried over MgSO4, and evaporated to dryness. Purification of the residue by column chromatography (hexane only) gave 1-bromo-2-(cyclohexylethynyl)benzene (777mg, 98%). To a solution of Pd(OAc)2 (27mg, 0.12mmol) and (o-tol)3P (71mg, 0.23mmol), t-BuONa (421mg, 4.4mmol) in toluene (10mL) were added 1-bromo-2-(cyclohexylethynyl)benzene (769mg, 2.9mmol) and 2-tert-butylaniline (0.46mL, 2.9mmol) at rt. After being stirred for 13h at 100°C, the mixture was poured into saturated NaHCO3 aq and extracted with AcOEt. The AcOEt extracts were washed with brine, dried over Na2SO4, and evaporated to dryness. Purification of the residue by column chromatography (hexane only) gave 1c (534mg, 55%).

Reference： [1]Morimoto, Yudai; Shimizu, Satoshi; Mokuya, Ayano; Ototake, Nobutaka; Saito, Akio; Kitagawa, Osamu [Tetrahedron, 2016, vol. 72, # 34, p. 5221 - 5229]

52
[ 20781-86-6 ]
[ 643-28-7 ]
N-2,6-diisopropylphenyl-2-(2-isopropylphenylamino)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With potassium carbonate; potassium iodide; potassium bromide In N,N-dimethyl-formamide at 80℃; for 16h; Inert atmosphere;	5 Under an argon atmosphere, into a reaction vessel of 2-chloro-N- (2,6-diisopropylphenyl) acetamide 5.08 g (20.0 mmol), potassium iodide 3.45 g (20.8 mmol), potassium bromide 1.07 g ( 8.99mmol), potassium carbonate 3.54g (25.6mmol), N, N- dimethylformamide 10mL and 2-isopropyl-aniline 4.05g a (30.0mmol) were added.The reaction vessel was heated to 80 , and the mixture was stirred for 16 hours.The reaction vessel was cooled to room temperature, ethyl acetate 200mL was added, the organic layer was washed with water 100 mL, saturated brine 100 mL, dried over sodium sulfate.Distilling off the sodium sulfate and the solvent, the residue was purified by silica gel column chromatography (hexane: ethyl acetate = 10: 0-9: 1) to give, N-2,6-diisopropyl-phenyl-2- (2-isopropyl was obtained phenylamino) acetamide 4.42 g (white solid, 12.5mmol, 63% yield)

Reference： [1]Current Patent Assignee: SAGAMI CHEMICAL RESEARCH INSTITUTE - JP2015/168640, 2015, A Location in patent: Paragraph 0117 - 0119

53
[ 21512-16-3 ]
[ 643-28-7 ]
5-((2-isopropylanilino)methyl)thiophene-2-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium cyanoborohydride; In methanol; at 20℃;	<strong>[21512-16-3]5-formylthiophene-2-carbonitrile</strong> (1 mmol) and 2-isopropylaniline (1 mmol) were dissolved in methanol (10 mL) and sodium cyanoborohydride (188 mg).One drop of concentrated hydrochloric acid was allowed to react at room temperature overnight, and the crude solution was spun dry and used directly in the next step.

Reference： [1]ChemMedChem,2017,vol. 12,p. 319 - 326
[2]Patent: CN103980264,2016,B .Location in patent: Paragraph 0147; 0148; 0149

54
[ 78078-92-9 ]
[ 643-28-7 ]
N-(2-isopropylphenyl)-2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamide [ No CAS ]

Reference： [1]Journal of Chemical Information and Modeling,2017,vol. 57,p. 355 - 364

55
[ 4481-56-5 ]
[ 643-28-7 ]
C₂₆H₂₅NO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With C₄₄H₄₅O₄P In fluorobenzene at 50℃; for 20h; Inert atmosphere; enantioselective reaction;	General Procedure for Aza-Piancatelli Rearrangement General procedure: To a flame-dried screw-capped vial equipped with magnetic stir bar, 2-furylcarbinolderivative (0.1 mmol, 1 equiv.) and aniline derivative (0.12 mmol, 1.2 equiv.) were added. Thenfluorobenzene (4 mL) was added at room temperature and stirred for 10 min. To this mixtureBrnsted acid (4g) (0.005 mmol, 5 mol%) was added under a stream of N2 flow. Reaction vialwas fitted with a cap and allowed to stir at 50° C for 20 h. After complete conversion of starting material as monitored by TLC, reaction mixture was filtered through plug of celite. The filtrate was concentrated and the residue thus obtained was purified by silica gel column chromatography using Pet. ether/EtOAc as an eluent to afford analytically pure compounds

Reference： [1]Gade, Amol B.; Patil, Nitin T. [Synlett, 2017, vol. 28, # 9, p. 1096 - 1100]

56
[ 423-39-2 ]
[ 7188-38-7 ]
[ 643-28-7 ]
N-(tert-butyl)-2,2,3,3,4,4,5,5,5-nonafluoro-N'-(2-isopropylphenyl)pentanimidamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With triethylamine In 1,4-dioxane at 110℃; Inert atmosphere; Green chemistry;	General experimental procedure General procedure: An oven-dried tube was evacuated and backfilled with N2 (5x). 1,4-dioxane (2.5 mL),amine (0.5 mmol), perfluoroalkyl iodide (1.0 mmol), and tert-butyl isocyanide (0.5mmol) were added into the tube. The reaction mixture was stirred at 110 °C for 24-28h. After the reaction was complete, the mixture was filtrated and concentrated under vacuum. The crude product was purified by flash column chromatography on silica gel(petroleum ether) to afford the product.

Reference： [1]Ai, Han-Jun; Cai, Chuang-Xu; Qi, Xinxin; Peng, Jin-Bao; Ying, Jun; Zheng, Feng; Wu, Xiao-Feng [Tetrahedron Letters, 2017, vol. 58, # 38, p. 3751 - 3753]

57
[ 643-28-7 ]
[ 205993-26-6 ]
2-(2,6-diisopropylphenyl)amino-4-(2-isopropylphenyl)imino-2-pentene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	Stage #1: 2-isopropylaniline With toluene-4-sulfonic acid In toluene at 20℃; for 3h; Inert atmosphere; Stage #2: 4-((2,6-di(isopropyl)phenyl)amino)-pent-3-en-2-one In toluene for 24h; Dean-Stark; Inert atmosphere; Reflux;
72.2%	Stage #1: 2-isopropylaniline With toluene-4-sulfonic acid In toluene at 20℃; for 3h; Stage #2: 4-((2,6-di(isopropyl)phenyl)amino)-pent-3-en-2-one In toluene at 20℃; for 24h; Reflux; Stage #3: With sodium hydrogencarbonate In diethyl ether; water for 3h;	8 Synthesis of Ligand L8 Add 2-isopropylaniline to a 250 mL three-necked flask(3.44g, 25.72mmol),P-toluenesulfonic acid·H2O (4.75 g, 25.0 mmol),70mL of toluene,Stir at room temperature for 3 h.Add to the above reaction solution4-(2,6-diisopropylphenyl)amino-3-penten-2-one (6.50, 25.0 mmol),Install the water separator,Heat to reflux for 24 h.Cool to room temperature,The solvent was removed under reduced pressure to give a dark red solid.Add 25mL of water,25 mL of diethyl ether and sodium bicarbonate (2.50 g, 25.0 mmol),Stir for 3h,Liquid separation,The aqueous phase was extracted twice with diethyl ether.Combine the organic phase,After the obtained organic phase is dried over anhydrous magnesium sulfate,The solvent was removed to give a yellow solid.Recrystallized from methanol6.6g pale yellow needle crystal L8,The yield was 72.2%.

Reference： [1]Keram, Maryam; Ma, Haiyan [Applied Organometallic Chemistry, 2017, vol. 31, # 12]
[2]Current Patent Assignee: EAST CHINA UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN103289071, 2016, B Location in patent: Paragraph 0069; 0070; 0071; 0072; 0073

58
[ 26487-67-2 ]
[ 643-28-7 ]
N-[2-(azepan-1-yl)ethyl]-2-isopropylaniline [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 98 - 118

59
[ 26487-67-2 ]
[ 643-28-7 ]
N-[2-(azepan-1-yl)ethyl]-2-isopropylaniline hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 98 - 118

60
[ 13235-60-4 ]
[ 643-28-7 ]
N1,N3-bis(2-isopropylphenyl)-4-methoxyisophthalamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70.83%	Stage #1: 4-methoxy-1,3-benzenedicarbonyl dichloride; 2-isopropylaniline In tetrahydrofuran; dichloromethane at 20℃; for 10h; Stage #2: With triethylamine In tetrahydrofuran; dichloromethane at 20℃; for 24h;	N1,N3-bis(2-ethylphenyl)-4-methoxyisophthalamide (1d) General procedure: A round-bottomed flask (100 ml) equipped with a magneticstirrers was charged with 2-ethylaniline (10.0 mmol, 1.2 g)in anhydrous tetrahydrofuran (15 ml). The fresh 4-methoxyisophthaloyl dichloride 5 (5.0 mmol, 1.2 g) in drytetrahydrofuran (15 ml) was added drop-wise to the abovesolution at room temperature. Ten hours after the additionof compound 5, dry triethylamine (1 ml) was added dropwiseto the reaction mixture. The resultant mixture reactionwas stirred for 24 h at room temperature. After the reactioncompleted as monitored by thin layer chromatography(TLC). The solvent was removed under reduced pressure toobtain the crude product. The crude product was furtherpurified by recrystallization from anhydrous ethanol to yieldthe desired product 1d as white solid. Yield: 55.00%

Reference： [1]Liu, Xiujie; Wang, Yan; Liu, Lili; Chen, Guangling [Medicinal Chemistry Research, 2018, vol. 27, # 8, p. 1971 - 1983]

61
[ 431-03-8 ]
[ 643-28-7 ]
C₁₃H₁₇NO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98.6%	In water at 20℃; for 72h;	3 Synthesis of ligand having formula (L3) The following were loaded into a 250 ml glass reactor, equipped with a magnetic stirrer, in this order: deionized water (70 ml), 2,3-butanedione (19.62 g; 227.9 mmoles) and, by dripping, 2-iso-propylaniline (13.56 g; 100.3 mmoles). The reaction mixture obtained was left, under stirring, at room temperature, for 72 hours, obtaining the formation of two layered phases, i.e. an organic phase and an aqueous phase. Subsequently, the organic phase was separated from the aqueous phase through a separator funnel, then it was washed, in succession, with deonized water (2 x 10 ml) and brine (15 ml), anhydrified on sodium sulfate (Na2SO4), filtered and finally purified by fractional distillation under vacuum using a Vigreux column, obtaining 20.1 g of a yellow oil (yield = 98.6%) corresponding to the ligand having formula (L3), which was stored, in an inert atmosphere, in the fridge.Elementary analysis [found (calculated) for C13H17N0]: C: 76.65% (76.81%); H: 8.25% (8.43%); N: 6.89% (6.89%).Molecular weight (MW): 203.28.GC-MS: M mlz 203.FT-IR (t.q.): 1702 cm1 v(c0); 1650 cm1 v(cN).1H-NMR [(C3D60) 6 ppm]: 1,15; 1,16 [both d, 3H each, CH(CH3)2]; 1,90; 2,46 (both s, 3H each, CH3); 2,97 [m, 1H, CH(CH3)2]; 6,61-7.34 (m, 4H, HAr).

Reference： [1]Current Patent Assignee: ENI SPA - WO2018/134757, 2018, A1 Location in patent: Page/Page column 35; 36

62
[ 643-28-7 ]
[ 19165-26-5 ]
3-(2-iso-propylphenyl)-2-ethylquinazolin-4(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With phosphorus trichloride In toluene at 20 - 130℃; for 7.5h; Inert atmosphere; diastereoselective reaction;	3-(2-Fluorophenyl)-2-ethylquinazolin-4(3H)-one (1a). Under N2 atmosphere, to2-fluoroaniline (278 mg, 2.5 mmol) and N-propionyl anthranilic acid (386 mg, 2.0 mmol) in toluene(6.0 mL) was added PCl3 (412 mg, 3.0 mmol), and the reaction mixture was stirred for 30 min at rtand for 7 h at 130 °C. The mixture was poured into water and extracted with AcOEt. The AcOEtextracts were washed with brine, dried over MgSO4, and evaporated to dryness. Purification of theresidue by column chromatography (hexane/AcOEt = 4) gave 1a (499 mg, 93%). 1a: white solid;mp 85-86 °C;

Reference： [1]Matsuoka, Mizuki; Iida, Asumi; Kitagawa, Osamu [Synlett, 2018, vol. 29, # 16, p. 2126 - 2130]

63
[ 91-01-0 ]
[ 643-28-7 ]
[ 1401109-96-3 ]

Yield	Reaction Conditions	Operation in experiment
84.5%	With hydrogenchloride; zinc(II) chloride In water at 120 - 160℃; for 0.5h;	Procedure for the Synthesis of Anilines General procedure: A 150 mL thick wall pressure bottle was charged with o-Toluidine (2.14 g, 20 mmol, 1.0 equiv.) and Benzhydrol (7.37 g, 40 mmol, 2.0 equiv.), and heated to 120 °C. A solution of anhydrous zinc chloride (0.68 g, 5 mmol, 0.5 equiv.) in concentrated hydrochloric acid (0.83 ml, 37% in H2O, 1.0 equiv.) was added to the mixture (exothermic + intense bubbling), and the temperature was raised to 160 °C. After 30 min at 160 °C, the reaction mixture was cooled to room temperature and dissolved in CH2Cl2 (200 mL). The CH2Cl2 layer was washed with water (3 × 100 mL) and dried over anhydrous magnesium sulfate. The solution was concentrated to 20 mL. The product was crashed out with 200 ml methanol and washed with methanol (3 × 100 mL). The desired aniline was obtained as a white crystalline solid at 75.2 % (6.61 g) yield. 1H NMR (500 MHz, CDCl3) δ 7.22 - 7.16 (m, 10H, Ar-H), 7.12 (dd, J = 8.4, 6.1 Hz, 2H, Ar-H), 7.03 (d, J = 7.1 Hz, 4H, Ar-H), 6.99 (d, J = 7.2 Hz, 4H, Ar-H), 6.75 (s, 1H, Ar-H), 6.29 (s, 1H, Ar-H), 5.43 (s, 1H, CHPh2), 5.27 (s, 1H, CHPh2), 3.37 (s, 2H, N-H), 2.08 (s, 3H, CH3). 13C NMR (126 MHz, CDCl3) δ 144.81, 142.62, 140.75, 133.01, 129.79, 129.50, 128.46, 128.13, 126.60, 125.95, 122.46, 56.24 (CHPh2), 52.53 (CHPh2), 17.94 (CH3). ESI-MS (m/z): calcd for C33H30N: 440.2378(m/s), found: 440.2362 [M+H]+.

Reference： [1]Guo, Lihua; Liu, Yanlan; Sun, Wenting; Du, Qing; Yang, Yuliang; Kong, Wenyu; Liu, Zhe; Chen, Darui [Journal of Organometallic Chemistry, 2018, vol. 877, p. 12 - 20]

64
7-chloro-9,9-diethyl-9H-fluorene-2-carbonitrile [ No CAS ]
[ 643-28-7 ]
7-(2-isopropylphenylamino)-9,9-diethyl-9H-fluorene-2-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With bis(dibenzylideneacetone)-palladium⁽⁰⁾; sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate In toluene at 79 - 81℃; for 4.5h; Inert atmosphere; Cooling;	33 7-(2-Isopropylphenylamino)-9,9-diethyl-9H-fluorene-2-carbonitrile (33) (2010-38) A mixture of 7-chloro-9,9-diethylfluorene-2-nitrile (11.13 g, 39.45 mmol), 2-isopropyl aniline (7.45 g, 55 mmol), and toluene (110 mL) was azeotroped dry under nitrogen and cooled. Bis(dibenzylideneacetone)palladium(0) (376.1 mg (0.654 mmol), tri-t-butylphosphonium tetrafluoroborate (166.8 mg), and sodium-t-butoxide (4.62 g, 48 mmol) were added, and the mixture was held at 79-81° C. for 4.5 hours. After cooling and dilution with toluene, the toluene solution was washed with water, dried and concentrated. The residue (18.49 g) was chromatographed over silica gel, and elution with 65% toluene-heptane gave the product, 14.6 g (97%), m.p. 111.3-113° C. (hexanes). Mass spec: m/z 380 (M+). Analysis: Calcd for C27H28N2: C, 85.22; H, 7.42 and N, 7.36%. Found: C, 85.27; H, 7.44 and N, 7.26%. 1H NMR (CDCl3) δ ppm: 0.33 (t, 6H, 7.30 Hz), 1.25 (d, 6H, 6.84 Hz), 1.94 (m, 4H), 3.2 (septet, 1H, 6.8 Hz), 5.68 (s, 1H), 6.78 (s, 1H), 6.84 (d, 1H, 8.12 Hz), 7.17 (m, 2H), 7.28 (d, 1H, 7.6 Hz), 7.35 (d, 1H, 7.4 Hz), 7.49 (s, 1H), 7.57 (m, 3H). 13C NMR δ ppm: 8.68, 23.42, 28.01, 32.87, 56.54 (5 sp3C), 108.06, 109.99, 115.52, 118.96, 120.56, 122.07, 123.33, 124.73, 126.34, 126.63, 128.88, 131.54, 131.73, 139.09, 142.13, 146.91, 147.33, 150.06, and 152.97 (19 sp2- and sp-C).

Reference： [1]Current Patent Assignee: GOVERNMENT OF THE UNITED STATES - US10113065, 2018, B1 Location in patent: Page/Page column 34

65
[ 225113-41-7 ]
[ 643-28-7 ]
[N,7-(benzothiazol-2-yl)-9,9-diethylfluoren-2-yl]-2-isopropylphenylamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With 1,1'-bis-(diphenylphosphino)ferrocene; bis(dibenzylideneacetone)-palladium⁽⁰⁾; sodium t-butanolate In toluene at 92℃; for 4h; Inert atmosphere; Cooling;	18 N,7-[(benzothiazol-2-yl)-9,9-diethylfluoren-2-yl]-2-isopropylphenylamine A mixture of 2-(7-bromo-9,9-diethylfluoren-2-yl)benzothiazole (Example 4 10.85 g, 25 mmol), 2-isopropyl aniline (4.16 g, 30.8 mmol) and toluene (100 mL) was azeotroped dry under nitrogen and cooled. Bis(dibenzylidene acetone)palladium(0) (295.5 mg, 0.514 mmol), 1,1-bis(diphenylphosphino)ferrocene (292.4 mg, 0.528 mmol) and sodium t-butoxide (3.48 g, 36.2 mmol) were then added, and the mixture was held at 92° C. for 4 hours. After cooling and dilution with toluene, the toluene solution was washed with water, dried, and concentrated. The residue (39 g) was chromatographed over silica gel, and the column was eluted with 65% toluene-heptane to get the product, 11.44 g (93%), m.p. 193-195° C. Mass spec: m/z 488 (M+). Anal. Calcd. for C33H32N2S: C, 81.10, H, 6.60, N, 5.72 and S, 6.56%. Found: C, 81.19; H, 6.61; N, 5.72 and S, 6.55%. 1H NMR (CDCl3): δ ppm: 0.38 (t, 6H, 7.32 Hz), 1.27 (d, 6H, 6.84 Hz), 1.98 (m, 2H), 2.12 (m, 2H), 3.20 (septet, 1H, 6.82 Hz), 5.60 (s, 1H), 6.86 (m, 2H), 7.11 (td, 1H, 1.28, 7.56 Hz), 7.18 (t, 1H, 1.6 and 7.4 Hz), 7.33 (m, 3H), 7.48 (t, 1H, 8.24 Hz), 7.59 (d, 1H, 8.12 Hz), 7.65 (d, 1H, 7.92 Hz), 7.89 (d, 1H, 7.84 Hz), 7.99 (d, 1H, 1.56, 7.88 Hz), 8.07 (m, 2H). 13C NMR δ ppm: 8.58, 23.08, 27.69, 32.82, 56.33 (5 sp3C), 110.68, 115.64, 118.73, 121.17, 121.33, 121.50, 121.97, 122.85, 123.72, 124.84, 126.21, 125.55, 127.26, 130.79, 132.76, 134.89, 139.41, 140.86, 145.12, 145.77, 150.04, 152.64, 154.28 and 169.06 (24 sp2C).

Reference： [1]Current Patent Assignee: GOVERNMENT OF THE UNITED STATES - US10113065, 2018, B1 Location in patent: Page/Page column 19-20

66
[ 958489-67-3 ]
[ 643-28-7 ]
N-(2-isopropylphenyl)-3-nitro-[1,1'-biphenyl]-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With potassium fluoride at 180℃; for 18h;	Preparation of N-(2-isopropylphenyl)-3-nitro-[1,1'-biphenyl]-2-amine: 2-Fluoro-3-nitro-1,1'-biphenyl (6 g, 27.6 mmol), 2-isopropylaniline (19.56 ml, 138 mmol) and potassium fluoride (3.21 g, 55.2 mmol) were heated to 180 After °C for 18 hours. The crude material was diluted with ethyl acetate, filtered thru a pad and washed with brine.The organic layer was dried over MgSO 4 and solvent was evaporated. The crude product was purified by vacuum distillation. N-(2-Isopropylphenyl)-3-nitro-[1,1'-biphenyl]-2-amine (8.04 g, 88% yield) was obtained and used without further purification In the next step.

Reference： [1]Current Patent Assignee: UNIVERSAL DISPLAY CORP - CN103980321, 2018, B Location in patent: Paragraph 0285-0287

67
[ 60100-09-6 ]
[ 643-28-7 ]
[ 90874-73-0 ]

Yield	Reaction Conditions	Operation in experiment
77%	at 150℃; for 24h; Sealed tube; Green chemistry;
77%	With air at 150℃; for 24h; Sealed tube;	4 Example 4 2-isopropylaniline (145 μL, 1.0 mmol), formamide (0.4 mL, 10.0 mmol), and a stirrer were placed in a reaction tube, and the reaction tube was sealed under air. The reaction tube was placed in a 150 ° C oil bath reaction pot, and the reaction was stirred for 24 hours, cooled to room temperature, diluted with 15 mL of water, and extracted with ethyl acetate three times, 15 mL each time. The combined extracts were dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure, and the crude product was subjected to column chromatography with ethyl acetate: petroleum ether = 1:3 (1% triethylamine) as eluent. Get pure. Yellow solid, melting point 65-67 ° C, yield 77%

Reference： [1]Yin, Jiawen; Zhang, Jingyu; Cai, Changqun; Deng, Guo-Jun; Gong, Hang [Organic Letters, 2019, vol. 21, # 2, p. 387 - 392]
[2]Current Patent Assignee: XIANGTAN UNIVERSITY - CN109456216, 2019, A Location in patent: Paragraph 0037; 0038

68
[ 122-51-0 ]
[ 762-04-9 ]
[ 643-28-7 ]
C₁₈H₃₃NO₆P₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With sulfonic acid functionalized hyper-cross-linked 2,2′-biphenol polymer at 50℃; for 1h; Sealed tube;	2.2. General procedure for the synthesis of N-BPs General procedure: Aniline (1, 1 mmol), triethyl orthoformate (2, 1 mmol), dialkylphosphite (3, 2 mmol), and 10 mg of HCBP-SO3H were added into a 10 mL reaction vial. The vial was then sealed and the contents werestirred for 1 h at 50 °C. Upon completion (as indicated by TLC), the reaction mixture was cooled to ambient temperature and dissolved in ethyl acetate (10 mL). The resulting mixture was centrifuged and the ethyl acetate layer was separated. The organic extract was washed with brine, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to obtain the corresponding N-BP.

Reference： [1]Reddy, Sirigireddy Sudharsan; Kalla, Reddi Mohan Naidu; Varyambath, Anuraj; Kim, Il [Catalysis Communications, 2019, vol. 126, p. 15 - 20]

69
5-methyl-4-methoxy-1,3-benzenedisulfonylchloride [ No CAS ]
[ 643-28-7 ]
N1,N3-bis(2-isopropylphenyl)-4-methoxy- 5-methyl-1,3-benzenedisulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42.7%	With triethylamine In tetrahydrofuran at 20℃; for 24h;	General procedure for synthesis of compound (IV) (Take N1,N3-bis(2-isopropylphenyl)-4-methoxy- 5-methyl-1,3-benzenedisulfonamide (1a) as an example) 0.65 g (4.80 mmol) ortho isopropyl aniline, placed in100 ml single mouthed bottle, amount of 10 ml dissolvedin tetrahydrofuran, stirred with the magnetic stirrer;another 0.60 g (2.00 mmol) intermediate (IIIa) dissolved in 20 ml tetrahydrofuran, the solution is added drop bydrop into the single mouthed bottle, immediately formedwhite turbidity (monitored by TLC, ethylacetate-petroleum ether, volume ratio = 1:1). The solutionwas concentrated in vacuo, and the pH value was adjustedto 3.0-4.0 by hydrochloric acid, the solid was collectedand dried, residues were recrystallized from ethanol togive compound 1a (solid red light). Yield: 42.7%; m.p.:149.3-150 °C.

Reference： [1]Xiu-jie, Liu; Zhi-hao, Zhang; Qing-song, Deng; Xin, Chen; Chao-qing, Wang [Medicinal Chemistry Research, 2019, vol. 28, # 11, p. 1864 - 1872]

70
[ 1122-62-9 ]
[ 643-28-7 ]
[ 270928-28-4 ]

Yield	Reaction Conditions	Operation in experiment
79%	With toluene-4-sulfonic acid In toluene for 2h; Reflux;	5 Synthesis of Ligand Having Formula (L3) In a 500 ml flask, 2-acetylpyridine (3.78 g; 31.1 mmoles) and p-toluenesulfonic acid monohydrate (0.15 g; 0.81 mmoles) were added to a solution of 2-iso-propylaniline (4.20 g; 31.1 mmoles) in toluene (20 ml): the mixture obtained was heated under reflux, for 2 hours. Subsequently, the solvent was removed through vacuum evaporation and the residue obtained was purified through vacuum distillation, obtaining 5.89 g of an orange oil (yield=79%) corresponding to the ligand having formula (L3). FT-IR (nujol) (cm-1): 1637 (vC═N). Molecular weight (MW): 238. Elementary analysis [found (calculated for C16H18N2)]: C: 80.17% (80.63%); H: 7.804% (7.61%); N: 11.91% (11.75%). FT-IR (solid state, UATR) (cm-1): 1637 (vC═N). 1H NMR (400 MHz, 20° C., CDCl3): =8.71 (d, 1H), 8.37 (d, 1H), 7.81 (t, 1H), 7.38 (m, 2H), 7.22 (t, 1H), 7.15 (t, 1H), 6.67 (d, 1H), 3.05 (sept, 1H), 2.39 (s, 3H), 1.23 (d, 6H).
79%	With toluene-4-sulfonic acid In toluene for 2h; Reflux;	2 Synthesis of Ligand Having Formula (L2) In a 250 ml flask, 2-acetylpiridine (3.78 g; 31.1 mmoles) and p-toluenesulfonic acid monohydrate (0.15 g; 0.81 mmoles) were added to a solution of 2-iso-propylaniline (4.20 g; 31.1 mmoles) in toluene (20 ml): the mixture obtained was heated under reflux, for 2 hours. Subsequently, the solvent was removed through vacuum evaporation and the residue obtained was purified through vacuum distillation, obtaining 5.89 g of an orange oil (yield=79%) corresponding to the ligand having formula (L2).Molecular weight (MW): 238.33.Elementary analysis [found (calculated for C16H18N2)]: C: 80.17% (80.63%); H: 7.80% (7.61%); N: 11.91% (11.75%).1H-NMR (CDCl3, δ ppm) 8.71 (d, 1H), 8.37 (d, 1H), 7.81 (t, 1H), 7.38 (m, 2H), 7.22 (t, 1H), 7.15 (t, 1H), 6.67 (d, 1H), 3.05 (sept, 1H), 2.39 (s, 3H), 1.23 (d, 6H).
79%	With toluene-4-sulfonic acid In toluene for 2h; Reflux;	3 Synthesis of the Ligand Having the Formula (L3) 2-Acetylpyridine (3.78 g; 31.1 mmol) and p-toluenesulfonic acid monohydrate (0.15 g; 0.81 mmol) were added to a solution of 2-iso-propylaniline (4.20 g; 31.1 mmol) in toluene (20 ml), in a 500 ml reaction flask: the mixture obtained was refluxed for 2 hours. The solvent was then removed by vacuum evaporation and the residue obtained was purified by distillation under vacuum, 5.89 g of an orange oil (yield=79%), corresponding to the ligand having the formula (L3), being obtained. (0168) FT-IR (Nujol): (cm-1): 1637 (vC=N). (0169) Molecular weight (MW): 238. (0170) Elemental analysis [found (calculated for C16H18N2)]: C: 80.17% (80.63%); H: 7.80% (7.61%); N: 11.91% (11.75%). (0171) FT-IR (solid state, UATR) (cm-1): 1637 (vC=N). (0172) 1H-NMR (CDCl3, δ ppm) 8.71 (d, 1H), 8.37 (d, 1H), 7.81 (t, 1H), 7.38 (m, 2H), 7.22 (t, 1H), 7.15 (t, 1H), 6.67 (d, 1H), 3.05 (sept, 1H), 2.39 (s, 3H), 1.23 (d, 6H).

Reference： [1]Current Patent Assignee: ENI SPA - US2019/270832, 2019, A1 Location in patent: Paragraph 0193-0199
[2]Current Patent Assignee: ENI SPA - US2020/369805, 2020, A1 Location in patent: Paragraph 0116-120
[3]Current Patent Assignee: ENI SPA - US10954326, 2021, B2 Location in patent: Page/Page column 15-16

71
[ 643-28-7 ]
sodium (2-isopropylphenyl)sulfamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: 2-isopropylaniline With chlorosulfonic acid In dichloromethane at 0 - 20℃; for 2h; Stage #2: With sodium carbonate In water at 20℃;	1.2-1.1 Step 1: Sodium (2-isopropylphenyl)sulfamate. A solution of chlorosulfonic acid (2.0 mL, 30 mmol) in DCM (15 mL) was added dropwise over 30 min to a solution of 2-(methylethyl)phenylamine (13 mL, 90 mmol) in DCM (100 mL) at 0° C. After the addition was complete, the reaction mixture was allowed to warm to rt and was stirred for an additional 2 h. The reaction mixture was concentrated in vacuo. The residue was dissolved in an aqueous solution of sodium carbonate (100 rnL, 0.45 M). The resulting mixture was extracted twice with DCM. The aqueous phase was concentrated in vacuo. The residue was suspended in refluxing ethanol (60 mL) and the hot suspension was filtered. The filtrate was concentrated under reduced pressure to give sodium (2-isopropylphenyl)sulfamate as a white solid (6.2 g, 26 mmol, 87% yield). 1H NMR (DMSO-d6, 400 MHz):δ 7.46 (dd, J=8.2, 1.1 Hz, 1H), 7.07 (dd, J=7.7, 1.2 Hz, 1H), 6.98 (t, J=7.3 Hz, 1H), 6.77 (t, J=7.5 Hz, 1H), 6.34 (s, 1H), 3.06 (spt, J=6.8 Hz, 1H), 1.12 (d, J=6.8 Hz, 6H)Alternative work up for Step 1: After the reaction was complete, the reaction was filtered and the resulting solid was washed with DCM to afford the corresponding sulfamic acid. Both the sodium sulfamate and the sulfamic acid can be used in the next step.

Reference： [1]Current Patent Assignee: AMGEN INC - US2019/345169, 2019, A1 Location in patent: Paragraph 0208-0210

72
[ 79-37-8 ]
[ 643-28-7 ]
[ 142266-62-4 ]
2,5,6-trichloro-N-((2-isopropylphenyl)carbamoyl)nicotinamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74.4%		A suspension mixture of <strong>[142266-62-4]2,5,6-trichloronicotinamide</strong> (Intermediate P, 6.7 g, 29.7 mmol) in 1,2-dichloroethane (100 mL) was treated with oxalyl chloride (3.0 mL, 35.7 mmol) at rt. The resulting reaction mixture was stirred at 80 C. for 30 min then the white suspension was evaporated to give a slurry. The slurry was treated with acetonitrile (100 mL) and then with 2-isopropylaniline (4.6 mL, 32.7 mmol, Sigma-Aldrich Corporation, St. Louis, Mo., USA) at rt. The mixture was stirred for 15 min and the white solid was collected by filtration, washed with acetonitrile and dried to give pure 2,5,6-trichloro-N-((2-isopropylphenyl)carbamoyl)nicotinamide (8.55 g, 22.1 mmol, 74.4% yield) as a white solid. m/z (ESI, +ve ion): 386.0 (M+H)+.

Reference： [1]Journal of Medicinal Chemistry,2020
[2]Patent: US2019/374542,2019,A1 .Location in patent: Paragraph 0792-0793

73
[ 2524-52-9 ]
[ 643-28-7 ]
N-(2-isopropylphenyl)picolinamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With iron(III) chloride In neat (no solvent) at 80℃; Sealed tube;	Typical Experimental Procedure for FeCl3-Catalyzed Direct Amidation of Esters. General procedure: An oven-dried pressuretube equipped with a magnetic stirrer was evacuated with nitrogen. To this was added of ester 1a(492 uL, 5.04 mmol), followed by amine 2a (0.5 mL, 4.58 mmol), and finally FeCl3 (111 mg, 0.684 mmol).The mixture was then sealed and stirred at 80 C (0.5 mL of CH3CN was added if the reaction mixturesolidified). The reaction was monitored by TLC until completion upon which it was diluted withEtOAc and washed once with saturated NaHCO3 and once with distilled H2O. The combined aqueouslayers were extracted once with ethyl acetate. The combined organic layers were then dried overMgSO4, filtered and solvents removed under reduced pressure. The crude product was purified bysilica gel ash column chromatography using a combination of hexane and ethyl acetate (3:2).

Reference： [1]Mkhonazi, Blessing D.; Shandu, Malibongwe; Tshinavhe, Ronewa; Simelane, Sandile B.; Moshapo, Paseka T. [Molecules, 2020, vol. 25, # 5]

74
[ 16502-01-5 ]
[ 32315-10-9 ]
[ 643-28-7 ]
N-(2-isopropylphenyl)-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	Stage #1: bis(trichloromethyl) carbonate; 2-isopropylaniline With dmap In dichloromethane for 0.5h; Inert atmosphere; Stage #2: tetrahydrobetacarboline In dichloromethane at 20℃; for 12h; Inert atmosphere;	General procedure for the preparation of7. The solution oftriphosgene (0.88 mmol) in CH2Cl2(5 mL) was added dropwise to a stirred solution of aromatic amine (2.75 mmol) in CH2Cl2(20 mL) under nitrogen. Then DMAP (7.5 mmol) was added to the mixture. The reaction mixture was stirred for 30 min, followed by added solution of1,2,3,4-Tetrahydro-9H-pyrido[3,4-b]indole (5, 2.5 mmol)in CH2Cl2(20 mL) and stirred for an additional 12 h at room temperature. Upon completion of the reaction, 10 mL of water added to terminate the reaction. Then the organic layer was washed with 2N hydrochloric acid (40 mL × 2), saturated NaHCO3aqueous solution (40 mL × 2), aqueous brine (40 mL × 2), dried over Na2SO4, and concentrated to yield crude product. The residue was purified by flash column chromatography eluting with CH2Cl2/CH3OH (80:1) to obtain7a-w.

Reference： [1]Gao, Mengkang; Hu, Jing; Li, Qifei; Nie, Cunbin; Qian, Hai; Qiao, Yue; Qiao, Zhenrui; Wang, Qiang; Wang, Yusui; Yan, Lin [European Journal of Medicinal Chemistry, 2020, vol. 194]

75
[ 626-96-0 ]
[ 643-28-7 ]
1-(2-isopropylphenyl)-2-methyl-1H-pyrrole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With diphenyl hydrogen phosphate In dichloromethane at 20℃; for 2h;

Reference： [1]Chen, Shuming; Han, Feng; Houk, K. N.; Ivlev, Sergei; Meggers, Eric; Xie, Xiulan; Ye, Chen-Xi [Angewandte Chemie - International Edition, 2020, vol. 59, # 32, p. 13552 - 13556][Angew. Chem., 2020, vol. 132, # 32, p. 13654 - 13658,5]

76
[ 479067-56-6 ]
[ 32315-10-9 ]
[ 643-28-7 ]
(S)-N-(2-isopropylphenyl)-2-(4-phenylthiazol-2-yl)pyrrolidine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56.2%	Stage #1: bis(trichloromethyl) carbonate; 2-isopropylaniline With dmap In dichloromethane for 0.5h; Inert atmosphere; Stage #2: (S)-4-phenyl-2-(pyrrolidin-2-yl)thiazole In dichloromethane for 12h; Inert atmosphere;	4.2.5 General procedure for the preparation of 3, 4, 5 and 6 General procedure: The solution of substituted aniline (3.138mmol) in dry CH2Cl2 (20mL) was added dropwise to a stirred solution of triphosgene (317mg, 1.070mmol) in CH2Cl2 (20mL) under nitrogen. Then 4-dimethylaminopyridine (1.153g, 9.414mmol) was added to the mixture. The reaction mixture was stirred for 30min, followed by the addition of a solution of intermediate 11 in CH2Cl2 (20mL) and reacted overnight (12h). Water (2mL) was added to stop the reaction, the reaction solution was washed with brine (30mL×3), and the aqueous phase was extracted with CH2Cl2 (30mL×2). The combined organic layer was dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (CH2Cl2: MeOH=50:1) to obtain the target compound.
56.2%	Stage #1: bis(trichloromethyl) carbonate; 2-isopropylaniline With dmap In dichloromethane for 0.5h; Inert atmosphere; Stage #2: (S)-4-phenyl-2-(pyrrolidin-2-yl)thiazole In dichloromethane for 12h; Inert atmosphere;	4.2.5 General procedure for the preparation of 3, 4, 5 and 6 General procedure: The solution of substituted aniline (3.138mmol) in dry CH2Cl2 (20mL) was added dropwise to a stirred solution of triphosgene (317mg, 1.070mmol) in CH2Cl2 (20mL) under nitrogen. Then 4-dimethylaminopyridine (1.153g, 9.414mmol) was added to the mixture. The reaction mixture was stirred for 30min, followed by the addition of a solution of intermediate 11 in CH2Cl2 (20mL) and reacted overnight (12h). Water (2mL) was added to stop the reaction, the reaction solution was washed with brine (30mL×3), and the aqueous phase was extracted with CH2Cl2 (30mL×2). The combined organic layer was dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (CH2Cl2: MeOH=50:1) to obtain the target compound.
54.2%	Stage #1: bis(trichloromethyl) carbonate; 2-isopropylaniline With dmap In dichloromethane at 20℃; for 0.5h; Inert atmosphere; Stage #2: (S)-4-phenyl-2-(pyrrolidin-2-yl)thiazole In dichloromethane for 12h;	12.e (e) Preparation of (S)-N-(2-isopropylphenyl)-2-(4-phenylthiazol-2-yl)pyrrolidine-1-carboxamide (12) Under the protection of nitrogen at room temperature, add 2-isopropylaniline (0.42g, 3.138mmol) to a two-necked flask, stir to dissolve with 20mL of dry dichloromethane, and use 2mL of dichloromethane with triphosgene (0.28g, 0.941mmol) After dissolving, add dropwise slowly, then add 4-dimethylaminopyridine (1.01g, 8.28mmol), after reaction for 30min, add (S)-4-phenyl-2-(pyrrolidin-2-yl)thiazole (0.63g) , 2.76mmol) was dissolved in 10mL of dichloromethane and slowly added dropwise, and then reacted overnight (12h).Add 2mL of water to stop the reaction, wash the reaction solution with saturated brine (30mL×3), back-extract the aqueous phase with dichloromethane (30mL×2), combine the organic phases, evaporate the solvent under reduced pressure, and separate and purify by column chromatography (2 Methyl chloride: methanol = 100:1, volume ratio) to obtain a light yellow solid, (S)-N-(2-isopropylphenyl)-2-(4-phenylthiazol-2-yl)pyrrolidine-1 -Carboxamide, the yield is 54.2%.

Reference： [1]Chen, Yingda; Guo, Ning; He, Wenya; Qian, Hai; Qiao, Yue; Qiao, Zhenrui; Shao, Lulian; Song, Depu; Tian, Zhiyong; Wang, Guohao; Wang, Qiang; Yan, Lin; Zhang, Yang [European Journal of Medicinal Chemistry, 2022, vol. 233]
[2]Chen, Yingda; Guo, Ning; He, Wenya; Qian, Hai; Qiao, Yue; Qiao, Zhenrui; Shao, Lulian; Song, Depu; Tian, Zhiyong; Wang, Guohao; Wang, Qiang; Yan, Lin; Zhang, Yang [European Journal of Medicinal Chemistry, 2022, vol. 233]
[3]Current Patent Assignee: HENAN UNIVERSITY - CN111423432, 2020, A Location in patent: Paragraph 0050; 0124; 0134-0136

77
[ 16130-58-8 ]
[ 643-28-7 ]
[ 87165-41-1 ]

Yield	Reaction Conditions	Operation in experiment
88%	With triethylamine In dichloromethane at 20℃; for 3h;	1.2 Step 2: Synthesis of compound 1D The compound 1D-2 (11g) obtained in the previous step was dissolved in DCM (100mL), and then 2-isopropylaniline ID-3 (14.8g, 110mmol) and triethylamine (20.2g, 200mmol) were added, and then at room temperature Stir for 3 hours. After TLC showed that the reaction was complete, the solvent was removed under reduced pressure, and the resulting residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate = 10:1 (V:V volume ratio)) to obtain compound 1D (17.8 g, white solid) ), yield: 88%.

Reference： [1]Current Patent Assignee: BRIGHTGENE BIO MEDICAL TECHNOLOGY CO LTD - CN111484477, 2020, A Location in patent: Paragraph 0096; 0099; 0104-0106

78
[ 643-28-7 ]
[ 80194-69-0 ]
C₁₆H₁₅F₃N₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;

Reference： [1]Yao, Qi-Jun; Xie, Pei-Pei; Wu, Yong-Jie; Feng, Ya-Lan; Teng, Ming-Ya; Hong, Xin; Shi, Bing-Feng [Journal of the American Chemical Society, 2020, vol. 142, # 42, p. 18266 - 18276]

79
[ 885588-12-5 ]
[ 643-28-7 ]
2-bromo-5-((2-isopropylphenyl)amino)isonicotinic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	Stage #1: 2-isopropylaniline With sodium hexamethyldisilazane In tetrahydrofuran at -78℃; for 2.5h; Inert atmosphere; Stage #2: 2-bromo-5-fluoropyridine-4-carboxylic acid In tetrahydrofuran at -78℃; for 1h; Inert atmosphere;	42.1 Step 1: Dissolve 2-isopropylaniline (4.79g, 35.5mmoL) in 150mL tetrahydrofuran, protect with nitrogen, cool to -78°C, slowly inject NaHMDS (35.5ml, 71mmol, THF solution), add dropwise in 30 minutes , stir for 2 hours at -78°C. Continue to dropwise add NaHMDS (16ml, 32mmol, THF solution) and 2-bromo-5-fluoroisonicotinic acid (6g, 27.27mmol, THF solution) successively, raise to room temperature and react for 1 hour. After the reaction is complete, cool to room temperature, add 5 mL saturated ammonium chloride and 1M HCl to neutrality, extract with dichloromethane, concentrate to obtain a solid product, and purify with methanol to obtain the target product 2-bromo-5-((2-isopropylphenyl)amino)isonicotinic acid (6.3 g, Y: 69%).

Reference： [1]Current Patent Assignee: GENFLEET THERAPEUTICS SHANGHAI; ZHEJIANG GENFLEET PHARMACEUTICAL - CN112047937, 2020, A Location in patent: Paragraph 0293-0295

80
C₉H₇F₂N₃O₂S [ No CAS ]
[ 643-28-7 ]
2-(3-(difluoromethyl)-1-methyl-1H-pyrazol-4-yl)-N-(2-isopropylphenyl)thiazole-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: C₉H₇F₂N₃O₂S With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.25h; Stage #2: 2-isopropylaniline In dichloromethane at 20℃;	4.1.12. General procedure for target compounds 11aa-11eh General procedure: The carboxylic acids 10a-10e (1 equiv.) were dissolved indichloromethane, N, N-diisopropylethylamine (DIPEA, 2 equiv.) andBenzotriazol-1-yl- oxytripyrrolidinophosphonium hexafluorophosphate(PyBOP, 1.1 equiv.) were added at 0 °C. After 15 min, the corresponding amine (1.2 equiv.) was added. And then,the reaction mixture was stirred overnight at room temperature.The completion of the reaction was monitored by TLC, the solutionwas sequentially washed with water and brine, and extracted withdichloromethane. The combined organic layers were dried overanhydrous Na2SO4, then filtered and concentrated under reducedpressure. The crude residues were purified by silica gel columnchromatography to afford title compounds 11aa-11eh (30-99%).

Reference： [1]Yu, Bin; Zhao, Bin; Hao, Zesheng; Chen, Lei; Cao, Lixin; Guo, Xiaofeng; Zhang, Nailou; Yang, Dongyan; Tang, Liangfu; Fan, Zhijin [European Journal of Medicinal Chemistry, 2021, vol. 214]

81
3-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)benzoic acid [ No CAS ]
[ 643-28-7 ]
N-(2-isopropylphenyl)-3-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	Stage #1: 3-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)benzoic acid With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.25h; Stage #2: 2-isopropylaniline In dichloromethane at 20℃;	4.1.12. General procedure for target compounds 11aa-11eh General procedure: The carboxylic acids 10a-10e (1 equiv.) were dissolved indichloromethane, N, N-diisopropylethylamine (DIPEA, 2 equiv.) andBenzotriazol-1-yl- oxytripyrrolidinophosphonium hexafluorophosphate(PyBOP, 1.1 equiv.) were added at 0 °C. After 15 min, the corresponding amine (1.2 equiv.) was added. And then,the reaction mixture was stirred overnight at room temperature.The completion of the reaction was monitored by TLC, the solutionwas sequentially washed with water and brine, and extracted withdichloromethane. The combined organic layers were dried overanhydrous Na2SO4, then filtered and concentrated under reducedpressure. The crude residues were purified by silica gel columnchromatography to afford title compounds 11aa-11eh (30-99%).

82
[ 643-28-7 ]
[ 2038-44-0 ]
N1’,N2’-dihydroxy-N1,N2-bis(2-isopropylphenyl)oxalamidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With triethylamine In ethanol at -10 - 20℃;	2.2.1. Nucleophilic reaction between dichloroglyoxime and substituted aryl amines General procedure: General procedure. Primary aryl amine (2.2 equiv.) in 3 mL ethanol was added into two necked RB flask that contained a solution of dichloro- glyoxime (0.393 g, 2.5 mmol) in 3 mL ethanol (-10 °C). After tri- ethylamine was added, the reaction was allowed to proceed with continued stirring of the solution at room temperature by the time TLC showed the absence of the starting materials (3-4 hours). The resultant solid was gathered by vacuum filtration to give the prod- ucts ( 3a-m ).

Reference： [1]Bayrak, Nilüfer; Mataracı-Kara, Emel; Ozbek-Celik, Berna; Tuyun, Amaç Fatih; Yıldırım, Hatice; Yıldız, Mahmut [Journal of Molecular Structure, 2021, vol. 1242]

83
[ 286-20-4 ]
[ 643-28-7 ]
trans-2-[(2-isopropylphenyl)selanyl]cyclohexan-1-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With selenium; n-Butyl nitrite; lithium tert-butoxide In dimethyl sulfoxide at 120℃; for 24h; Schlenk technique; stereoselective reaction;	β-Hydroxy Aryl Selenides 3; General Procedure General procedure: A Schlenk tube equipped with a stir bar was charged with arylamine 1 (0.3 mmol), Se (71.1 mg, 0.9 mmol), epoxide 2 (1.5 mmol), n-BuONO (61.9 mg, 0.6 mmol), and t-BuOLi (72.0 mg, 0.9 mmol), then anhyd DMSO (3 mL) was added to the Schlenk tube. The reaction mixture was stirred under air at 120 °C in an oil bath for 24 h. After cooling down, the mixture was diluted with Et2O (10 mL), filtered through a pad of silica gel, and concentrated under reduced pressure. The residue was then purified by flash chromatography on silica gel to provide the corresponding product.

Reference： [1]Wang, Hongwei; Li, Hongchen; Bai, Yalong; Hei, Yanling; Chen, Junwei; Yu, Guoqi; Zhou, Yun-Bing [Synthesis, 2021, vol. 53, # 19, p. 3621 - 3629]

84
[ 6541-19-1 ]
[ 643-28-7 ]
7-chloro-6-(2-isopropylphenyl)amino-5,8-quinolinequinone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%	Stage #1: 6,7-dichloroquinoline-5,8-dione With cerium(III) chloride heptahydrate In ethanol at 20℃; for 1h; Stage #2: 2-isopropylaniline In ethanol Reflux; regioselective reaction;	4.3. General procedure for the synthesis of the amino substituted quinolinequinones (AQQ1-19) General procedure: A suspension of the 2 (0.285g, 1.25mmol) and CeCl3.7H2O (0.512g, 1.375mmol, 1.1 equiv) in ethanol was stirred at room temperature for 1h. Then, a suspension of the corresponding amines (1.375mmol, 1.1 equiv) in ethanol was added to that solution and refluxed for 3-6h until consumption of the 2. The reaction mixture was cooled to room temperature. After evaporation of the solvent, the residue was dissolved with CH2Cl2 (50mL), and the solution was washed sequentially with water (3 x 30mL). The organic layer was dried over anhydrous CaCl2, filtered, and concentrated under reduced pressure, and the residue was purified by means of column chromatography on silica gel to give the corresponding AQQ.

Reference： [1]Ciftci, Halil I.; Fujita, Mikako; Otsuka, Masami; Sever, Belgin; Tateishi, Hiroshi; Bayrak, Nilüfer; Tuyun, Amaç Fatih; Yıldırım, Hatice; Yıldız, Mahmut [Chemico-Biological Interactions, 2021, vol. 345]

85
[ 75-77-4 ]
[ 643-28-7 ]
C₁₂H₂₁NSi [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	Stage #1: 2-isopropylaniline With n-butyllithium In diethyl ether; hexane at -25 - 20℃; for 0.666667h; Inert atmosphere; Stage #2: chloro-trimethyl-silane In diethyl ether; hexane at -25℃; Inert atmosphere;
	Stage #1: 2-isopropylaniline With n-butyllithium In diethyl ether; hexane at -78℃; for 0.333333h; Inert atmosphere; Schlenk technique; Stage #2: chloro-trimethyl-silane In diethyl ether; hexane at -78℃; for 0.5h; Inert atmosphere; Schlenk technique;

Reference： [1]Grimme, Stefan; Kooij, Bastiaan; Lin, Jack H.; Qu, Zheng-Wang; Stephan, Douglas W.; Wang, Tongtong; Xu, Maotong [Angewandte Chemie - International Edition, 2021, vol. 60, # 31, p. 16965 - 16969][Angew. Chem., 2021, vol. 133, # 31, p. 17102 - 17106]
[2]Davies, Thomas Q.; Murphy, John J.; Dousset, Maxime; Fürstner, Alois [Journal of the American Chemical Society, 2021, vol. 143, # 34, p. 13489 - 13494]

86
C₁₃H₇FO₃ [ No CAS ]
[ 643-28-7 ]
C₃₁H₂₉FN₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With toluene-4-sulfonic acid In toluene at 120℃; for 48h;	2-17 Example 2-17 Synthesis of Naphthofuran Diimine L55 The compound T5 (4 mmol, 0.920 g) and 2-isopropylaniline (10 mmol, 1.351 g) used as reactants, and p-toluenesulfonic acid (50 mg) used as a catalyst, were refluxed with 100 mL of toluene for 48 h at 120° C. After the reaction was completed, the solvent was removed and the residue was purified on a silica gel column with a mixed solvent of petroleum ether and ethyl acetate (50:1, v/v). The fractions were tested by silica gel plates and the second fraction was collected removing the solvent to give a yellow solid with a yield of 63%. The NMR data of the product were as follows. 1H NMR (400 MHz, CDCl3, δ, ppm): 7.83-7.99 (m, 2H), 7.55 (t, 2H), 7.06-7.32 (m, 8H), 2.88 (s, 1H), 2.01 (s, 3H), 1.18 (d, 6H).

Reference： [1]Current Patent Assignee: LIAO NING OXIRANCHEM, INC. - US2021/395283, 2021, A1 Location in patent: Paragraph 0130-0131

87
[ 32315-10-9 ]
(S)-5-phenyl-2-(pyrrolidin-2-yl)thiazole [ No CAS ]
[ 643-28-7 ]
(S)-N-(2-isopropylphenyl)-2-(5-phenylthiazol-2-yl)pyrrolidine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68.9%	Stage #1: bis(trichloromethyl) carbonate; 2-isopropylaniline With dmap In dichloromethane for 0.5h; Inert atmosphere; Stage #2: (S)-5-phenyl-2-(pyrrolidin-2-yl)thiazole In dichloromethane for 12h; Inert atmosphere;	4.2.9 General procedure for the preparation of 7 General procedure: The solution of substituted aniline (3.138mmol) in dry CH2Cl2 (20mL) was added dropwise to a stirred solution of triphosgene (317mg, 1.070mmol) in CH2Cl2 (20mL) under nitrogen. Then 4-dimethylaminopyridine (1.153g, 9.414mmol) was added to the mixture. The reaction mixture was stirred for 30min, followed by added solution of intermediate 14 in CH2Cl2 (20mL) and reacted overnight (12h). Water (2mL) was added to stop the reaction, the reaction solution was washed with brine (30mL×3), and the aqueous phase was extracted with CH2Cl2 (30mL×2). The combined organic layer was dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (CH2Cl2: MeOH=80:1) to obtain 7a-aa.
68.9%	Stage #1: bis(trichloromethyl) carbonate; 2-isopropylaniline With dmap In dichloromethane for 0.5h; Inert atmosphere; Stage #2: (S)-5-phenyl-2-(pyrrolidin-2-yl)thiazole In dichloromethane for 12h; Inert atmosphere;	4.2.9 General procedure for the preparation of 7 General procedure: The solution of substituted aniline (3.138mmol) in dry CH2Cl2 (20mL) was added dropwise to a stirred solution of triphosgene (317mg, 1.070mmol) in CH2Cl2 (20mL) under nitrogen. Then 4-dimethylaminopyridine (1.153g, 9.414mmol) was added to the mixture. The reaction mixture was stirred for 30min, followed by added solution of intermediate 14 in CH2Cl2 (20mL) and reacted overnight (12h). Water (2mL) was added to stop the reaction, the reaction solution was washed with brine (30mL×3), and the aqueous phase was extracted with CH2Cl2 (30mL×2). The combined organic layer was dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (CH2Cl2: MeOH=80:1) to obtain 7a-aa.

88
[ 1147550-11-5 ]
[ 643-28-7 ]
2-isopropyl-4-thiocyanatoaniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With N,N,N-trimethylbenzenemethanaminium dichloroiodate In lithium hydroxide monohydrate; dimethyl sulfoxide at 70℃; for 1h;	General Procedure General procedure: To a stirred solution of anilines 14a-g' or other substrates (20a-d; 22a-b) (0.27-0.47 mmol), ammonium thiocyanate (1.1 equiv) in 9:1 DMSO:H2O (3.4-6.0 mL; 80 mM final concentration), was added benzyltrimethylammonium dichloroiodate (1.2 equiv). The reaction mixture was heated at 70°C for 1 hour, then allowed to cool to ambient temperature. H2O (25 mL) was added. The mixture was diluted using ethyl acetate, and the organic layer was separated. The aqueous layer was partitioned with EtOAc (2 x 20 mL) and the combined organic layers were washed with 10% aqueous sodium dithionite (2 x 20 mL), followed by saturated sodium bicarbonate solution (2 x 20 mL) and then water (2 X 20 mL). The organic layer was dried over anhydrous magnesium sulfate and the solvents were evaporated. The crude product was then purified using flash chromatography (EtOAc/Hexanes) to give pure 15a-g', 21a-d, and 23a-b.

Reference： [1]Dass, Reuben; Peterson, Matt A.; Singleton, Justin D. [Tetrahedron Letters, 2022]

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P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 643-28-7 ] {[proInfo.proName]}

Quality Control of [ 643-28-7 ]

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Product Details of [ 643-28-7 ]

Calculated chemistry of [ 643-28-7 ]

Physicochemical Properties

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Lipophilicity

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Water Solubility

Medicinal Chemistry

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Application In Synthesis of [ 643-28-7 ]

[ 643-28-7 ] Synthesis Path-Upstream 1~10

[ 643-28-7 ] Synthesis Path-Downstream 1~88

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Aryls

Amines

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[ 643-28-7 ]