[ CAS No. 129825-11-2 ]

Name: 129825-11-2|4-Chloro-3-(trifluoromethyl)acetophenone|98%
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Quality Control of [ 129825-11-2 ]

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Product Details of [ 129825-11-2 ]

CAS No. :	129825-11-2	MDL No. :	MFCD03094146
Formula :	C₉H₆ClF₃O	Boiling Point :	236.6°C at 760 mmHg
Linear Structure Formula :	-	InChI Key :	N/A
M.W :	222.59 g/mol	Pubchem ID :	-
Synonyms :

Calculated chemistry of of [ 129825-11-2 ]

Physicochemical Properties

Num. heavy atoms :	14
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.22
Num. rotatable bonds :	2
Num. H-bond acceptors :	4.0
Num. H-bond donors :	0.0
Molar Refractivity :	46.65
TPSA :	17.07 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) :	-4.93 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.05
Log Po/w (XLOGP3) :	3.84
Log Po/w (WLOGP) :	4.71
Log Po/w (MLOGP) :	3.37
Log Po/w (SILICOS-IT) :	3.84
Consensus Log Po/w :	3.56

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.82
Solubility :	0.0334 mg/ml ; 0.00015 mol/l
Class :	Soluble
Log S (Ali) :	-3.89
Solubility :	0.0284 mg/ml ; 0.000128 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.24
Solubility :	0.0127 mg/ml ; 0.0000571 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	1.53

Safety of [ 129825-11-2 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P264-P280-P302+P352+P332+P313+P362+P364-P305+P351+P338+P337+P313	UN#:	N/A
Hazard Statements:	H315-H319	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 129825-11-2 ]

* 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.

Downstream synthetic route of [ 129825-11-2 ]

[ 129825-11-2 ] Synthesis Path-Downstream 1~30

1
1-Chloro-4-((E)-2-ethoxy-vinyl)-2-trifluoromethyl-benzene [ No CAS ]
[ 129825-11-2 ]

Yield	Reaction Conditions	Operation in experiment
5.16 g	With hydrogenchloride In tetrahydrofuran for 3h;

Reference： [1]Gross, Raymond S.; Guo, Zhiqiang; Dyck, Brian; Coon, Tim; Huang, Charles Q.; Lowe, Richard F.; Marinkovic, Dragan; Moorjani, Manisha; Nelson, Jodene; Zamani-Kord, Said; Grigoriadis, Dimitri E.; Hoare, Sam R. J.; Crowe, Paul D.; Bu, Jane Han; Haddach, Mustapha; McCarthy, James; Saunders, John; Sullivan, Robert; Chen, TaKung; Williams, John P. [Journal of Medicinal Chemistry, 2005, vol. 48, # 18, p. 5780 - 5793]

2
[ 129825-11-2 ]
[ 73183-34-3 ]
[ 866141-77-7 ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In toluene for 48h; Heating;

3
[ 129825-11-2 ]
6-cyclopropylmethyl-7-ethyl-2-(4-isopropyl-2-trifluoromethyl-phenyl)-4-methyl-7,8-dihydro-6<i>H</i>-1,3,6,8a-tetraaza-acenaphthylene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: PdCl₂(dppf); KOAc / toluene / 48 h / Heating 2: 3.78 g / aq. sodium carbonate; barium hydroxide; Pd(PPh₃)4 / toluene; ethanol / 100 °C 3: tetrahydrofuran; toluene / 2.5 h / 20 - 60 °C 4: 45 percent / MgSO₄; p-toluenesulfonic acid; trifluoroacetic acid / toluene / 16 h / Heating 5: H₂ / PtO / ethanol / 1 h / 2068.59 Torr

4
[ 129825-11-2 ]
[ 866141-78-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: PdCl₂(dppf); KOAc / toluene / 48 h / Heating 2: 3.78 g / aq. sodium carbonate; barium hydroxide; Pd(PPh₃)4 / toluene; ethanol / 100 °C

5
[ 129825-11-2 ]
[ 866141-79-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: PdCl₂(dppf); KOAc / toluene / 48 h / Heating 2: 3.78 g / aq. sodium carbonate; barium hydroxide; Pd(PPh₃)4 / toluene; ethanol / 100 °C 3: tetrahydrofuran; toluene / 2.5 h / 20 - 60 °C 4: 45 percent / MgSO₄; p-toluenesulfonic acid; trifluoroacetic acid / toluene / 16 h / Heating

6
[ 129825-11-2 ]
2-[4-(6-cyclopropylmethyl-7-ethyl-4-methyl-7,8-dihydro-6<i>H</i>-1,3,6,8a-tetraaza-acenaphthylen-2-yl)-3-trifluoromethyl-phenyl]-propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: PdCl₂(dppf); KOAc / toluene / 48 h / Heating 2: 3.78 g / aq. sodium carbonate; barium hydroxide; Pd(PPh₃)4 / toluene; ethanol / 100 °C 3: tetrahydrofuran; toluene / 2.5 h / 20 - 60 °C

7
[ 348-84-5 ]
[ 129825-11-2 ]

Yield	Reaction Conditions	Operation in experiment
95%	With oxalyl dichloride; triethylamine; In dichloromethane; dimethyl sulfoxide; at -78℃;	[4-CHLORO-3- (TRIFLUOROMETHYL)] benzylaldhyde (3.0 g, 14.4 mmol) in diethyl ether was cooled [TO-78 C. METHYLMAGNESIUM] chloride (3. 0M solution in THF, 29 mmol) was added dropwise. The reaction was warmed up slowly [TO-20] C. TLC showed the reaction was complete. It was quenched with saturated amonium chloride solution. The aqueous layer was extracted with ethyl acetate, organic layer wre combined and washed with water, brine, and dried with magnesium sulfate. This gave [1- (4-CHLORO-3-TRIFLUOROMETHYLPHENYL)] ethanol (3.2g, [99%)] after the solvent was removed under reduced pressure. [1- (4-CHLORO-4-TRIFLUOROMETHYL-] phenyl) ethanol was then oxidized by [SWERN] oxidation (2.5 eq. DMSO, 1.2 eq. oxyal chloride, 5 eq. triethylamine, [60ML] of [DICHLOROMETHANE,-78] C). The resulting 1- (3-chloro-4- trifluoromethylphenyl) ethanone (3 g, 95% yield) was brominated according to a literature [PROCEDURE (HORNG-CHIH, HUANG ET AL. , J. MED. CHEM. ; 1996, VOL. 39,253-266). 4-CHLORO-3- (TRIFLUOROMETHYL) -PHENACYL BROMIDE WAS OBTAINED IN 70% YIELD. LC/MS (ES+) M/E 303 [M+1]]
87%	With pyridinium chlorochromate; In dichloromethane; at 20℃;	The compound 149A (2.62 g, 11.7 mmol) is dissolved in53 mL of DCM in the presence of 3.8 g of celite. PCC(3.77 g, 17.5 mmol) is added at room temperature and the reaction medium is stirred overnight before being filtered. The filtrate is concentrated under reduced pressure. The thereby obtained residue is purified on a column of 80 g of silica (32 mL / min, gradient of 0% to 30% EtOAc in heptane in 26 minutes), in order to obtain the compound 149B (2.27 g, 87%) .HPLC: RT = 5.84 min, 97% (colonne XBridge)1H NMR, dmso-de, delta (ppm) : 2.65 (s, 3H); 7.92 (d, IH); 8.22-8.27 (m, 2H) .

Reference： [1]Patent: WO2003/101970,2003,A1 .Location in patent: Page 10-11
[2]Patent: WO2010/100139,2010,A1 .Location in patent: Page/Page column 102-103

8
[ 129825-11-2 ]
[ 125486-96-6 ]
[ 1045771-63-8 ]

Yield	Reaction Conditions	Operation in experiment
84%	With caesium carbonate In 1,4-dioxane at 120℃; for 15h;

Reference： [1]Anjanappa, Prakash; Mullick, Dibakar; Selvakumar, Kumaravel; Sivakumar, Manickam [Tetrahedron Letters, 2008, vol. 49, # 31, p. 4585 - 4587]

9
[ 129825-11-2 ]
[ 1100768-05-5 ]

Yield	Reaction Conditions	Operation in experiment
69%	With sodium hydrogensulfide In 1-methyl-pyrrolidin-2-one at 140 - 160℃; for 3h;	74.1 Sodium hydrogen sulfide hydrate (NaSHxH2O) (15.81 g, 213.4 mmol) ) was dehydrated in N-methylpyrrolidone (150 ml) at 160 0C under argon. 4-Chloro-3- trifluoromethyl)acetophenone (19.00 g, 85.36 mmol) was added to the mixture at 140 0C and stirring was continued for 3 h at 160 0C. The solvent was removed under reduced pressure and water (100 ml) and hydrochloric acid (6 N) were added to the crude product. The precipitate was filtered, washed and purified by silica gel chromatography using ethyl acetate/n-heptane to yield 13.00 g (yield: 69%) of the. desired product.

Reference： [1]Current Patent Assignee: SANOFI - WO2009/7015, 2009, A1 Location in patent: Page/Page column 61

10
[ 129825-11-2 ]
[ 1937-19-5 ]
[ 1192599-27-1 ]

Yield	Reaction Conditions	Operation in experiment
75%	In ethanol at 90℃; for 18h;

Reference： [1]Gaubert, Gilles; Bertozzi, Fabio; Kelly, Nicholas M.; Pawlas, Jan; Scully, Audra L.; Nash, Norman R.; Gardell, Luis R.; Lameh, Jelveh; Olsson, Roger [Journal of Medicinal Chemistry, 2009, vol. 52, # 21, p. 6511 - 6514]

11
[ 129825-11-2 ]
[ 3124-37-6 ]
[ 1257310-75-0 ]

Yield	Reaction Conditions	Operation in experiment
91%	With palladium diacetate; caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 120℃; for 15h; Inert atmosphere;

Reference： [1]Mullick, Dibakar; Anjanappa, Prakash; Selvakumar, Kumaravel; Ruckmani, Kandasamy; Sivakumar, Manickam [Tetrahedron Letters, 2010, vol. 51, # 46, p. 5984 - 5987]

12
[ 129825-11-2 ]
C₂₅H₂₆ClF₃N₄O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: hydrogenchloride / ethanol; water / Reflux 2: methanol; sodium tetrahydroborate / 0 °C 3: tetrahydrofuran / 20 °C

Reference： [1]Chae, Eunhee; Yi, Hanju; Choi, Yeonjung; Cho, Hyeon; Lee, Kiho; Moon, Hongsik [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 7, p. 2434 - 2439]

13
[ 129825-11-2 ]
[ 1083076-04-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: hydrogenchloride / ethanol; water / Reflux 2: methanol; sodium tetrahydroborate / 0 °C 3: tetrahydrofuran / 20 °C 4: ammonium hydroxide

Reference： [1]Chae, Eunhee; Yi, Hanju; Choi, Yeonjung; Cho, Hyeon; Lee, Kiho; Moon, Hongsik [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 7, p. 2434 - 2439]

14
[ 129825-11-2 ]
[ 1369891-72-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: hydrogenchloride / ethanol; water / Reflux 2: methanol; sodium tetrahydroborate / 0 °C

Reference： [1]Chae, Eunhee; Yi, Hanju; Choi, Yeonjung; Cho, Hyeon; Lee, Kiho; Moon, Hongsik [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 7, p. 2434 - 2439]

15
[ 129825-11-2 ]
C₁₃H₉ClF₃NO₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: trichlorophosphate / 0.25 h / 25 °C 1.2: 0.5 h / 20 - 60 °C 1.3: 0.5 h 2.1: natrium; methanol / 0.5 h / Reflux
	Multi-step reaction with 2 steps 1.1: trichlorophosphate / 25 °C 1.3: 0.5 h 2.1: sodium methoxide / methanol / 0.5 h / Reflux

Reference： [1]Sahner, J. Henning; Groh, Matthias; Negri, Matthias; Haupenthal, Jörg; Hartmann, Rolf W. [European Journal of Medicinal Chemistry, 2013, vol. 65, p. 223 - 231]
[2]Kiefer, Alexander F.; Bousis, Spyridon; Hamed, Mostafa M.; Diamanti, Eleonora; Haupenthal, Jörg; Hirsch, Anna K.H. [Journal of Medicinal Chemistry, 2021]

16
[ 129825-11-2 ]
C₁₂H₇ClF₃NO₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: trichlorophosphate / 0.25 h / 25 °C 1.2: 0.5 h / 20 - 60 °C 1.3: 0.5 h 2.1: natrium; methanol / 0.5 h / Reflux 3.1: potassium hydroxide / methanol; lithium hydroxide monohydrate / 3 h / Reflux
	Multi-step reaction with 3 steps 1.1: trichlorophosphate / 25 °C 1.3: 0.5 h 2.1: sodium methoxide / methanol / 0.5 h / Reflux 3.1: potassium hydroxide / methanol; lithium hydroxide monohydrate / 3 h / Reflux

17
[ 129825-11-2 ]
C₁₃H₅ClF₃NO₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: trichlorophosphate / 0.25 h / 25 °C 1.2: 0.5 h / 20 - 60 °C 1.3: 0.5 h 2.1: natrium; methanol / 0.5 h / Reflux 3.1: potassium hydroxide / methanol; lithium hydroxide monohydrate / 3 h / Reflux 4.1: tetrahydrofuran; toluene / 2 h / 20 °C
	Multi-step reaction with 4 steps 1.1: trichlorophosphate / 25 °C 1.3: 0.5 h 2.1: sodium methoxide / methanol / 0.5 h / Reflux 3.1: potassium hydroxide / methanol; lithium hydroxide monohydrate / 3 h / Reflux 4.1: tetrahydrofuran; toluene / 2.5 h

18
[ 129825-11-2 ]
5-(3’-trifluoromethyl,4’-Chlorophenyl)-3-[(N-ethylbenzylamino)carbonylamino]thiophen-2-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: trichlorophosphate / 0.25 h / 25 °C 1.2: 0.5 h / 20 - 60 °C 1.3: 0.5 h 2.1: sodium; methanol / 0.5 h / Reflux 3.1: potassium hydroxide / methanol; water / 3 h / Reflux 4.1: tetrahydrofuran; toluene / 2 h / 20 °C 5.1: water / 100 °C

Reference： [1]Sahner, J. Henning; Groh, Matthias; Negri, Matthias; Haupenthal, Jörg; Hartmann, Rolf W. [European Journal of Medicinal Chemistry, 2013, vol. 65, p. 223 - 231]

19
[ 129825-11-2 ]
[ 33513-42-7 ]
C₁₀H₄Cl₂F₃N [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 25℃; for 0.25h; Stage #2: 1-[4-chloro-3-(trifluoromethyl)phenyl]ethanone at 20 - 60℃; for 0.5h; Stage #3: With hydroxyamino hydrochloride for 0.5h;	6.1.2.1. General procedure for the synthesis of 5-aryl-3-amino-2-carboxylic acid methyl ester (II). General procedure: POCl3 (26.1 g, 0.17 mol) was added dropwise to DMF (24.9 g, 0.34 mol) maintaining the temperature beyond 25 °C (cooling in ice bath) and stirred for additional 15 min. The acetophenone I (85.0 mmol) was added slowly and the temperature was kept between 40 and 60 °C. After complete addition, the mixture was stirred for 30 min at room temperature. Hydroxylamine hydrochloride (23.6 g,0.34 mol) was carefully added portionwise (exothermic reaction) and the reaction was stirred for additional 30 min without heating. After cooling to room temperature, the mixture was poured into ice water (300 mL). The precipitated b-chloro-cinnamonitrile was collected by filtration, washed with H2O(2 50 mL) and dried under reduced pressure over CaCl2. In the next step sodium (1.93 g, 84.0 mmol) was dissolved in MeOH(85 mL) and methylthioglycolate (6.97 g, 65.6 mmol) was added to the stirred solution. The b-chloro-cinnamonitrile (61.1 mmol) was added and the mixture was heated to reflux for 30 min. After cooling to room temperature, the mixture was poured into icewater (300 mL). The precipitated solid was collected by filtration, washed with H2O (2 50 mL) and dried under reduced pressure over CaCl2. If necessary, recrystallisation from EtOH was performed.
	Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 25℃; Stage #2: 1-[4-chloro-3-(trifluoromethyl)phenyl]ethanone Stage #3: With hydroxyamino hydrochloride for 0.5h;

20
[ 129825-11-2 ]
[ 411235-57-9 ]
1-[4-cyclopropyl-3-(trifluoromethyl)phenyl]ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; palladium diacetate; tricyclohexylphosphine In water; toluene for 5h; Reflux;	124 Reference Production Example 124 Reference Production Example 124 A mixture of 0.45 g of 1-(4-chloro-3-trifluoromethylphenyl)ethanone, 0.22 g of cyclopropylboronic acid, 0.02 g of palladium acetate, 0.06 g of tricyclohexylphosphine, 1. 49 g of potassium phosphate, 10 mL of toluene, and 0.5 mL of water was reacted by heating under reflux for 5 hours and the thus obtained crude product was subjected to silica gel column chromatography to obtain 4'-cyclopropyl-3'-trifluoromethylacetophenone (C124A). 1H-NMR (CDCl3) δ (ppm): 8.19 (1H, s), 8.01 (1H, d, J = 7.8 Hz), 7.07 (1H, d, J = 8.2 Hz), 2.61 (3H, s), 2.31-2.24 (1H, m), 1.18-1.13 (2H, m), 0.88-0.86 (2H, m).
1 g	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate In water; toluene at 100℃; for 3h; Inert atmosphere;	38 Preparation Example 38 Preparation Example 38 A mixture of 1-[4-chloro-3-(trifluoromethyl)phenyl]ethanone (1.0 g), cyclopropylboronic acid (780 mg), dicyclohexyl (2',6'-dimethoxybiphenyl-2-yl)phosphine (185 mg), tripotassium phosphate (3.0 g), palladium acetate (II) (51 mg), toluene (10 mL), and water (1 mL) was stirred at 100°C for 3 hours under an argon atmosphere. The reaction mixture was cooled to room temperature, ethyl acetate and water were added thereto, and the insoluble materials were separated by filtration. The filtrate was extracted with ethyl acetate and the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain 1-[4-cyclopropyl-3-(trifluoromethyl)phenyl]ethanone (1.0 g) as an oil.
1 g	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate In water; toluene at 100℃; for 3h; Inert atmosphere;	33 Preparation Example 33 A mixture of 1-[4-chloro-3-(trifluoromethyl)phenyl]ethanone (1.0 g), cyclopropylboronic acid (780 mg), dicyclohexyl(2’,6’-dimethoxybiphenyl-2-yl)phosphine (185 mg), tripotassium phosphate (3.0 g), palladium acetate (II) (51mg), toluene (10 mL), and water (1.0 mL) was stirred at 100°C for 3 hours under an argon atmosphere, and then cooledto room temperature. Ethyl acetate and water were added to the reaction mixture, insoluble materials were removed byfiltration, and then the filtrate was extracted with ethyl acetate. The organic layer was washed with saturated brine, driedover anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified withsilica gel column chromatography (hexane-ethyl acetate) to obtain 1-[4-cyclopropyl-3-(trifluoromethyl)phenyl]ethanone(1.0 g) as an oil.

Reference： [1]Current Patent Assignee: Sumitomo Chemical (w/o Dongwoo Fine-Chem); SUMITOMO CHEMICAL COMPANY LIMITED - EP2927218, 2015, A1 Location in patent: Paragraph 0866
[2]Current Patent Assignee: ASTELLAS PHARMA INC. - EP3153511, 2017, A1 Location in patent: Paragraph 0178
[3]Current Patent Assignee: ASTELLAS PHARMA INC. - EP3196200, 2017, A1 Location in patent: Paragraph 0165

21
[ 129825-11-2 ]
[ 98-80-6 ]
1-(4-phenyl-3-trifluoromethylphenyl)ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium fluoride; palladium diacetate; XPhos In tetrahydrofuran for 15h; Reflux;	136 Reference Production Example 136 Reference Production Example 136 (0875) A mixture of 0.45 g of 1-(4-chloro-3-trifluoromethylphenyl)ethanone, 0.22 g of phenylboronic acid, 0.02 g of palladium acetate, 2-(dichlorohexylphosphino)-2',4', 0.03 g of 6'-triisopropyl-1,1'-biphenyl, 0.52 g of potassium fluoride, and 5 mL of tetrahydrofuran was reacted while heating under reflux for 15 hours. The obtained crude product was subjected to silica gel column chromatography to obtain 1-(4-phenyl-3-trifluoromethylphenyl)ethanone (C136A). 1H-NMR (CDCl3) δ (ppm) : 8.34 (1H, s), 8.13 (1H, d, J = 7.9 Hz), 7.47-7.41 (4H, m), 7.33-7.31 (2H, m), 2.67 (3H, s).

Reference： [1]Current Patent Assignee: Sumitomo Chemical (w/o Dongwoo Fine-Chem); SUMITOMO CHEMICAL COMPANY LIMITED - EP2927218, 2015, A1 Location in patent: Paragraph 0875

22
[ 129825-11-2 ]
[ 17356-08-0 ]
[ 240136-66-7 ]

Yield	Reaction Conditions	Operation in experiment
93%	Stage #1: 1-(4-chloro-3-(trifluoromethyl)phenyl)ethanone With phenyltrimethylammonium tribromide In tetrahydrofuran at 20℃; for 0.5h; Stage #2: thiourea In ethanol at 80℃; for 3h;	6.3.13. 4-[4-Methoxy-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-amine (38) General procedure: 1-[4-Methoxy-3-(trifluoromethyl)phenyl]ethanone (35, 15 g) andtetrahydrofuran (270 mL) were mixed, and phenyltrimethylammoniumtribromide (28.42 g) was added thereto, followed by stirring at roomtemperature for 30 min. The precipitated insoluble materials were separatedby filtration and the filtrate was concentrated under reducedpressure.The obtained residue and ethanol (260 mL) were mixed, andthiourea (6.81 g) was added thereto, followed by stirring at 80 °C for3 h. The reaction mixture was cooled to room temperature, and water, a1 M aqueous sodium hydroxide solution, and ethyl acetate were added.The organic layer was washed with a 1 M aqueous sodium hydroxidesolution, water, and a saturated aqueous sodium chloride solution, anddried over anhydrous magnesium sulfate. The insoluble materials wereseparated by filtration and the filtrate was concentrated under reducedpressure. The residue was purified by silica gel column chromatography(hexane-ethyl acetate) to obtain 38 (16.18 g, 86%) as a white solid:
24 g	Stage #1: 1-(4-chloro-3-(trifluoromethyl)phenyl)ethanone With phenyltrimethylammonium tribromide In tetrahydrofuran at 20℃; for 2h; Stage #2: thiourea In ethanol at 80℃; for 5h;	213 Preparation Example 213 Phenyltrimethylammonium tribromide (44 g) was added to a mixture of 1-[4-chloro-3-(trifluoromethyl)phenyl]ethanone(25 g) and tetrahydrofuran (300 mL), and the reaction mixture was stirred at room temperature for 2 hours. Theinsoluble materials were separated by filtration, and the filtrate was concentrated under reduced pressure. The obtainedcompound and ethanol (300 mL) were mixed, and thiourea (10 g) was added to the mixture, and then was stirred at80°C for 5 hours. The reaction mixture was cooled to room temperature, and the precipitated solid was collected byfiltration. The filtrate was concentrated under reduced pressure, and the precipitated solid was washed with ethyl acetate,and was collected by filtration. This solid was combined with the solid which was previously collected by filtration, and the combined solid was dispersed into ethyl acetate and a saturated aqueous sodium hydrogen carbonate solution soas to extract with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydroussodium sulfate, and then concentrated under reduced pressure. The obtained solid was washed with hexane, collectedby filtration, and dried to obtain 4-[4-chloro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-amine (24 g) as a solid.

Reference： [1]Inagaki, Yusuke; Ino, Katsutoshi; Ishizu, Kenichiro; Koike, Takanori; Maeda, Jun; Negoro, Kenji; Shimoshige, Yukinori; Takahashi, Taisuke; Tanaka, Hiroaki; Tsukamoto, Issei; Yokoyama, Kazuhiro [Bioorganic and medicinal chemistry, 2020]
[2]Current Patent Assignee: ASTELLAS PHARMA INC. - EP3196200, 2017, A1 Location in patent: Paragraph 0176

23
[ 129825-11-2 ]
N-{4-[4-chloro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl}acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: phenyltrimethylammonium tribromide / tetrahydrofuran / 2 h / 20 °C 1.2: 5 h / 80 °C 2.1: pyridine / 4 h / 60 °C