117324-58-0|Methyl 2-amino-5-(trifluoromethyl)benzoate| Ambeed

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Quality Control of [ 117324-58-0 ] Purity: 98% SDS Specification

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Product Details of [ 117324-58-0 ]

CAS No. :	117324-58-0
Formula :	C₉H₈F₃NO₂
M.W :	219.16
SMILES Code :	COC(C1=C(C=CC(=C1)C(F)(F)F)N)=O
MDL No. :	MFCD08234902
Boiling Point :	No data available
InChI Key :	QGFUDNJZHZNPCS-UHFFFAOYSA-N
Pubchem ID :	14233808

Safety of [ 117324-58-0 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 117324-58-0 ] Show Less

Physicochemical Properties

Num. heavy atoms	15
Num. arom. heavy atoms	6
Fraction Csp3	0.22
Num. rotatable bonds	3
Num. H-bond acceptors	5.0
Num. H-bond donors	1.0
Molar Refractivity	47.13
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	52.32 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.91
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	2.76
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	3.23
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	2.36
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	2.05
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.46

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.04
Solubility	0.202 mg/ml ; 0.000921 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-3.51
Solubility	0.0671 mg/ml ; 0.000306 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-3.01
Solubility	0.215 mg/ml ; 0.000979 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	Yes
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-5.68 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	1.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	1.62

Application In Synthesis of [ 117324-58-0 ]

* 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 [ 117324-58-0 ]

[ 117324-58-0 ] Synthesis Path-Downstream 1~35

1
[ 117324-58-0 ]
[ 358-23-6 ]
methyl 5-trifluoromethyl-2-[(trifluoromethyl)sulfonylamino]benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With triethylamine; In dichloromethane; at -78 - 20℃;	To a solution of <strong>[117324-58-0]methyl 2-amino-5-(trifluoromethyl)benzoate</strong> (0.25 g, 1.141 mmol) and triethylamine (0.115 g, 0.16 ml, 1.14 mmol) in 3 ml of dry dichloromethane was added trifluoromethane sulfonic anhydride (0.64 g, 2.28 mmol) at -78 C. The mixture was maintained below -40 C. for 3 h and stirred at RT for over night. Water was added and extracted with dichloromethane. The organic layer was dried and concentrated. The product was purified by flash chromatography to give 0.3 g (75%) of methyl 5-(trifluoromethyl)-2-(trifluoromethylsulfonamido)benzoate as white solid. MS found: (M+H)+=352.
75%	With triethylamine; In dichloromethane; at -78 - 20℃;	Preparation B6, Step 3: To a solution of <strong>[117324-58-0]methyl 2-amino-5-(trifluoromethyl)benzoate</strong> (0.25 g, 1.141 mmol) and triethylamine (0.115 g, 0.16 ml, 1.14 mmol) in 3 ml of dry dichloromethane was added trifluoromethane sulfonic anhydride (0.64 g, 2.28 mmol) at -78 C. The mixture was maintained below -40 C. for 3 h and stirred at RT for over night. Water was added and extracted with dichloromethane. The organic layer was dried and concentrated. The product was purified by flash chromatography to give 0.3 g (75%) of methyl 5-(trifluoromethyl)-2-(trifluoromethylsulfonamido)benzoate as white solid. MS found: (M+H)+=352.

References: [1]Patent: US2005/54627,2005,A1 .Location in patent: Page/Page column 38.
[2]Patent: US2005/54626,2005,A1 .Location in patent: Page/Page column 35.
[3]Bioscience, Biotechnology and Biochemistry,2004,vol. 68,p. 425 - 427.
[4]Journal of Fluorine Chemistry,2007,vol. 128,p. 1174 - 1181.

2
[ 67-56-1 ]
[ 117324-58-0 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of N-(4-(trifluoromethyl)phenyl)pivalamide (1 g, 4.08 mmol) in 20 ml of dry THF under nitrogen was added n-butyllithium (0.65 g, 4.1 ml) at 0 C. The reaction mixture was maintained at 0 C. for 3 h and added onto dry ice and stirred at RT over night. The reaction mixture was concentrated and the solid product obtained was dissolved in 25 ml of dry methanol and purged HCl gas for 30 min at 0 C. The mixture was stirred at RT for 2 h and heated at 55 C. over night. The reaction mixture was concentrated, basified with sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was washed with water, brine and concentrated. The crude product was purified by flash chromatography to give methyl 2-amino-5-(trifluoromethyl)benzoate (0.55 g) as white solid.

References: [1]Patent: US2005/54627,2005,A1 .Location in patent: Page/Page column 38.

3
[ 67-56-1 ]
[ 201230-82-2 ]
[ 57946-63-1 ]
[ 117324-58-0 ]

Yield	Reaction Conditions	Operation in experiment
88%	With triethylamine;1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; In dimethyl sulfoxide; at 80℃; under 5171.62 Torr; for 14 - 16h;	Example 139 Synthesis of 5- [Acetyl- (3, 5-bis-trifluoromethyl-benzyl)-amino]-7-trifluoromethyl-2, 3,4, 5- tetrahydro-benzo [b] azepine-1-carboxylic acid tert-butyl ester. Step 1. Preparation of Methyl-3-trifluoromethyl-2-aminobenzoate Add palladium (II) acetate (1.89 g, 8.4 mmol), 1,1- bis (diphenylphosphino) ferrocene (6.83 g, 12.3 mmol), and triethyl amine (32 mL, 44.0 mmol) to a solution of 2-bromo-4-trifluoromethylanaline (10.0 g, 42.0 mmol) in dimethylsulfoxide (283 mL) and methanol (187 mL). At 100 psi of carbon monoxide, heat the mixture to 80 C. After heating for 14-16 h cool the reaction to room temperature and filter. Dilute the organics with ethyl acetate (500 mL), wash with water (3x200 mL) and brine (200 mL). Dry the organics over sodium sulfate and filter. Remove solvent under vacuum and chromatograph the crude product using ethyl acetate/hexane (10 %) to elute. This provides the title compound (8.0 g, 88%) as an off white solid: H NMR (CDC13,400 MHz) 8 3.93 (s, 3H), 6.11 (bs, 2H), 6.73 (d, J = 8.4 Hz, 1H), 7.49 (dd, J = 2.0, 8.4 Hz, 1H), 8.17 (d, J = 2.0 Hz, 1H).

References: [1]Patent: WO2005/37796,2005,A1 .Location in patent: Page/Page column 138.

4
[ 117324-58-0 ]
[ 24424-99-5 ]
[ 209688-24-4 ]

Yield	Reaction Conditions	Operation in experiment
49%	With triethylamine; In dichloromethane; at 20℃; for 72h;	Step 2. Preparation of Methyl-3-trifluoromethyl-2-t-butoxycarbonylaminobenzoate. Add di-t-butyl dicarbonate (2.0 g, 9.1 mmol) to a solution of methyl-3- trifluoromethyl-2-aminobenzoate (2.0 g, 9.1 mmol) in dichloromethane (20 mL). To this mixture, add triethylamine (9.1 mmol) and stir at room temperature under an atmosphere of nitrogen for 72 h. Dilute the reaction with dichloromethane (100 mL) and wash with water (100 mL x 2). Dry the separated organic phase over sodium sulfate, filter, and remove solvent under vacuum. Chromatograph the product on silica gel using hexane/ethyl acetate (gradient, 2-10 % ethyl acetate/hexane) to elute. This provides the title compound as a colorless solid (1.43 g, 49%) : H NMR (CDCl3, 400 MHz) 8 1.54 (s, 9H), 3.99 (s, 3H), 7.75 (dd, J = 2.0, 9.2 Hz, 1H), 8.30 (d, J = 1.6 Hz, 1H), 8.64 (d, J = 9.2 Hz), 10.48 (s, 1H).

References: [1]Patent: WO2005/37796,2005,A1 .Location in patent: Page/Page column 138-139.

5
[ 209688-24-4 ]
[ 144-55-8 ]
[ 117324-58-0 ]

Yield	Reaction Conditions	Operation in experiment
	With trifluoroacetic acid; In dichloromethane;	REFERENCE EXAMPLE 28 Methyl 2-Amino-5-trifluoromethylbenzoate To a solution of methyl 2-t-butoxycarbonylamino-5-trifluoromethylbenzoate (3.80 g; prepared in Reference Example 27.) in methylene chloride (30 ml), trifluoroacetic acid (6 ml) was added. The mixture was stirred for 8 hours at room temperature. The solvent was distilled off azeotropically with toluene three times. To the reaction mixture, an aqueous sodium hydrogencarbonate solution was added to neutralize. The mixture was extracted with ethyl acetate, washed, dried, filtered and concentrated under the reduced pressure. The residue was purified on silica gel column chromatography (hexane:AcOEt 5:1) to give the title compound (2.35 g) having the following physical data. TLC: Rf 0.20 (hexane:AcOEt=5:1).

References: [1]Patent: US6448290,2002,B1 .

6
2-(N-pivaloyl)-5-trifluoromethylbenzoic acid [ No CAS ]
[ 117324-58-0 ]

Yield	Reaction Conditions	Operation in experiment
4.0 g (71%)	In methanol; chloroform;	PREPARATION 39 Methyl 2-Amino-5-trifluoromethylbenzoate A solution of 7.46 g (0.026 mol) of 2-(N-pivaloyl)-5-trifluoromethylbenzoic acid in 300 ml of methanol was cooled to 5 C. and saturated with gaseous hydrochloric acid. The reaction mixture was then heated at reflux for 20 hours, and evaporated to a solid. The crude solid was dissolved in chloroform and washed with saturated aqueous sodium bicarbonate. The organic layer was dried and evaporated to a viscous oil, which was purified by silica gel chromatography (9:1 hexane:ethylacetate). The title compound was isolated as a white solid, m.p. 51-52 C.; yield 4.0 g (71%).

References: [1]Patent: US4762838,1988,A .

7
[ 67-56-1 ]
[ 201230-82-2 ]
[ 163444-17-5 ]
[ 117324-58-0 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine;tetrakis(triphenylphosphine) palladium(0); In N,N-dimethyl-formamide; at 50℃; for 120h;	Step 1 Synthesis of [2-iodo-5-(trifluoromethyl)phenyl]methanol 2-Iodo-4-(trifluoromethyl)aniline (8.0 g, 27.9 mmol), methanol (5 ml) and triethylamine (10 ml) were dissolved in dimethylformamide (50 ml) and, under a carbon monoxide atmosphere, tetrakis(triphenylphosphine)palladium (1.6 g, 1.4 mmol) was added and the mixture was stirred at 50C for 5 days. The solvent was evaporated and work-up according to a conventional method gave a crude product of methyl 2-amino-5-(trifluoromethyl)benzoate.

References: [1]Patent: EP1736465,2006,A1 .Location in patent: Page/Page column 34.

8
[ 117324-58-0 ]
[ 4023-34-1 ]
[ 866831-56-3 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane; at 0 - 20℃;	Step 1 Synthesis of methyl {2-(cyclopropylcarbonyl)amino-5-trifluoromethyl}benzoate Methyl 2-amino-5-(trifluoromethyl)benzoate (0.20 g, 0.91 mmol) obtained as an intermediate for Step 1 of Example 7 was dissolved in methylene chloride (10 ml), triethylamine (0.25 ml, 1.82 mmol) and cyclopropanecarbonyl chloride (0.11 g, 1.1 mmol) were added at 0C, and the mixture was stirred overnight at room temperature. After work-up according to a conventional method, the mixture was purified by silica gel column chromatography (10% to 30% mixed solvent of ethyl acetate/hexane) to give the title compound (0.10 g, 0.35 mmol).

References: [1]Patent: EP1736465,2006,A1 .Location in patent: Page/Page column 35.

9
[ 117324-58-0 ]
[ 220107-65-3 ]

Yield	Reaction Conditions	Operation in experiment
		The obtained crude product was dissolved in tetrahydrofuran (20 ml), lithium aluminum hydride (1.0 g, 26.3 mmol) was added under cooling, and the mixture was stirred for 2 hr. Water (1 ml), 30% aqueous sodium hydroxide solution (1 ml) and water (3 ml) were sequentially added, the precipitate was filtered off, and the filtrate was concentrated to give a crude product of [2-amino-5-(trifluoromethyl)phenyl]methanol.

References: [1]Patent: EP1736465,2006,A1 .Location in patent: Page/Page column 34.

10
[ 117324-58-0 ]
[ 893761-44-9 ]
C₂₅H₂₁F₃N₂O₅S [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 5018 - 5022.

11
[ 67-56-1 ]
[ 124-38-9 ]
[ 25617-34-9 ]
[ 117324-58-0 ]

Yield	Reaction Conditions	Operation in experiment
		Preparation B6, Step 2: To a solution of N-(4-(trifluoromethyl)phenyl)pivalamide (1 g, 4.08 mmol) in 20 ml of dry THF under nitrogen was added n-butyllithium (0.65 g, 4.1 ml) at 0° C. The reaction mixture was maintained at 0° C. for 3 h and added onto dry ice and stirred at RT over night. The reaction mixture was concentrated and the solid product obtained was dissolved in 25 ml of dry methanol and purged HCl gas for 30 min at 0° C. The mixture was stirred at RT for 2 h and heated at 55° C. over night. The reaction mixture was concentrated, basified with sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was washed with water, brine and concentrated. The crude product was purified by flash chromatography to give methyl 2-amino-5-(trifluoromethyl)benzoate (0.55 g) as white solid.

References: [1]Patent: US2005/54626,2005,A1 .Location in patent: Page/Page column 34.

12
[ 117324-58-0 ]
3-(N,N-diethylsulfamoyl)benzoyl chloride [ No CAS ]
[ 1448009-48-0 ]

References: [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 6146 - 6155.

13
[ 117324-58-0 ]
[ 14002-51-8 ]
[ 1480483-19-9 ]

References: [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 8332 - 8338.

14
[ 117324-58-0 ]
[ 14002-51-8 ]
[ 1480482-49-2 ]

References: [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 8332 - 8338.

15
[ 67-56-1 ]
[ 83265-53-6 ]
[ 117324-58-0 ]

Yield	Reaction Conditions	Operation in experiment
94%	With sulfuric acid; for 18h;Reflux; Inert atmosphere;	Step 3 Methyl 2-amino-5-(trifluoromethyl)benzoate To a solution of 2-amino-5-(trifluoromethyl)benzoic acid (400 mg, 1.95 mmol) in MeOH (10 mL) at RT was added cone. H2SO4 (1 mL). The reaction was heated at reflux for 18 h, cooled to RT then diluted with EA (50 mL) and water (50 mL). The organic layer was washed with brine (50 mL), dried over Na2S04 and concentrated to give methyl 2-amino-5-(trifluoromethyl)benzoate (400 mg, 94.0% yield) as a yellow oil. Used without further purification.
51%	With sulfuric acid; at 125℃; for 2h;Microwave irradiation;	A solution of 2-amino-5-(trifluoromethyl)benzoic acid (1.07 g, 5.2 mmoles) in methanol (20 ml) was treated with concentrated sulphuric acid (0.5 ml) and heated under microwave conditions at 125 C. for 2 h. The mixture was evaporated to dryness and treated with water (100 ml) then basified to saturation with potassium carbonate and extracted with ethyl acetate (2*40 ml). The combined extracts were dried over sodium sulphate, filtered and evaporated to dryness. The residue was chromatographed on silica gel eluting with an ethyl acetate/isohexane gradient. This gave the title compound 1 as a colorless oil (0.59 g, 51%). 1H-NMR (CDCl3, 300 MHz) delta 8.15 (s, 1H, ArH), 7.47 (dd, J=2 and 9 Hz, 1H, ArH), 6.72 (d, J=9 Hz, 1H, ArH), 5.62-5.95 (brs, 2H, NH2), 3.92 (s, 3H, CH3).

References: [1]Patent: WO2016/23826,2016,A1 .Location in patent: Page/Page column 52; 53.
[2]Patent: US2015/210689,2015,A1 .Location in patent: Paragraph 0170; 0171; 0172.
[3]Journal of Medicinal Chemistry,2013,vol. 56,p. 8332 - 8338.

16
[ 887144-94-7 ]
[ 134-20-3 ]
[ 117324-58-0 ]
[ 64321-95-5 ]

References: [1]Organic Letters,2014,vol. 16,p. 1768 - 1771.

17
[ 117324-58-0 ]
methyl 2-amino-3-iodo-5-(trifluoromethyl)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With N-iodo-succinimide; trifluoroacetic acid; at 20℃; for 18h;	A solution of <strong>[117324-58-0]methyl 2-amino-5-(trifluoromethyl)benzoate</strong> (0.59 g, 2.7 mmoles) in trifluoroacetic acid (5 ml) was treated with N-iodosuccinimide (0.68 g, 3.0 mmoles) and stirred at ambient temperature for 18 h. The mixture was evaporated to dryness and the residue treated with water (25 ml) and basified with potassium carbonate then extracted with dichloromethane (25 ml). The organic phase was then washed with 10% sodium metabisulphite solution (25 ml), separated and dried over sodium sulphate, filtered and evaporated to dryness. The residue was chromatographed on silica gel eluting with an ethyl acetate/isohexane gradient. This gave the title compound 2 as a white solid (0.633 g, 68%). 1H-NMR (CDCl3, 300 MHz) delta 8.18 (d, J=3 Hz, 1H, ArH), 8.01 (d, J=3 Hz, 1H, ArH), 6.55-7.05 (brs, 2H, NH2), 3.92 (s, 3H, CH3).

References: [1]Patent: US2015/210689,2015,A1 .Location in patent: Paragraph 0173; 0174; 0175.

18
[ 117324-58-0 ]
methyl 5-(trifluoromethyl)-1H-indazole-7-carboxylate [ No CAS ]

References: [1]Patent: US2015/210689,2015,A1 .

19
[ 117324-58-0 ]
[ 32315-10-9 ]
[ 115306-75-7 ]
methyl 2-(3-(3-(tert-butyldimethylsilyloxy)propyl)ureido)-5-(trifluoromethyl)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78.3%		Step 4 Methyl 2-(3-(3-(tert-butyldimethylsilyloxy)propyl)ureido)-5-(trifluoromethyl)benzoate To a solution of <strong>[117324-58-0]methyl 2-amino-5-(trifluoromethyl)benzoate</strong> (400 mg, 1.70 mmol) and TEA (2.4 mL, 1.7 mmol) in DCM (5 mL) at 0C was added triphosgene (200 mg, 0.68 mmol) portionwise. The reaction was warmed to RT, stirred for 1 h then 3-(tert-butyldimethylsilyloxy)propan-l- amine (480 mg, 2.36 mmol) was added. The reaction mixture was stirred at RT for 1 h, poured into water-ice (30 mL) and extracted with EA (2x20 mL). The combined organic layers were washed with brine (20 mL), dried over Na2SC>4 and concentrated to give methyl 2-(3-(3-(tert- butyldimethylsilyloxy)propyl)ureido)-5-(trifluoromethyl)benzoate (600 mg, 78.3% yield) as a yellow oil. Used without further purification.

References: [1]Patent: WO2016/23826,2016,A1 .Location in patent: Page/Page column 52; 53; 54.

20
[ 454-92-2 ]
[ 117324-58-0 ]

References: [1]Patent: WO2016/23826,2016,A1 .

21
[ 1214373-54-2 ]
[ 117324-58-0 ]

References: [1]Patent: WO2016/23826,2016,A1 .

22
[ 117324-58-0 ]
3-(3-(tert-butyldimethylsilyloxy)propyl)-6-(trifluoromethyl)quinazoline-2,4(1H,3H)-dione [ No CAS ]

References: [1]Patent: WO2016/23826,2016,A1 .

23
[ 117324-58-0 ]
3-(3-(tert-butyldimethylsilyloxy)propyl)-1-methyl-6-(trifluoromethyl)quinazoline 2,4(1H,3H)-dione [ No CAS ]

References: [1]Patent: WO2016/23826,2016,A1 .

24
[ 117324-58-0 ]
3-(3-(tert-butyldimethylsilyloxy)propyl)-5-(hydroxy(phenyl)methyl)-1-methyl-6-(trifluoromethyl)quinazoline-2,4(1H,3H)-dione [ No CAS ]

References: [1]Patent: WO2016/23826,2016,A1 .

25
[ 117324-58-0 ]
[ 24424-99-5 ]
C₁₉H₂₄F₃NO₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81.2%	With dmap; In tetrahydrofuran; at 26 - 32℃; for 4h;Inert atmosphere;	To a solution of compound 13a (0.92 g, 4.2 mmol) and Boc 2O (3.17 g, 14.7 mmol) in THF (15 mL) was added DMAP (256 mg, 2.1 mmol) at 26-32C. The reaction was stirred at 26-32C for 4 h. The reaction solution was concentrated in vacuum to give the crude residue, which was purified by column chromatography on silica gel (0-10%EtOAc in petroleum ether) to afford the desired product compound 13b (1.43 g, 81.2% yield) as an off-white solid. LCMS: Rt = 1.078 min in 5-95AB_220&254. lcm chromatography (MERCK RP-18e 25-2mm), MS (ESI) m/z= 442.1 [M+23] +. 1H NMR (400MHz, CDCl 3) delta 8.28 (d, J=1.6 Hz, 1H), 7.95 (dd, J=2.0, 8.4 Hz, 1H), 7.53 (d, J=8.4 Hz, 1H), 3.93 (s, 3 H), 1.36 (s, 18 H).

References: [1]Patent: WO2019/149164,2019,A1 .Location in patent: Page/Page column 95; 60.

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[ 117324-58-0 ]
C₁₅H₂₀F₃NO₃ [ No CAS ]