[ CAS No. 445-03-4 ] {[proInfo.proName]}

Name: 445-03-4|4-Chloro-2-(trifluoromethyl)aniline|98%
Brand: Ambeed
SKU: A356340
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2D 3D

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Quality Control of [ 445-03-4 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 445-03-4 ]

SDS Specification

Alternatived Products of [ 445-03-4 ]

Product Details of [ 445-03-4 ]

CAS No. :	445-03-4	MDL No. :	MFCD00007841
Formula :	C₇H₅ClF₃N	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	CVINWVPRKDIGLL-UHFFFAOYSA-N
M.W :	195.57	Pubchem ID :	67961
Synonyms :

Calculated chemistry of [ 445-03-4 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.14
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	40.86
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) :	-5.58 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.79
Log Po/w (XLOGP3) :	2.69
Log Po/w (WLOGP) :	4.1
Log Po/w (MLOGP) :	3.15
Log Po/w (SILICOS-IT) :	2.77
Consensus Log Po/w :	2.9

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.05
Solubility :	0.174 mg/ml ; 0.000889 mol/l
Class :	Soluble
Log S (Ali) :	-2.89
Solubility :	0.253 mg/ml ; 0.00129 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.54
Solubility :	0.0558 mg/ml ; 0.000285 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.27

Safety of [ 445-03-4 ]

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

Application In Synthesis of [ 445-03-4 ]

* 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 [ 445-03-4 ]
Downstream synthetic route of [ 445-03-4 ]

[ 445-03-4 ] Synthesis Path-Upstream 1~15

1
[ 445-03-4 ]
[ 53903-51-8 ]

Yield	Reaction Conditions	Operation in experiment
23%	Stage #1: With sulfuric acid; sodium nitrite In water at 0℃; for 3 h; Stage #2: With urea In water for 1.16667 h; Heating / reflux	Add a solution of NaNO2 (0. 458 g, 6.63 mmol) in water (2 mL) to a cool (0°C) mixture of 4- chloro-2-trifluoromethyl-aniline (1.08 g, 5.52 mmol) in 33percent H2SO4 (40 mL). After 3 hours, add urea (0.100 g, 1.67 mmol) and stir for 10 minutes. Add this reaction mixture to 100 mL of refluxing 33percent His04 and heat at reflux'for 1 hour, before cooling to ambient temperature. Extract the mixture with EtOAc. Wash the organic extracts with water and aqueous saturated sodium chloride, dry over anhydrous Na2S04, filter, and concentrate in vacuo. Purify on silica gel eluting with 20percent EtOAc/hexanes to give 4-chloro-2-trifluoromethyl-phenol (0.245 g, 23percent). Mass spectrum (ion spray): m/z = 195 (M-1), lH NMR (CDC13) 6 7.49 (d, 1H), 7. 38 (dd, 1H), 6.91 (d, 1H), 5.44 (brs, 1H).

Reference： [1] Patent: WO2005/92835, 2005, A1, . Location in patent: Page/Page column 37

2
[ 887144-94-7 ]
[ 106-47-8 ]
[ 445-03-4 ]

Yield	Reaction Conditions	Operation in experiment
68%	With potassium carbonate; nickel(II) hydroxide In dimethyl sulfoxide at 35℃; for 2 h;	In the preparation method of the trifluoromethyl aromatic amine of the present embodiment, the aromatic amine is p-chloroaniline, and other reactions and post-treatment processes are the same as in the embodiment 28. The preparation method of the trifluoromethyl aromatic amine of the present embodiment, the aromatic amine is aniline, and the nickel compound is nickel hydroxide.The base is potassium carbonate, and the reaction process parameters are: 1-trifluoromethyl-1,2-phenyliodo-3(H)-one (0.5 mmol, 1.0 eq).Aromatic amine (1.5 mmol, 3.0 eq), nickel hydroxide 10 molpercent, potassium carbonate (1.5 mmol, 3.0 eq),DMSO (2 mL) was reacted at 35 ° C for 2 h, and the other reactions and workup procedures were the same as in Example 1.

Reference： [1] Organic Letters, 2018, vol. 20, # 13, p. 3732 - 3735
[2] Patent: CN108503552, 2018, A, . Location in patent: Paragraph 0190-0194
[3] Organic Letters, 2014, vol. 16, # 6, p. 1768 - 1771

3
[ 2314-97-8 ]
[ 106-47-8 ]
[ 445-03-4 ]

Yield	Reaction Conditions	Operation in experiment
89%	With fac-tris(2-phenylpyridinato-N,C₂')iridium(III); potassium carbonate In 1,2-dichloro-ethane at 20℃; for 24 h; Inert atmosphere; Schlenk technique; Irradiation	General procedure: A 25 mL of Schlenk tube equipped with a magnetic stir bar were charged with aniline (1.2 mmol, 3.0 equiv) or heterocycles (0.8 mmol, 2.0 equiv), K2CO3 (0.8 mmol, 2.0 equiv) and fac-Ir(ppy)3 (2.6 mg, 0.004 mmol, 1 mol percent), under air. The vessel was evacuated and backfilled with Ar (3 times), CF3I stock solution (0.56 mL, 0.71 mmol/mL in 1,2-chloroethane or 0.36 mL, 1.11 mmol/mL in DMSO, 1.0 equiv), anhydrous 1,2-dichloroethane (3 mL) were then added. The tube was screw capped and stirred at room temperature under irradiation of blue LEDs (12 W) for 24 hours. The reaction mixture was filtered through a pad of Celite and washed with ethyl acetate (3×5 mL). The filtrate was concentrated. The residue was subjected to column chromatography on silica gel to afford the pure product.

Reference： [1] Tetrahedron Letters, 2017, vol. 58, # 41, p. 3939 - 3941

4
[ 887144-94-7 ]
[ 106-47-8 ]
[ 1335135-19-7 ]
[ 445-03-4 ]

Reference： [1] Organic Letters, 2014, vol. 16, # 6, p. 1768 - 1771

5
[ 88-17-5 ]
[ 445-03-4 ]

Reference： [1] Beilstein Journal of Organic Chemistry, 2012, vol. 8, p. 744 - 748
[2] Journal of Organic Chemistry, 2017, vol. 82, # 14, p. 7529 - 7537

6
[ 112359-25-8 ]
[ 106-47-8 ]
[ 445-03-4 ]

Reference： [1] Organic Letters, 2014, vol. 16, # 6, p. 1768 - 1771

7
[ 887144-97-0 ]
[ 106-47-8 ]
[ 445-03-4 ]

Reference： [1] Organic Letters, 2014, vol. 16, # 6, p. 1768 - 1771

8
[ 2926-29-6 ]
[ 106-47-8 ]
[ 445-03-4 ]

Reference： [1] Journal of Organic Chemistry, 2014, vol. 79, # 19, p. 8984 - 8989
[2] Organic Letters, 2014, vol. 16, # 6, p. 1768 - 1771

9
[ 75-63-8 ]
[ 106-47-8 ]
[ 445-03-4 ]

Reference： [1] Angewandte Chemie - International Edition, 2016, vol. 55, # 8, p. 2782 - 2786[2] Angew. Chem., 2016, vol. 128, # 8, p. 2832 - 2836,5

10
[ 887144-94-7 ]
[ 74383-34-9 ]
[ 445-03-4 ]
[ 1573118-18-9 ]

Reference： [1] Organic Letters, 2014, vol. 16, # 6, p. 1768 - 1771

11
[ 887144-94-7 ]
[ 35749-94-1 ]
[ 106-47-8 ]
[ 445-03-4 ]
[ 1573118-18-9 ]

Reference： [1] Organic Letters, 2014, vol. 16, # 6, p. 1768 - 1771

12
[ 14547-72-9 ]
[ 445-03-4 ]

Reference： [1] ChemCatChem, 2018, vol. 10, # 5, p. 965 - 970

13
[ 436-20-4 ]
[ 445-03-4 ]

Reference： [1] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 25, p. 119
[2] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 25, p. 119
[3] Patent: US2093115, 1936, ,

14
[ 118-83-2 ]
[ 445-03-4 ]

Reference： [1] Journal of the Chemical Society, 1949, p. 3016,3019

15
[ 393-11-3 ]
[ 445-03-4 ]

Reference： [1] Journal of the Chemical Society, 1949, p. 3016,3019

[ 445-03-4 ] Synthesis Path-Downstream 1~88

1
[ 392-95-0 ]
[ 445-03-4 ]
[ 57729-87-0 ]

Reference： [1]Patent: AT339089,1977,
Patent: DE2509416,1975,
Chem.Abstr.,1976,vol. 84

2
[ 2401-85-6 ]
[ 445-03-4 ]
[ 68105-73-7 ]

Reference： [1]Patent: DE2708440,1978,
Chem.Abstr.,1978,vol. 89

3
[ 445-03-4 ]
[ 654-55-7 ]
[ 72773-26-3 ]

Reference： [1]Patent: DE2815290,1979,
Chem.Abstr.,1980,vol. 92

4
[ 445-03-4 ]
[ 18904-34-2 ]

Reference： [1]Patent: FR1481052,1967,
Chem.Abstr.,1968,vol. 69

5
[ 445-03-4 ]
[ 27738-96-1 ]
[ 35631-27-7 ]
[ 39886-30-1 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1972,vol. 765,p. 78 - 93

6
[ 445-03-4 ]
[ 107-91-5 ]
[ 58140-13-9 ]

Reference： [1]Patent: CH604507,1978,
Patent: DE2460255,1975,
Chem.Abstr.,1976,vol. 84

7
[ 445-03-4 ]
[ 32961-64-1 ]
[ 32935-40-3 ]

Reference： [1]Chemische Berichte,1972,vol. 105,p. 137 - 149

8
[ 445-03-4 ]
[ 32961-64-1 ]
[ 35566-96-2 ]

Reference： [1]Chemische Berichte,1972,vol. 105,p. 137 - 149

9
[ 58853-55-7 ]
[ 445-03-4 ]
2-<(2-Trifluormethyl-4-chlorphenyl)hydrazono>bicyclo<4.4.1>undeca-3,6,8,10-tetraen-5-on [ No CAS ]

Reference： [1]Helvetica Chimica Acta,1983,vol. 66,p. 2369 - 2376

10
[ 349-88-2 ]
[ 445-03-4 ]
N-(4-Chloro-2-trifluoromethyl-phenyl)-4-fluoro-benzenesulfonamide [ No CAS ]

Reference： [1]Farmaco, Edizione Scientifica,1984,vol. 39,p. 514 - 523

11
[ 445-03-4 ]
[ 4895-65-2 ]
[ 76616-18-7 ]

Reference： [1]Liebigs Annalen der Chemie,1980,p. 1651 - 1658

12
[ 445-03-4 ]
4-Chloro-2-trifluoromethyl-benzenediazonium; chloride [ No CAS ]

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1984,vol. 23,p. 1243 - 1257

13
[ 445-03-4 ]
[ 76616-06-3 ]

Reference： [1]Liebigs Annalen der Chemie,1980,p. 1651 - 1658

14
[ 445-03-4 ]
[ 403-43-0 ]
N-(4-Chloro-2-trifluoromethyl-phenyl)-4-fluoro-benzamide [ No CAS ]

Reference： [1]Farmaco, Edizione Scientifica,1986,vol. 41,p. 168 - 174

15
[ 445-03-4 ]
[ 4083-64-1 ]
[ 128924-39-0 ]

Reference： [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 2393 - 2407

16
[ 445-03-4 ]
[ 93-08-3 ]
(4-Chloro-2-trifluoromethyl-phenyl)-[1-naphthalen-2-yl-eth-(E)-ylidene]-amine [ No CAS ]

Reference： [1]Acta poloniae pharmaceutica,2004,vol. 61 Suppl,p. 70 - 72

17
2,5-bis-[4-(5-oxo-2-trifluoromethyl-4,5-dihydro-oxazol-4-yl)-phenoxymethyl]-benzoyl chloride [ No CAS ]
[ 445-03-4 ]
N-(4-chloro-2-trifluoromethyl-phenyl)-2,5-bis-[4-(5-oxo-2-trifluoromethyl-4,5-dihydro-oxazol-4-yl)-phenoxymethyl]-benzamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 3289 - 3298

18
[ 4053-08-1 ]
[ 445-03-4 ]
[ 905279-52-9 ]

Reference： [1]Macromolecules,2006,vol. 39,p. 6425 - 6432

19
[ 445-03-4 ]
[ 81-30-1 ]
[ 892496-63-8 ]

Reference： [1]Macromolecules,2006,vol. 39,p. 6425 - 6432

20
[ 445-03-4 ]
[ 4755-77-5 ]
[ 126991-37-5 ]

Yield	Reaction Conditions	Operation in experiment
> 90%	With triethylamine; In tetrahydrofuran; at 0 - 20℃;Inert atmosphere;	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 (84percent) of 27 as a colorless crystalline solid.
86%	With triethylamine; In dichloromethane; at 15℃; for 16h;	Compound 60-a (6.00 g, 30.68 mmol, 4.32 mL, 1.00 eq) was dissolved in dichloromethane (80.00 mL), and triethylamine (6.21 g, 61.36 mmol, 8.51 mL, 2.00 eq) and compound 1-b (5.03 g, 36.82 mmol, 4.12 mL, 1.20 eq) were successively added thereto. The reaction solution was stirred at 15°C for 16 hours. After the reaction was completed, water (250 mL) and dichloromethane (250 mL) were added for extraction. The organic phase was washed with hydrochloric acid solution (1 N, 250 mL) and brine (250 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to give a crude product. The crude product was subjected to column chromatography (petroleum ether : ethyl acetate = 1:0?4:1) to give the product of compound 60-b (8.00 g, yield: 86percent) as a pale yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) delta=9.34 (br. s., 1H), 8.37 (d, J=9.03 Hz, 1H), 7.65 (d, J=2.01 Hz, 1H), 7.59 (d, J=9.03 Hz, 1H), 4.46 (q, J=7.28 Hz, 2H), 1.45 (t, J=7.03 Hz, 3H).

Reference： [1]Synthesis,2006,p. 807 - 812
[2]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 91 - 101
[3]Patent: EP3456711,2019,A1 .Location in patent: Paragraph 0419; 0420

21
[ 445-03-4 ]
[ 130860-69-4 ]
3-[(4-chloro-2-(trifluoromethyl)-phenylamino)(phenyl)methyl]-4-methylenecyclopentane-1,1-dicarboxylic acid dimethyl ester [ No CAS ]

Reference： [1]Organic Letters,2007,vol. 9,p. 4049 - 4052

22
[ 445-03-4 ]
[ 135755-23-6 ]
[(benzo[1,3]dioxol-5-yl)(4-methylene-tetrahydro-furan-3-yl)methyl]-(4-chloro-2-(trifluoromethyl)phenyl)-amine [ No CAS ]

Reference： [1]Organic Letters,2007,vol. 9,p. 4049 - 4052

23
[ 445-03-4 ]
[ 403-42-9 ]
N-[2-(dimethylamino)ethyl]-6-chloro-2-(4-fluorophenyl)quinolin-4-amine [ No CAS ]

Reference： [1]Heterocyclic Communications,2007,vol. 13,p. 9 - 12

24
[ 2142-68-9 ]
[ 445-03-4 ]
N-[2-(dimethylamino)ethyl]-6-chloro-2-[(2-chloro)phenyl]quinolin-4-amine [ No CAS ]

Reference： [1]Heterocyclic Communications,2007,vol. 13,p. 9 - 12

25
[ 445-03-4 ]
N-(4-chloro-2-trifluoromethyl-phenyl)-N'-(2,2,6,6-tetramethyl-piperidin-4-yl)-oxalamide [ No CAS ]

Reference： [1]Synthesis,2006,p. 807 - 812

26
[ 445-03-4 ]
N'-(6-chloro-2-naphthalen-2-yl-quinolin-4-yl)-N,N-dimethyl-ethane-1,2-diamine [ No CAS ]

Reference： [1]Acta poloniae pharmaceutica,2004,vol. 61 Suppl,p. 70 - 72

27
[ 445-03-4 ]
6-chloro-4-(4-methyl-piperazin-1-yl)-2-naphthalen-2-yl-quinoline [ No CAS ]

Reference： [1]Acta poloniae pharmaceutica,2004,vol. 61 Suppl,p. 70 - 72

28
[ 445-03-4 ]
2-(4-chloro-2-trifluoromethyl-phenylamino)-N-(2-pyridin-4-yl-ethyl)-2-o-tolyl-acetamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 2426 - 2429

29
[ 445-03-4 ]
6-Chloro-4-(4-methyl-piperazin-1-yl)-2-[2-(4-methyl-piperazin-1-yl)-phenyl]-quinoline [ No CAS ]

Reference： [1]Tetrahedron,1996,vol. 52,p. 3273 - 3282

30
[ 445-03-4 ]
[ 156425-10-4 ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 4367 - 4379
[2]Patent: US5514680,1996,A

31
[ 445-03-4 ]
[ 62924-50-9 ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 4367 - 4379
[2]Patent: US5514680,1996,A

32
[ 445-03-4 ]
[ 172216-01-2 ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 4367 - 4379
[2]Patent: US5514680,1996,A

33
[ 445-03-4 ]
[ 172215-95-1 ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 4367 - 4379
[2]Patent: US5514680,1996,A

34
[ 445-03-4 ]
[ 179062-21-6 ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 4367 - 4379

35
[ 445-03-4 ]
6,7-Dichloro-5-trifluoromethyl-1,4-dihydro-quinoxaline-2,3-dione [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 4367 - 4379

36
[ 445-03-4 ]
[ 172216-08-9 ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 4367 - 4379
[2]Patent: US5514680,1996,A

37
[ 445-03-4 ]
4-Amino-N-(4-chloro-2-trifluoromethyl-phenyl)-benzenesulfonamide [ No CAS ]

Reference： [1]Il Farmaco,1994,vol. 49,p. 197 - 200

38
[ 445-03-4 ]
[ 1513-34-4 ]

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1984,vol. 23,p. 1243 - 1257

39
[ 445-03-4 ]
[ 96423-47-1 ]

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1984,vol. 23,p. 1243 - 1257

40
[ 445-03-4 ]
[ 24095-90-7 ]

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1984,vol. 23,p. 1243 - 1257

41
[ 393-11-3 ]
[ 445-03-4 ]

Reference： [1]Journal of the Chemical Society,1949,p. 3016,3019

42
[ 445-03-4 ]
[ 344-53-6 ]

Yield	Reaction Conditions	Operation in experiment
1.123 g (91.7%)	In acetic anhydride;	A. 2-Acetamido-5-chlorobenzotrifluoride A solution of 2-amino-5-chlorobenzotrifluoride (1.01 g, 5.16 mmol, Aldrich) in acetic anhydride (5 mL) was stirred at room temperature for 12 h to produce white needle precipitate. It was filtered to give 1.123 g (91.7percent) of 2-acetamido-5-chlorobenzotrifluoride. 1 H NMR (CDCl3): delta2.214 (s, 3H); 7.359 (br, 1H); 7.512 (d, 1H, J=9 Hz), 7.581 (s, 1H); 7.163 (d, 1H, J=8.4 Hz).

Reference： [1]Patent: US5514680,1996,A

43
[ 19602-82-5 ]
[ 445-03-4 ]
[ 177786-21-9 ]

Yield	Reaction Conditions	Operation in experiment
	In pyridine; dichloromethane;	EXAMPLE 82 2,2'-Dithiobis[N-[4-chloro-3-(trifluoromethyl)phenyl]benzamide] This compound was prepared according to the general method of Example 77 using 2,2'-dithiobisbenzoyl chloride (2.00 g, 5.83 mmol) in 50 mL of dichloromethane and 2-amino-5-chlorobenzotrifluoride (2.30 g, 11.6 mmol) in 18 mL of pyridine. The crude product was recrystallized from ethyl ether-hexanes to yield 0.59 g of the title compound, mp 129°-131° C.

Reference： [1]Patent: US5734081,1998,A

44
[ 445-03-4 ]
[ 126991-37-5 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In tetrahydrofuran;	d. N-ethoxalyl-4-chloro-2-trifluoromethylaniline A mixture of 2-amino-5-chlorobenzotrifluoride (14.4 ml, 0.1 mol) and triethylamine (14.0 ml, 0.1 mol) was dissolved in dry tetrahydrofuran, THF (250 ml). To this solution was added with stirring a solution of ethoxalyl chloride in THF (50 ml). After completion of the addition (30 min.) the mixture was stirred at ambient temperature for 3 h, whereafter the precipitated triethylammonium chloride was filtered off, and the filtrate was evaporated in vacuo. This left the crude title compound (24 g) as pale crystals. M.p. 55°-58° C.

Reference： [1]Patent: US5075304,1991,A

45
[ 445-03-4 ]
[ 56-37-1 ]
[ 88-17-5 ]

Yield	Reaction Conditions	Operation in experiment
9.7 parts (60.3%)	With sodium hydroxide; sodium formate;palladium on charcoal; In water;	EXAMPLE 2 To a solution of sodium formate (38 parts) in water (100 parts) are added sodium hydroxide liquor (32percent; 13.5 parts), benzyl triethylammonium chloride (1.0 parts), 3percent palladium on charcoal (50percent paste; 6.0 parts) and 5-chloro-2-aminobenzotrifluoride (19.6 parts). The mixture is stirred rapidly at the boil under reflux for 4 hours and then steam distilled. The distillate is extracted with chloroform (2 * 50 parts), the extract dried over magnesium sulphate and then the solvent removed to give 9.7 parts (60.3percent) of 2-aminobenzotrifluoride. When the above procedure is repeated in absence of benzyltriethylammonium chloride the yield of 2-aminobenzotrifluoride falls to 23percent.

Reference： [1]Patent: US4022795,1977,A

46
[ 321-14-2 ]
[ 445-03-4 ]
N-[4-chloro-2-(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21.5%		Example 105 5-Chloro-N-[4-chloro-2-(trifluoromethyl)phenyl]-2-hydroxybenzamide (Comopund No. 105). Using 5-chlorosalicylic acid and <strong>[445-03-4]4-chloro-2-(trifluoromethyl)aniline</strong> as the raw materials, the same operation as the example 16 gave the title compound. Yield: 21.5percent. 1H-NMR(DMSO-d6): delta 7.07(1H, d, J=8.7Hz), 7.52(1H, dd, J=8.7, 2.7Hz), 7.80-7.85(2H, m), 7.97(1H, d, J=2.7Hz), 8.26(1H, d, J=8.4Hz), 10.80(1H, s), 12.26(1H, s).

Reference： [1]Patent: EP1352650,2003,A1

47
[ 445-03-4 ]
[ 1020842-00-5 ]
[ 925234-67-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 4538 - 4544

48
[ 302-17-0 ]
[ 445-03-4 ]
N-(4-chloro-2-(trifluoromethyl)phenyl)-2-(hydroxyimino)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30%	With hydrogenchloride; hydroxylamine hydrochloride; sodium sulfate; In ethanol; water;Heating / reflux;	The methodology reported by L. Kuyper et al. (see J. Med. Chem. 2001, 44: 4339) was used. In a 1 L round-bottom flask, anhydrous sodium sulfate (85 g) was dissolved in 230 mL of boiling water, with stirring. A hot solution of <strong>[445-03-4]4-chloro-2-(trifluoromethyl)aniline</strong> (6.5 g, 33 mmol) in 50 mL of 1 M hydrochloric acid, 2 mL of concentrated hydrochloric acid and 30 mL of ethanol was added. An additional 60 mL of ethanol was added. Chloral hydrate (6.6 g, 40 mmol) was added, followed by hydroxylamine hydrochloride (7.6 g, 0.11 mol) in 30 mL of water. The mixture was heated at reflux temperature and ethanol was added until the aniline was dissolved again. Heating was continued for 3 hours. With the flask open to atmosphere, the reaction mixture was heated at reflux temperature overnight. The reaction mixture was cooled to 0° C. and the off-white precipitate was collected by filtration. This precipitate, which contained a large amount of sodium sulfate, was taken up in 300 mL of water, stirred at room temperature for 1 hour, filtered, taken up in 200 mL of water, stirred for 30 minutes, filtered, and dried under vacuum to give an off-white powder (intermediate 81, 2.65 g, 30percent yield). 1H NMR (400 MHz, DMSO-d6) delta 7.66 (s, 1H), 7.76-7.86 (m, 3H), 9.63 (s, 1H), 12.44 (s, 1H).

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 6003 - 6017
[2]Patent: US2008/255192,2008,A1 .Location in patent: Page/Page column 24-25

49
[ 828266-00-8 ]
[ 445-03-4 ]
[ 850039-94-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 8516 - 8525

50
[ 110-91-8 ]
2-[6-(bromomethyl)-7-chloro-2-oxo-4-phenyl-2H-chromen-3-yl]acetic acid [ No CAS ]
[ 445-03-4 ]
2-[7-chloro-6-{(morpholin-4-yl)methyl}-2-oxo-4-phenyl-2H-chromen-3-yl]-N-(4-chloro-2-trifluoromethylphenyl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%		A solution of 2-[6-(bromomethyl)-7-chloro-2-oxo-4-phenyl-2H-chromen-3-yl]acetic acid (0.20 g) in THF (5 ml) was combined with DMF (1 drop) and oxalyl chloride (86 ml), and stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure to obtain the residue, which was dissolved in THF (3 ml), and added dropwise to a suspension of 4-chloro-2-trifluoromethylaniline (69 ml) and sodium hydride (60percent, in oil) in THF (2 ml) at 0° C. After stirring at room temperature for 12 hours, the reaction solution was combined with water, and the product was extracted with ethyl acetate. The extract was washed with a 1 N solution of hydrochloric acid followed by a saturated aqueous solution of sodium chloride, a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride, and after drying over magnesium sulfate, the solvent was distilled off under reduced pressure. The resultant residue was dissolved in THF (2 ml), combined with morpholine (0.21 ml), and stirred for 3 days. The reaction solution was concentrated under reduced pressure, and the resultant residue was dissolved in ethyl acetate (30 ml), and then washed with a saturated aqueous solution of sodium chloride. After drying over magnesium sulfate, the solvent was distilled off under reduced pressure. The resultant residue was purified by a silica gel column chromatography (eluent: chloroform-methanol-aqueous ammonia=40:1:0.1), and further purified by recrystallization from ethyl acetate to obtain the title compound (112 mg, yield: 57percent). [0676] Melting point: 205-207° C. [0677] NMR (CDCl3) delta: 2.35-2.45 (4H, m), 3.45-3.65 (8H, m), 7.21 (1H, s), 7.30-7.40 (2H, m), 7.45 (1H, s), 7.45-7.65 (5H, m), 8.08 (1H, d, J=9 Hz), 8.24 (1H, brs). [0678] IR(KBr): 1725, 1663, 1530, 1310 cm-1. [0679] Analysis for C29H23N2O4Cl2F3 [0680] Calcd (percent): C:58.90H:3.92 N:4.74 [0681] Found (percent): C:58.90H:3.89 N:4.61

Reference： [1]Patent: US2003/232809,2003,A1 .Location in patent: Page 47-48

51
2-[6-(bromomethyl)-7-chloro-2-oxo-4-phenyl-2H-chromen-3-yl]acetic acid [ No CAS ]
[ 445-03-4 ]
[ 127-09-3 ]
[7-chloro-3-{2-(4-chloro-2-trifluoromethylanilino)-2-oxoethyl}-2-oxo-4-phenyl-2H-chromen-6-yl]methyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%		A solution of 2-[6-(bromomethyl)-7-chloro-2-oxo-4-phenyl-2H-chromen-3-yl]acetic acid (0.30 g) in THF (6 ml) was combined with DMF (1 drop) and oxalyl chloride (130 ml), and stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure to obtain the residue, which was dissolved in THF (3 ml), and added dropwise to a suspension of 4-chloro-2-fluoromethylaniline (104 ml) and sodium hydride (60percent, in oil)(121 mg) in THF (2 ml) at 0° C. After stirring for 1 hour, the reaction solution was combined with water, and the product was extracted with ethyl acetate. The extract was washed with a 1 N solution of hydrochloric acid followed by a saturated aqueous solution of sodium chloride, a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride, and after drying over magnesium sulfate, the solvent was distilled off under reduced pressure. The resultant residue was dissolved in DMF (3 ml), combined with anhydrous sodium acetate (121 mg), and stirred at 60° C. for 3 hours. The reaction solution was combined with water, and the product was extracted with ethyl acetate, and the extract was washed with a saturated aqueous solution of sodium chloride. After drying over magnesium sulfate, the solvent was distilled off under reduced pressure to obtain the residue, which was purified by a silica gel column chromatography (eluent: ethyl acetate-hexane=1:2), and further purified by recrystallization from ethyl acetate to obtain the title compound (126 mg, yield: 45percent). [0701] Melting point: 186-187° C. [0702] NMR (CDCl3) delta: 1.99 (3H, s), 3.49 (2H, s), 5.10 (2H, s), 7.08 (1H, s), 7.30-7.40 (2H, m), 7.45-7.65 (6H, m), 8.08 (1H, d, J=9 Hz), 8.17 (1H, brs). [0703] IR(KBr): 1725, 1663, 1530, 1310 cm-1. [0704] Analysis for C27H18NO5Cl2F3 [0705] Calcd (percent): C:57.46H:3.21 N:2.48 [0706] Found (percent): C:57.20H:3.25 N:2.25

Reference： [1]Patent: US2003/232809,2003,A1 .Location in patent: Page 49

52
[ 2637-34-5 ]
2-[6-(bromomethyl)-7-chloro-2-oxo-4-phenyl-2H-chromen-3-yl]acetic acid [ No CAS ]
[ 445-03-4 ]
2-[7-chloro-2-oxo-4-phenyl-6-[(pyridine-2-ylthio)methyl]-2H-chromen-3-yl]-N-[4-chloro-2-(trifluoromethyl)phenyl]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%		A solution of 2-[6-(bromomethyl)-7-chloro-2-oxo-4-phenyl-2H-chromen-3-yl]acetic acid (0.21 g) in THF (5 ml) was combined with DMF (1 drop) and oxalyl chloride (86 ml), and stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure, and the resultant residue was dissolved in THF (3 ml) and added dropwise to a suspension of 2-chloro-4-trifluoromethylaniline (72 ml) and sodium hydride (60percent, in oil) (23 mg) in THF (2 ml) at 0° C. After stirring at room temperature for 12 hours, the reaction solution was combined with water, and the product was extracted with ethyl acetate. The extract was washed with a 1 N solution of hydrochloric acid followed by a saturated aqueous solution of sodium chloride, a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride, and after drying over magnesium sulfate, the solvent was distilled off under reduced pressure. The resultant residue was dissolved in THF (10 ml), combined with 2-mercaptopyridine (0.088 g) and DBU (0.118 ml), and stirred at room temperature for 24 hours. The reaction solution was combined with water, and extracted with ethyl acetate. The extract was washed with a saturated brine, and then dried over magnesium sulfate, and concentrated under reduced pressure. The resultant residue was recrystallized from ethyl acetate-diisopropyl ether to obtain the title compound as a colorless crystal (205 mg, 65percent). Melting point: 213-215° C.

Reference： [1]Patent: US2003/232809,2003,A1 .Location in patent: Page 58-59

53
2-[6-(bromomethyl)-7-chloro-2-oxo-4-phenyl-2H-chromen-3-yl]acetic acid [ No CAS ]
[ 445-03-4 ]
[ 434333-11-6 ]

Yield	Reaction Conditions	Operation in experiment
		A solution of 2-[6-(bromomethyl)-7-chloro-2-oxo-4-phenyl-2H-chromen-3-yl]acetic acid (1.6 g) in THF (40 ml) was combined with DMF (5 drops) and oxalyl chloride (0.7 ml), and stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure to obtain the residue, which was dissolved in THF (20 ml) and added dropwise to a suspension of 2-chloro-4-trifluoromethylaniline (0.55 ml) and sodium hydride (60percent, in oil) (176 mg) in THF (20 ml) at 0° C. After stirring at room temperature for 12 hours, the reaction solution was combined with water, and the product was extracted with ethyl acetate. The extract was washed with a 1 N solution of hydrochloric acid followed by a saturated aqueous solution of sodium chloride, a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride, and after drying over magnesium sulfate, the solvent was distilled off under reduced pressure. The resultant crude crystal of 2-[6-(bromomethyl)-7-chloro-2-oxo-4-phenyl-2H-chromene-3-yl]-N-(4-chloro-2-trifluoromethylphenyl)acetamide was dissolved in DMF (6 ml), combined with sodium cyanide (0.13 g), and stirred for 3 hours. The reaction solution was combined with water to form a precipitate, which was filtered and washed with water followed by methanol and ether. The precipitate thus obtained was purified by a silica gel column chromatography (eluent: chloroform-ethyl acetate-hexane=5:1:4), and further recrystallized from THF-diisopropyl ether to obtain the title compound (480 mg, yield: 55percent). Melting point: 247-248° C.
		A solution of 2-[6-(bromomethyl)-7-chloro-2-oxo-4-phenyl-2H-chromen-3-yl]acetic acid (0.41 g) in THF (10 ml) was combined with DMF (1 drop) and oxalyl chloride (0.2 ml), and stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure to obtain the residue, which was dissolved in THF (5 ml) and added dropwise to a suspension of 2-chloro-4-trifluoromethylaniline (0.14 ml) and sodium hydride (60percent, in oil) (44 mg) in THF (5 ml) at 0° C. After stirring at room temperature for 12 hours, the reaction solution was combined with water, and the product was extracted with ethyl acetate. The extract was washed with a 1 N solution of hydrochloric acid followed by a saturated aqueous solution of sodium chloride, a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride, and after drying over magnesium sulfate, the solvent was distilled off under reduced pressure. A solution of the resultant crude crystal of 2-[6-(bromomethyl)-7-chloro-2-oxo-4-phenyl-2H-chromen-3-yl]-N-(4-chloro-2-trifluoromethylphenyl)acetamide in DMF (10 ml) was combined with 1-phenyl-piperazine (0.166 g) and potassium carbonate (0.285 g), and stirred at 80° C. for 30 minutes. After cooling, the reaction solution was diluted with ethyl acetate (5 ml), and poured into water (120 ml). The precipitate formed was filtered and washed with water (20 ml) followed by ethanol (10 ml). The crystal filtered was dissolved in THF (6 ml), and then combined with concentrated hydrochloric acid (0.26 ml), and stirred for 20 minutes. The precipitate was filtered, and washed with ethyl acetate to obtain the title compound (491 mg, yield: 70percent). Melting point: 238-239° C.
		A solution of 2-[6-(bromomethyl)-7-chloro-2-oxo-4-phenyl-2H-chromen-3-yl]acetic acid (0.41 g) in THF (10 ml) was combined with DMF (1 drop) and oxalyl chloride (0.2 ml), and stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure to obtain the residue, which was dissolved in THF (5 ml) and added dropwise to a suspension of 2-chloro-4-trifluoromethylaniline (0.14 ml) and sodium hydride (66percent, in oil) (44 mg) in THF (5 ml) at 0° C. After stirring at room temperature for 12 hours, the reaction solution was combined with water, and the product was extracted with ethyl acetate. The extract was washed with a 1 N solution of hydrochloric acid followed by a saturated aqueous solution of sodium chloride, a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride, and after drying over magnesium sulfate, the solvent was distilled off under reduced pressure. A solution of the resultant crude crystal of 2-[6-(bromomethyl)-7-chloro-2-oxo-4-phenyl-2H-chromen-3-yl]-N-(4-chloro-2-trifluoromethylphenyl)acetamide in DMF (10 ml) was combined with 1-phenyl piperazine (0.166 g) and potassium carbonate (0.285 g), and stirred at 80° C. for 30 minutes. After cooling, the reaction solution was diluted with ethyl acetate (5 ml), and poured into water (120 ml). The precipitate formed was filtered, and washed with water (20 ml) followed by ethanol (10 ml). The crystal filtered was dissolved in THF (6 ml), and then combined with concentrated hydrochloric acid (0.26 ml), and stirred for 20 minutes. The precipitate was filtered and washed with ethyl acetate. A suspension of the precipitate filtered in ethanol (10 ml) was combined with a saturated aqueous solution of sodium hydrogen carbonate (30 ml), and stirred for 20 minutes. The precipitate was filtered and washed with water (20 m) followed by ethanol (10 ml). The crystal filtered was dissolved in THF (20 ml), and then dried over magnesium sulfate, and then concentrated under reduced pressure. The resultant residue was recrystallized from THF-ethanol to obtain the title compound as a colorless crystal (0.431 g, yield: 63percent). Melting point: 201-203° C.

Reference： [1]Patent: US2003/232809,2003,A1 .Location in patent: Page 63
[2]Patent: US2003/232809,2003,A1 .Location in patent: Page 64
[3]Patent: US2003/232809,2003,A1 .Location in patent: Page 65

54
2-[6-(bromomethyl)-7-chloro-2-oxo-4-phenyl-2H-chromen-3-yl]acetic acid [ No CAS ]
[ 445-03-4 ]
[ 57260-71-6 ]
2-[7-chloro-2-oxo-4-phenyl-6-(piperazin-1-yl)methyl-2H-chromen-3-yl]-N-[4-chloro-2-(trifluoromethyl)phenyl]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30%		A solution of 2-[6-(bromomethyl)-7-chloro-2-oxo-4-phenyl-2H-chromen-3-yl]acetic acid (0.28 g) in THF (7 ml) was combined with DMF (1 drop) and oxalyl chloride (120 ml), and stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure to obtain the residue, which was dissolved in THF (5 ml) and added dropwise to a suspension of 2-chloro-4-trifluoromethylaniline (101 ml) and sodium hydride (60percent, in oil) (32 mg) in THF (3 ml) at 0° C. After stirring at room temperature for 12 hours, the reaction solution was combined with water, and the product was extracted with ethyl acetate. The extract was washed with a 1 N solution of hydrochloric acid followed by a saturated aqueous solution of sodium chloride, a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride, and after drying over magnesium sulfate, the solvent was distilled off under reduced pressure. The resultant residue was dissolved in THF (10 ml), combined with tert-butyl 1-piperidinecarboxylate (0.191 g) and triethylamine (0.14 ml), and heated under reflux for 5 hours. The reaction solution was combined with water and extracted with ethyl acetate. The extract was washed with a saturated brine, dried over magnesium sulfate, and then concentrated under reduced pressure. The resultant residue was dissolved in acetic acid (10 ml), combined with concentrated hydrochloric acid (10 ml), and then heated under reflux for 30 minutes. The reaction solution was combined with water and extracted with ethyl acetate. The extract was washed with a saturated sodium bicarbonate followed by a saturated brine, dried over magnesium sulfate, and then the extract was concentrated under reduced pressure. The resultant residue was recrystallized from ethyl acetate-diisopropyl ether to obtain the title compound as a colorless crystal (122 mg, 30percent). Melting point: 237-242° C.

Reference： [1]Patent: US2003/232809,2003,A1 .Location in patent: Page 59-60

55
[7-chloro-2-oxo-4-phenyl-6-[(4-phenylpiperazin-1-yl)methyl]-2H-chromen-3-yl]acetic acid [ No CAS ]
[ 445-03-4 ]
[ 391686-69-4 ]

Yield	Reaction Conditions	Operation in experiment
71%		[7-Chloro-2-oxo-4-phenyl-6-[(4-phenylpiperazine-1-yl)methyl]-2H-chromen-3-yl]acetic acid (500 g) was suspended in a mixture solution of THF (5 L) and DMF (5 ml), and cooled to 5° C. or lower with cooling in ice. Thionyl chloride (150 ml) was added dropwise at the same temperature. After completing dropwise addition, the mixture was allowed to warm to room temperature, and stirred at 25 to 30° C. for 5 hours. The reaction solution was combined with toluene (2 L) and concentrated under reduced pressure. The resultant residue was suspended in THF (5 L), combined with <strong>[445-03-4]4-chloro-2-(trifluoromethyl)aniline</strong> (250 g), and refluxed at 80° C. for 5 hours. The reaction solution was cooled to 40° C., and combined with acetone (5 L) and water (2.5 L). The mixture was adjusted to pH 7.6 with 25percent aqueous ammonia, and stirred at 15 to 20° C. for 30 minutes. The crystal precipitated was separated by centrifugal separator, and washed with acetone and water to obtain the title compound (487 g, yield: 71percent). [0816] Melting point: 201-203° C.

Reference： [1]Patent: US2003/232809,2003,A1 .Location in patent: Page 66

56
C₂₇H₂₄ClN₃O₄ [ No CAS ]
[ 445-03-4 ]
2-[7-chloro-2-oxo-6-[(4-phenyl-1-piperazinyl)methyl]-4-(3-pyridinyl)-2H-chromen-3-yl]-N-[4-chloro-2-(trifluoromethyl)phenyl]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21%		A suspension of ethyl 7-chloro-2-oxo-6-[(4-phenyl-1-piperazinyl)methyl]-4-(3-pyridinyl)-2H-chromen-3-yl]acetate (500 mg, 0.97 mmol) in ethanol (10 ml) was combined with a 2 N aqueous solution of sodium hydroxide (1.5 ml), and heated and stirred at 70° C. for 1 hour. After allowing to cool, the mixture was combined with 1 N hydrochloric acid (3 ml), and neutralized with a saturated aqueous solution of sodium hydrogen carbonate. The solvent was distilled off under reduced pressure, and the residue was boiled azeotropically with toluene to remove water. The resultant yellow powder (350 mg) was combined with THF (5 ml), DMF (1 drop) and thionyl chloride (0.22 ml), and stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure, and the residue was combined with THF (15 ml) and 2-amino-5-chlorobenzotrifluoride (0.38 ml, 2.1 mmol), and stirred at 80° C. for 15 hours. After allowing to cool, the mixture was combined with an aqueous solution of ammonium chloride, and extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate, and then the solvent was distilled off under reduced pressure. The resultant residue was purified by a silica gel column chromatography (eluent: hexane-ethyl acetate=1:1), and further recrystallized from ethyl acetate-isopropyl ether to obtain the title compound as a colorless crystal (102 mg, yield: 21percent). Melting point: 214-216° C.

Reference： [1]Patent: US2003/232809,2003,A1 .Location in patent: Page 73-74

57
[ 32315-10-9 ]
[ 445-03-4 ]
[ 16588-69-5 ]

Reference： [1]Journal of Agricultural and Food Chemistry,2007,vol. 55,p. 1364 - 1369

58
[ 445-03-4 ]
[ 485386-83-2 ]
[ 1160929-76-9 ]

Reference： [1]European Journal of Medicinal Chemistry,2009,vol. 44,p. 2711 - 2719

59
[ 1221424-63-0 ]
[ 445-03-4 ]
[ 1221424-96-9 ]

Yield	Reaction Conditions	Operation in experiment
49%	With scandium tris(trifluoromethanesulfonate); at 20℃; for 15h;Neat (no solvent);	(Comparative Example 54); 5- [ (2S) -2-Benzyloxypropyl] -1- [4-chloro-2- (trifluoromethyl) phenyl] -2-ethyl-lH-pyrrole-3-carboxylic acid ethyl esterTo a neat mixture of diketone (2.02 g, 6 mmol) and 2- trifluoromethyl-4-chloroaniline (0.85 mL, 6 mmol) was added Sc(OTf)3 (148 mg, 0.3 mmol) . The reaction was stirred at room temperature for 15 h, and then was evaporated from CH3CN (2 X 10 mL) to remove water. The crude residue was purified by chromatography on silica gel (2percent diethyl ether in 1/1 - hexane/CH2Cl2) to afford the pyrrole product (1.48 g, 49percent) as a pale yellow oil.1H-NMR (400 MHz, CDCl3) delta: 7.77 (IH, m) , 7.51 (0.5H, dd, J = 8.4, 2.0 Hz), 7.45 (0.5H, dd, J = 8.4, 2.0 Hz), 7.33-7.21 (4H, m) , 7.17 (IH, m) , 7.09 (0.5H, d, J = 8.4 Hz) , 6.98 (0.5H, d, J = 8.4), 6.47 (0.5H, s) , 6.45 (0.5H, s) , 4.50 (0.5H, d, J = 12.0 Hz), 4.46 (0.5H, d, J = 11.6 Hz) , 4.37-4.25 (3H, m) , 3.68-3.54 (IH, m) , 3.04-2.93 (IH, m) , 2.66 (0.5H, dd, J = 15.6, 5.6 Hz), 2.42 (0.5H, dd, J = 15.2, 6.0 Hz), 2.26 (0.5H, dd, J = 15.2, 6.8 Hz) , 2.19-2.06 (1.5H, m) , 1.36 (3H, t, J = 7.2 Hz), 1.18 (1.5H, d, J = 6.4 Hz), 1.13 (1.5H, d, J = 6.0 Hz) , 1.00-0.96 (3H, m) .

Reference： [1]Patent: WO2010/42626,2010,A1 .Location in patent: Page/Page column 57

60
[ 79-37-8 ]
[ 445-03-4 ]
C₉H₄Cl₂F₃NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In 1,2-dichloro-ethane; at 100℃; for 16h;	50 mg of an aniline are dissolved in 3 ml of dichloroethane and mixed with 38 mul of oxalyl chloride. The reaction solution is stirred at 100° C. for 16 hours and then concentrated.

Reference： [1]Patent: US2010/261644,2010,A1 .Location in patent: Page/Page column 20

61
potassium 2-oxocycloheptylsulfonate [ No CAS ]
[ 445-03-4 ]
[ 1029797-78-1 ]

Reference： [1]Journal of Agricultural and Food Chemistry,2010,vol. 58,p. 11384 - 11389

62
potassium 2-oxocyclododecylsulfonate [ No CAS ]
[ 445-03-4 ]
[ 1253692-19-1 ]

Reference： [1]Journal of Agricultural and Food Chemistry,2010,vol. 58,p. 11384 - 11389

63
potassium 2-oxocyclododecylsulfonate [ No CAS ]
[ 445-03-4 ]
[ 1253692-85-1 ]

Reference： [1]Journal of Agricultural and Food Chemistry,2010,vol. 58,p. 11384 - 11389

64
[ 1094389-75-9 ]
[ 445-03-4 ]
[ 1253692-11-3 ]

Reference： [1]Journal of Agricultural and Food Chemistry,2010,vol. 58,p. 11384 - 11389

65
[ 1094389-71-5 ]
[ 445-03-4 ]
[ 1253692-18-0 ]

Reference： [1]Journal of Agricultural and Food Chemistry,2010,vol. 58,p. 11384 - 11389

66
[ 1129-30-2 ]
[ 445-03-4 ]
[ 853786-03-5 ]

Reference： [1]Journal of Molecular Catalysis A: Chemical,2011,vol. 340,p. 83 - 88

67
[ 445-03-4 ]
[ 931107-00-5 ]

Yield	Reaction Conditions	Operation in experiment
75%	With isopentyl nitrite; In benzene; at 20℃; for 0.0833333h;	General procedure: 5.1.1.1. Method AA solution of isoamyl nitrite (1.755 g, 15 mmol) in benzene (30 mL) was added drop wise to 4-chloro-2-trifluoromethylaniline (1.956 g, 10 mmol) at room temperature. The reaction mixture was stirred for 5 min and evaporated to dryness under reduced pressure. The residue was treated with petroleum ether (5 mL) and the solid material was filtered off to give 1d in 75percent yield.

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 2971 - 2983

68
[ 445-03-4 ]
[ 1334531-17-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 5207 - 5224

69
[ 445-03-4 ]
[ 1334531-18-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 5207 - 5224

70
[ 445-03-4 ]
(S)-(5-chloro-2-[(2,2-dimethylpropyl)amino]-3-methylphenyl)(2-methoxyphenyl)methanol [ No CAS ]
(R)-(5-chloro-2-[(2,2-dimethylpropyl)amino]-3-methylphenyl)(2-methoxyphenyl)methanol [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 5207 - 5224

71
[ 445-03-4 ]
[ 1334531-19-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 5207 - 5224

72
[ 445-03-4 ]
[ 1334531-20-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 5207 - 5224

73
[ 445-03-4 ]
[ 1334531-21-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 5207 - 5224

74
[ 445-03-4 ]
(3S)-1-(4-[(4-chloro-2-[(S)-hydroxy(2-methoxyphenyl)methyl]-6-methylphenyl)(2,2-dimethylpropyl)-amino]-4-oxobutanoyl)piperidine-3-carboxylic acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 5207 - 5224

75
[ 445-03-4 ]
[ 3282-30-2 ]
[ 1007652-06-3 ]

Yield	Reaction Conditions	Operation in experiment
37%	With dmap; triethylamine; In dichloromethane; at 0 - 20℃; for 16h;	General procedure: Triethylamine (6.70 ml, 48.2 mmol), pivaloyl chloride (2.92 g, 24.1 mmol) and 4-dimethylaminopyridine (0.267 g, 2.19 mmol) were added to an ice-cooled solution of 4-chloro-2-methoxyaniline hydrochloride (9a, 4.25 g, 21.9 mmol) in CH2Cl2 (100 ml). After being stirred for 16 h at room temperature, the solvent was concentrated, and the residue was dissolved in AcOEt and water. The organic material was extracted with AcOEt. The extract was washed with brine, dried over Na2SO4, and then concentrated in vacuo. The residue was purified by silica gel column chromatography (n-hexane/AcOEt = 8:2-3:1 as eluent) to give compound 10a (5.22 g, 21.6 mmol, 98percent) as a colorless powder.

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 5207 - 5224

76
C₂₀H₁₅ClO₃ [ No CAS ]
[ 445-03-4 ]
N-[4-chloro-2-(trifluoromethyl)phenyl]-2-(2-oxo-4-phenyl-2,6,7,8-tetrahydrocyclopenta[g]chromen-3-yl)acetamide [ No CAS ]