[ CAS No. 161622-05-5 ] {[proInfo.proName]}

Name: 161622-05-5|3-Fluoro-5-trifluoromethylbenzoic acid|98%
Brand: Ambeed
SKU: A139085
Price: 9.0 USD
Availability: InStock
Rating: 95 (25 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

DV 2D 3D

3d Animation Molecule Structure of 161622-05-5

Structure of 161622-05-5 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 161622-05-5 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 161622-05-5 ]

SDS Specification

Alternatived Products of [ 161622-05-5 ]

Product Details of [ 161622-05-5 ]

CAS No. :	161622-05-5	MDL No. :	MFCD00061293
Formula :	C₈H₄F₄O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	NSGKIIGVPBTOBF-UHFFFAOYSA-N
M.W :	208.11	Pubchem ID :	519222
Synonyms :

Calculated chemistry of [ 161622-05-5 ]

Physicochemical Properties

Num. heavy atoms :	14
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.12
Num. rotatable bonds :	2
Num. H-bond acceptors :	6.0
Num. H-bond donors :	1.0
Molar Refractivity :	38.36
TPSA :	37.3 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.84 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.47
Log Po/w (XLOGP3) :	2.43
Log Po/w (WLOGP) :	4.12
Log Po/w (MLOGP) :	3.09
Log Po/w (SILICOS-IT) :	2.69
Consensus Log Po/w :	2.76

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.85

Water Solubility

Log S (ESOL) :	-2.85
Solubility :	0.296 mg/ml ; 0.00142 mol/l
Class :	Soluble
Log S (Ali) :	-2.86
Solubility :	0.29 mg/ml ; 0.00139 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.94
Solubility :	0.237 mg/ml ; 0.00114 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.59

Safety of [ 161622-05-5 ]

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

Application In Synthesis of [ 161622-05-5 ]

* 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 [ 161622-05-5 ]
Downstream synthetic route of [ 161622-05-5 ]

[ 161622-05-5 ] Synthesis Path-Upstream 1~1

1
[ 161622-05-5 ]
[ 328-69-8 ]

Reference： [1] Patent: WO2015/130957, 2015, A1,

[ 161622-05-5 ] Synthesis Path-Downstream 1~81

1
[ 6638-79-5 ]
[ 161622-05-5 ]
[ 329941-91-5 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1175 - 1182

2
[ 620611-27-0 ]
[ 161622-05-5 ]
[ 918431-91-1 ]

Yield	Reaction Conditions	Operation in experiment
		te?'/-butyl 4-fluoro-4-rf3-fluoro-5-('trifluoromethyl')benzamido')methyl)piperidine-l-carboxylate (3-5'); 1-Hydrozybenzotriazole (0.973 g, 7.2 mmol) and 3-fluoro-5-(trifluoromethyl)benzoic acid (1.25 g, 6.0 mmol) were suspended in 30 mL diy CH2Cl2. Diisopropylethylamine (2.1 mL, 12.0 mmol) was added and all compounds went into solution. Amine 3-4 (1.39 g, 6.0 mmol) was added in 30 mL dry CH2Cl2. PS-carbodiimide resin (7.5 g, 12.0 mmol) was then added and the mixture was vigorously stirred overnight. MP-carbonate resin (4.Og, 12.0 mmol) was added and stirring was resumed for 3 h. The reaction was then filtered to remove resin and concentrated in vacuo. A 40 g SiO2 column was run in 0-50% EtOAc/hexanes, yielding 902 mg of 3-5 (36% over 3 steps) as a viscous yellow oil. 1H NMR (CDCl3, 300 MHz): 7.84 (s, IH), 7.73 (d, J= 8.4 Hz, IH), 7.45 (d, J= 8.4 Hz, IH), 3.92 (br, 2H), 3.65 (m, 2H), 3.10 (m, 2H), 1.68 (m, 4H), 1.43 (s, 9H); MS (Electrospray): m/z 445.2 (M+Na), 367.1 (M- t-Bu+H).

Reference： [1]Patent: WO2007/2884,2007,A2 .Location in patent: Page/Page column 24

3
[ 161622-05-5 ]
[ 329941-93-7 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1175 - 1182

4
[ 161622-05-5 ]
[ 329941-92-6 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1175 - 1182

5
[ 161622-05-5 ]
[ 675139-67-0 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1175 - 1182

6
[ 161622-05-5 ]
[ 329946-87-4 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1175 - 1182

7
[ 161622-05-5 ]
[ 675139-66-9 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1175 - 1182

8
[ 161622-05-5 ]
GW₄₅₁₁ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1175 - 1182

9
[ 161622-05-5 ]
2-[4-chloro-2-(3-fluoro-5-trifluoromethyl-benzoyl)-phenoxy]-<i>N</i>-[2-methyl-4-(3-sulfamoyl-propoxy)-phenyl]-acetamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 1175 - 1182

10
[ 641615-38-5 ]
[ 161622-05-5 ]
[ 812700-17-7 ]

Yield	Reaction Conditions	Operation in experiment
	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In DMF (N,N-dimethyl-formamide); at 20℃;	A mixture of 4-Methyl-N3- (4-pyrazin-2-yl-pyrimidin-2-yl)-benzene-1, 3-diamine (0.55 g, 1.98 MMOL), 3-Fluoro-5-trifluoromethyl-benzoic acid (0.43 g, 2.08 MMOL), BOP (1.05 g, 2.38 MMOL) and DIEA (1.25 mL, 7.20 MMOL) is stirred in 9.0 mL of DMF at room temperature overnight. 25 mL of water is added to the precipitate. The resulting suspension is allowed to stir at room temperature for one hour. It is then filtered through a Buchner funnel, air dried and triturated with 10.0 mL of CH30H for 1 hour and dried. 0.80 g of 3-FLUORO-N- [4-METHYL-3- (4-PYRAZIN-2- yl-pyrimidin-2-ylamino)-phenyl]-5-trifluoromethyl-benzamide is obtained as a pale yellow solid. RH NMR (DMSO, 500MHZ) : No. (ppm) 10.49 (s, 1H), 9.49 (s, 1H), 9.10 (s, 1H), 8.79 (s, 2H), 8. 62 (d, 2H, J=4.81 Hz), 8.10-8. 20 (m, 3H), 7.96 (d, 1H, J=8.66Hz), 7. 63 (d, 1H, J=4. 78Hz), 7.48 (dd, 1H, J1=8. 46Hz, J2=2. 05 HZ), 7.26 (d, 1H, J=8.09Hz), 2.26 (s, 3H). API-MS m/z 469.1 ([M+H] +, CALCD 469.1)

Reference： [1]Patent: WO2004/110452,2004,A1 .Location in patent: Page/Page column 51-52

11
[ 161622-05-5 ]
5-fluoro-3-trifluoromethylbenzoylguanidine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 34 5-Fluoro-3-trifluoromethylbenzoylguanidine hydrochloride Colorless crystals, m.p. 150-51 C. from 5-fluoro-3-trifluoromethylbenzoic acid following the general protocol

Reference： [1]Patent: US5866610,1999,A

12
[ 100-51-6 ]
[ 161622-05-5 ]
[ 53985-39-0 ]

Yield	Reaction Conditions	Operation in experiment
58%		1 g (4.8 mmol) of <strong>[161622-05-5]3-trifluoromethyl-5-fluorobenzoic acid</strong> was dissolved in 10 mL of dimethylformamide, then 623 mg (5.76 mmol) of benzyl alcohol was added thereto dropwise. 423 mg (60%, 10.5 mmol) of sodium hydride was slowly added to the reaction solution at 0C, and stirred for 10 minutes, then the solution was heated at 50 C for 4 hours. The reaction solution was diluted with ethyl acetate and washed with water, and then dried over anhydrous magnesium sulfate. Solvent was removed and the residue was purified by column chromatography to obtain 825 mg of the title compound in a yield of 58%.NMR: 1H-NMR(CDCl3) delta 7.95(1H, s), 7.85(1H, s), 7.50~7.30(6H, m), 5.13(2H, s)Mass(EI) 297 (M++l)

Reference： [1]Patent: WO2007/58504,2007,A1 .Location in patent: Page/Page column 78

13
[ 942631-61-0 ]
[ 161622-05-5 ]
5-[3-fluoro-5-(trifluoromethyl)benzoyl]amino}-2-methyl-N-(2-methyl-1,3-thiazol-5-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With pyridine; HATU; In N,N-dimethyl-formamide; for 16h;	Example 25; 5-[3-Fluoro-5-Ctrifluoromethyl)benzoyl1amino}-2-methyl-N-(2-methyl-l,3-thiazol-5- vDbenzamide; To a solution of 5-amino-2-methyl-N-(2-methyl-l,3-thiazol-5-yl)benzamide (Method25, 100 mg, 0.40 mmol) and <strong>[161622-05-5]3-fluoro-5-(trifluoromethyl)benzoic acid</strong> (85 mg, 0.40 mmol) in anhydrous DMF (5 ml) was added HATU (154 mg, 0.40 mmol) and pyridine (5 eq.). After stirring for 16 hours, the reaction mixture was diluted with EtOAc, washed with water, dried (Na2SO4) and concentrated. Purification by column chromatography (Hex:EtOAc) gave 10 121mg (68%) of a white solid.1H NMR Acetone-d6 10.70 (s, 1 H) 9.94 (s, 1 H) 8.19 (s, 1 H) 8.08 (s, 1 H) 8.04 (d, 1 H) 7.80 (dd, 2 H) 7.49 (s, 1 H) 7.32 (d, 1 H) 2.60 (s, 3 H) 2.43 (s, 3 H); m/z: 438.

Reference： [1]Patent: WO2007/71955,2007,A1 .Location in patent: Page/Page column 62

14
[ 328-74-5 ]
[ 161622-05-5 ]
[ 691887-56-6 ]

Yield	Reaction Conditions	Operation in experiment
		Example 64 (General Procedure (D)) N-(3,5-Bis-Trifluoromethyl-Phenyl)-3-Fluoro-5-Trifluoromethyl-Benzamide. The title compound was prepared from <strong>[161622-05-5]3-fluoro-5-trifluoromethyl-benzoic acid</strong> and 3,5-Bis-trifluoromethylanilin. 1H NMR (DMSO-d6): delta ppm 7.88 (m, 1 H) 8.04 (d, 1 H) 8.15 (d, 1 H) 8.22 (m, 1 H) 8.48 (m, 2 H) 11.04 (s, 1 H); HPLC-MS (Method A): m/z=420 (M+1); Rt=5.5 min.

Reference： [1]Patent: US2004/138301,2004,A1

15
[ 393-11-3 ]
[ 161622-05-5 ]
[ 691887-57-7 ]

Yield	Reaction Conditions	Operation in experiment
		Example 65 (General Procedure (D)) 3-Fluoro-N-(4-Nitro-3-Trifluoromethyl-Phenyl)-5-Trifluoromethyl-Benzamide. The title compound was prepared from <strong>[161622-05-5]3-fluoro-5-trifluoromethyl-benzoic acid</strong> and 4-nitro-3-trifluoromethylanilin. 1H NMR (DMSO-d6): delta ppm 8.05 (d, 1 H) 8.16 (d, 1 H) 8.21 (s, 1 H) 8.32 (m, 2 H) 8.43 (d, J=1.88 Hz, 1 H) 11.18 (s, 1 H); HPLC-MS (Method A): m/z=397 (M+1); Rt=5.0 min.

Reference： [1]Patent: US2004/138301,2004,A1

16
[ 1024583-36-5 ]
[ 161622-05-5 ]
[ 1024583-62-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 2324 - 2328

17
[ 161622-05-5 ]
[ 53985-48-1 ]

Yield	Reaction Conditions	Operation in experiment
	With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; sodium methylate; at 120℃;	(i) 3-methoxy-5-(trifluoromethyl)benzoic acid Sodium methoxide (13.0 g) was added to a stirred solution of <strong>[161622-05-5]3-fluoro-5-trifluoromethyl benzoic acid</strong> (25.0 g) in DMPU (200 ml) and heated at 120 C. overnight. The reaction was poured onto 2M HCl (800 ml). The resulting solid formed was filtered and washed with water, then dried in vacuo to give the subtitle compound (23.0 g). 1H NMR DMSO-d6: 7.75 (1H, s), 7.70 (1H, s), 7.51 (1H, s), 3.90 (3H, s).

Reference： [1]Patent: US2008/293775,2008,A1 .Location in patent: Page/Page column 24

18
C₁₀H₁₂N₃O₃Pol [ No CAS ]
[ 161622-05-5 ]
C₁₈H₁₄F₄N₃O₄Pol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 2,3,4-lutidine; HATU; In dichloromethane; at 20℃; for 2h;	A solution of <strong>[161622-05-5]3-fluoro-5-trifluoromethyl-benzoic acid</strong> (17.2 mg, 0.083mol) HATU (31.5 mg, 0.083 mmol) and collidine (45.4 muL, 0.345 mmol) in DCM (1 mL) was added to resin- bound (R)-4-(l-(hydrazinecarboxamido)ethyl)benzoic acid (106 mg, 0.069 mmol). The mixture was shaken 2 h at RT. The resin was filtered, washed with DMF (4 x 2 mL), methanol (4 x 2 mL) and DCM (4 x 2 mL) and suspended in DCM (1 mL) and TFA (1 mL). The suspension was shaken at RT for 30 minutes. The resin was filtered and washed with DCM (2 x 2 mL). The filtrate was concentrated in vacuo. The residue was purified by reversed phase HPLC using a gradient of ACN in water with 0.1% TFA to give the title compound. MS (m/z): 413.8 [M+H*]

Reference： [1]Patent: WO2009/36996,2009,A2 .Location in patent: Page/Page column 102-103

19
C₁₁H₁₄N₃O₃Pol [ No CAS ]
[ 161622-05-5 ]
C₁₉H₁₆F₄N₃O₄Pol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 2,3,4-lutidine; HATU; In dichloromethane; N,N-dimethyl-formamide; at 20℃; for 4h;	Phosgene (20% solution in toluene, 3.43 ml, 6.51 mmol) was added dropwise at 100C to a stirred solution of iV-methyl-hydrazinecarboxylic acid 9i/-fluoren-9-ylmethyl ester (1.81 g, 3.26 mmol) in dioxane (15 ml). The mixture was stirred at 1O0C for 5 minutes and then stirred at RT for 1.5 h. The mixture was concentrated in vacuo to give (9itf-fluoren-9-yl)methyl 2- (chlorocarbonyl)-2-methylhydrazinecarboxylate. The crude product (68.5 mg, 0.207 mmol) was dissolved in DCM (1 mL) and added to a suspension of resin-bound (R)-4-(l-amino- ethyl)-benzoic acid (106 mg, 0.069 mmol), swollen in DCM (5 mL) and collidine (136 muL, 1.035 mmol). The mixture was shaken 90 minutes at RT. The resin was filtered and washed with DMF (4 x 2 mL), methanol (4 x 2 mL) and DCM (4 x 2 mL). A test cleavage with TFA showed the right product (R)-4-(l-(2-(((9/-r-fluoren-9-yl)methoxy)carbonyl)-l- methylhydrazinecarboxamido)ethyl)benzoic acid. MS (m/z): 459.8 [M+H*]. Piperidin (20% solution in DMF, 4 mL) was added and the mixture was shaken for 30 minutes to give resin- bound (R)-4-(l-(l-methylhydrazinecarboxamido)ethyl)benzoic acid. The resin was filtered, washed with DMF (4 x 2 mL), methanol (4 x 2 mL) and DCM (4 x 2 mL) and a solution of 3- fluoro-5-trifluoromethyl-benzoic acid (17.2 mg, 0.083 mmol), HATU (31.5 mg, 0.083 mmol) and collidine (45.4 muL, 0.345 mmol) in DCM/DMF 2:1 (1.5 ml) was added. The mixture was shaken 4 h at RT. The resin was filtered, washed with DMF (4 x 2 mL), methanol (4 x 2 mL) and DCM (4 x 2 mL) and suspended in DCM (1 mL) and TFA (1 mL). The suspension was shaken at RT for 20 minutes. The resin was filtered and washed with DCM (2 x 2 mL). The filtrate was concentrated in vacuo. The residue was purified by reversed phase HPLC using a gradient of ACN in water with 0.1% TFA to give the title compound. MS (m/z): 427.7 [M+H+]

Reference： [1]Patent: WO2009/36996,2009,A2 .Location in patent: Page/Page column 104

20
[ 1134777-65-3 ]
[ 161622-05-5 ]
[ 1134775-83-9 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃;	To ter/-Butyl 2-((R)-l-(3-chloro-5-((2R,5S)-2,5-dimethylpyrrolidine-l-carbonyl)pyridin- 2-yl)ethylcarbamoyl)-2-ethylhydrazinecarboxylate (180 mg, 0.39 mmol) is added a solution of HCl in MeOH (3N, 20 mL). The reaction mixture is stirred at RT for 13 h and then concentrated to dryness. No purification step is required, and the isolated hydrochloride is <n="116"/>utilized in the next reaction.N-(I[Ry 1 -(3-Chloro-5-((2R,5-S)-2,5-dimethylpyrrolidine-l -carbonyl)pyridin-2-yl)ethyl)- 1 - ethylhydrazinecarboxamide hydrochloride (8.0 mg, 0.02 mmol) was added to a stirred solution of <strong>[161622-05-5]3-fluoro-5-(trifluoromethyl)benzoic acid</strong> (9.1 mg, 0.04 mmol), WSC (8.3 mg, 0.04 mmol), HOBt (5.9 mg, 0.04 mmol) and DIPEA (19 muL, 0.11 mmol) in DMF (0.2 mL). After stirring overnight at RT the residue was purified by reversed phase HPLC using a gradient of ACN in water with 0.1% TFA to give the title compound. MS (m/z): 557.9 [M+H*]

Reference： [1]Patent: WO2009/36996,2009,A2 .Location in patent: Page/Page column 114-115

21
[ 1134777-66-4 ]
[ 161622-05-5 ]
[ 1134775-86-2 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃;	To (R)-tert-buty 2-(l-(3-chloro-5-(diethylcarbamoyl)pyridin-2-yl)ethylcarbamoyl)-2- ethylhydrazinecarboxylate (93 mg, 0.21 mmol) is added a solution of HCl in MeOH (3N, 15 <n="117"/>mL). The reaction mixture is stirred at RT f 3 h and then concentrated to dryness. No purification step is required, and the isolated hydrochloride is utilized in the next reaction.(R)-5-Chloro-iV^V-diethyl-6-(l -( 1 -ethylhydrazinecarboxamido)ethyl)nicotinamide hydrochloride (8.3 mg, 0.02 mmol) was added to a stirred solution of 3-fluoro-5- (trifluoromethyl)benzoic acid (10 mg, 0.05 mmol), WSC (9.3 mg, 0.05 mmol), HOBt (6.6 mg, 0.05 mmol) and DIPEA (22 muL, 0.12 mmol) in DMF (0.2 mL). After stirring overnight at RT the residue was purified by reversed phase HPLC using a gradient of ACN in water with 0.1% TFA to give the title compound. MS (m/z): 531.8 [M+H*]

Reference： [1]Patent: WO2009/36996,2009,A2 .Location in patent: Page/Page column 115-116

22
C₁₂H₁₅FN₃O₃Pol [ No CAS ]
[ 161622-05-5 ]
C₂₀H₁₇F₅N₃O₄Pol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 2,3,4-lutidine; HATU; In dichloromethane; N,N-dimethyl-formamide; at 20℃; for 4h;	Phosgene (20% solution in toluene, 0.463 ml, 0.88 mmol) was added dropwise at 00C to a stirred solution of (9H-fluoren-9-yl)methyI 2-ethylhydrazinecarboxylate (125 mg, 0.44 mmol) in DCM (4.4 ml). The mixture was stirred at 00C for 30 minutes and then concentrated in vacuo to give (9H-fIuoren-9-yl)methyl 2-(chlorocarbonyl)-2-ethylhydrazinecarboxylate. The crude product (68.5 mg, 0.207 mmol) was dissolved in DCM (1 mL) and added to a suspension of resin-bound (R)-4-(l-aminoethyl)-3-fluorobenzoic acid (106 mg, 0.069 mmol), swollen in DCM (5 mL) and collidine (136 muL, 1.035 mmol). The mixture was shaken 90 minutes at RT. The resin was filtered and washed with DMF (4 x 2 mL), methanol (4 x 2 mL) and DCM (4 x 2 mL). A test cleavage with TFA showed the right product (R)-4-(l-(2-(((9//- <n="119"/>fluoren-9-yl)methoxy)carbonyl)- 1 -ethy lhydraz arboxamido)ethyl)-3 -fluorobenzoic acid. MS (m/z): 491.7 [M-I-H+]. Piperidin (20% solution in DMF, 4 mL) was added and the mixture was shaken for 30 min to give resin-bound (R)-4-(l-(l-ethylhydrazinecarboxamido)ethyl)-3- fluorobenzoic acid. The resin was filtered, washed with DMF (4 x 2 mL), methanol (4 x 2 mL) and DCM (4 x 2 mL) and a solution of <strong>[161622-05-5]3-fluoro-5-trifluoromethyl-benzoic acid</strong> (17.2 mg, 0.083mol), HATU (31.5 mg, 0.083 mmol) and collidine (45.4 muL, 0.345 mmol) in DCM/DMF 2:1 (1.5 ml) was added. The mixture was shaken 4 h at RT. The resin was filtered, washed with DMF (4 x 2 mL), methanol (4 x 2 mL) and DCM (4 x 2 mL) and suspended in DCM (1 mL) and TFA (1 mL). The suspension was shaken at RT for 20 minutes. The resin was filtered and washed with DCM (2 x 2 mL). The filtrate was concentrated in vacuo. The residue was purified by reversed phase HPLC using a gradient of ACN in water with 0.1% TFA to give the title compound. MS (m/z): 459.6 [M+H*]

Reference： [1]Patent: WO2009/36996,2009,A2 .Location in patent: Page/Page column 117-118

23
C₁₁H₁₄FN₃O₃ [ No CAS ]
[ 161622-05-5 ]
[ 1217794-49-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 1225 - 1228

24
C₁₃H₁₈FN₃O₃ [ No CAS ]
[ 161622-05-5 ]
[ 1217794-50-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 1225 - 1228

25
C₁₃H₁₈FN₃O₃ [ No CAS ]
[ 161622-05-5 ]
[ 1217794-51-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 1225 - 1228

26
C₁₃H₁₈FN₃O₃ [ No CAS ]
[ 161622-05-5 ]
[ 1217794-52-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 1225 - 1228

27
C₁₂H₁₆FN₃O₃ [ No CAS ]
[ 161622-05-5 ]
[ 1217794-53-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 1225 - 1228

28
C₁₄H₂₀FN₃O₃ [ No CAS ]
[ 161622-05-5 ]
[ 1217794-54-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 1225 - 1228

29
[ 1134776-42-3 ]
[ 161622-05-5 ]
[ 1217794-55-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 1225 - 1228

30
C₁₄H₁₇FN₂O₃ [ No CAS ]
[ 161622-05-5 ]
[ 1134776-74-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 1225 - 1228

31
C₁₃H₁₆FN₃O₃ [ No CAS ]
[ 161622-05-5 ]
[ 1217794-56-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 1225 - 1228

32
[ 746670-79-1 ]
[ 161622-05-5 ]
[ 746668-42-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 2425 - 2430

33
[ 951895-34-4 ]
[ 161622-05-5 ]
[ 1244694-60-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 4795 - 4799

34
[ 494769-44-7 ]
[ 161622-05-5 ]
[ 1363397-22-1 ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 0 - 20℃; for 8h;	General procedure: The intermediate (3) (0.5 g, 0.00217 mol), EDCl (0.622 g, 0.00325 mol), DMAP (0.345 g, 0.0028 mol) were stirred in dichloromethane (6 mL) at 0 C, and the substituted acid (0.00217 mol) were dissolved in (4 mL) of dichloromethane and charged to the reaction mixture and stirred at room temperature for 8 h. The reaction completion was monitored by TLC. Reaction was completed. The reaction mixture was diluted with (10 mL) of dichloromethane, and was washed with 10% NaHCO3 (10 mL). Separated the organic layer and was washed with saturated brine solution (10 mL). The organic layer was dried over sodium sulfate and concentrated the organic layer under reduced pressure to afford compounds 4a-t. The spectral data of compounds 4(a-t) are given below.

Reference： [1]European Journal of Medicinal Chemistry,2012,vol. 49,p. 172 - 182

35
[ 802983-60-4 ]
[ 161622-05-5 ]
N-{1-[6,6-bis-(4-fluoro-phenyl)-hexanoyl]-pyrrolidin-3-ylmethyl}-3-fluoro-5-trifluoromethyl-benzamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4153 - 4158

36
[ 1384171-37-2 ]
[ 161622-05-5 ]
[ 1384170-93-7 ]

Yield	Reaction Conditions	Operation in experiment
89%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 20℃;	Example 1; 3-(3-Fluoro-5-trifluoromethyl-benzoylamino)-oxetane-3-carboxylic acid ((R)-1-{5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-3-fluoro-pyridin-2-yl}-ethyl)-amide 3-Amino-oxetane-3-carboxylic acid ((R)-1-{5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-3-fluoro-pyridin-2-yl}-ethyl)-amide (30.0 mg, 0.0667 mmol, intermediate 1) was dissolved in dry DMF (1.5 ml) and <strong>[161622-05-5]3-fluoro-5-(trifluoromethyl)benzoic acid</strong> (17.0 mg, 0.0800 mmol), 1-hydroxybenzotriazole hydrate (11.2 mg, 0.0734 mmol), triethylamine (13.5 mg, 18.5 mul, 0.133 mmol) and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (26.0 mg, 0.133 mmol) were added. The colorless solution was stirred at room temperature overnight. Then water was added and the mixture was extracted three times with EtOAc. The combined organic layers were washed with sat. NaHCO3 solution, sat. NH4Cl solution, water and brine, dried with Na2SO4 and evaporated.The remaining light yellow gum was purified by chromatography (silica gel; DCM/MeOH 98:2) and the title compound was obtained as white foam (38 mg, 89%). MS: 640.1 [M+H]+.
89%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 20℃;	Example 1 3-(3-Fluoro-5-trifluoromethyl-benzoylamino)-oxetane-3-carboxylic acid ((R)-l-{5-[5- chloro-3 -fluoro-2-(5-methyl- [ 1 ,2,4] oxadiazol-3 -yl)-phenyl] -3 -fluoro-pyridin-2-yl } -ethyl)- amide3-Amino-oxetane-3-carboxylic acid ((R)-l-{5-[5-chloro-3-fluoro-2-(5-methyl- [l,2,4]oxadiazol-3-yl)-phenyl]-3-fluoro-pyridin-2-yl}-ethyl)-amide (30.0 mg, 0.0667 mmol, intermediate 1) was dissolved in dry DMF (1.5 ml) and 3-fluoro-5- (trifluoromethyl)benzoic acid (17.0 mg, 0.0800 mmol), 1-hydroxybenzotriazole hydrate (11.2 mg, 0.0734 mmol), triethylamine (13.5 mg, 18.5 mu, 0.133 mmol) and N-(3- dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (26.0 mg, 0.133 mmol) were added. The colorless solution was stirred at room temperature overnight. Then water was added and the mixture was extracted three times with EtOAc. The combined organic layers were washed with sat. NaHC03 solution, sat. NH4C1 solution, water and brine, dried with Na2S04 and evaporated.The remaining light yellow gum was purified by chromatography (silica gel; DCM / MeOH 98:2) and the title compound was obtained as white foam (38 mg, 89%). MS: 640.1 [M+H]+.

Reference： [1]Patent: US2012/165338,2012,A1 .Location in patent: Page/Page column 24
[2]Patent: WO2012/89601,2012,A1 .Location in patent: Page/Page column 59

37
[ 7154-73-6 ]
[ 161622-05-5 ]
[ 1415400-84-8 ]

Yield	Reaction Conditions	Operation in experiment
92%	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine; In dichloromethane; acetonitrile; at 20℃;	General procedure: A mixture of 1 mmol (1 equiv.) of carboxylic acids, 1.4 mmol (1.4 equiv.) of amine, 552 mg (1.8 equiv.) of PyBOP and 2 mL of triethylamine was stirred overnight at room temperature in 40 ml of a 1:1 mixture of CH2Cl2 and CH3CN. After solvent evaporation, the crude product was purified by column chromatography on silica (CHCl3:CH3CH2OH = 9:1) resulting in yellow thick oil that slowly crystallized.

Reference： [1]European Journal of Medicinal Chemistry,2012,vol. 57,p. 211 - 216

38
[ 30433-91-1 ]
[ 161622-05-5 ]
[ 1370339-91-5 ]

Yield	Reaction Conditions	Operation in experiment
97%	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine; In dichloromethane; acetonitrile; at 20℃;	General procedure: A mixture of 1 mmol (1 equiv.) of carboxylic acids, 1.4 mmol (1.4 equiv.) of amine, 552 mg (1.8 equiv.) of PyBOP and 2 mL of triethylamine was stirred overnight at room temperature in 40 ml of a 1:1 mixture of CH2Cl2 and CH3CN. After solvent evaporation, the crude product was purified by column chromatography on silica (CHCl3:CH3CH2OH = 9:1) resulting in yellow thick oil that slowly crystallized.

Reference： [1]European Journal of Medicinal Chemistry,2012,vol. 57,p. 211 - 216

39
[ 64-04-0 ]
[ 161622-05-5 ]
[ 1415400-90-6 ]

Yield	Reaction Conditions	Operation in experiment
95%	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine; In dichloromethane; acetonitrile; at 20℃;	General procedure: A mixture of 1 mmol (1 equiv.) of carboxylic acids, 1.4 mmol (1.4 equiv.) of amine, 552 mg (1.8 equiv.) of PyBOP and 2 mL of triethylamine was stirred overnight at room temperature in 40 ml of a 1:1 mixture of CH2Cl2 and CH3CN. After solvent evaporation, the crude product was purified by column chromatography on silica (CHCl3:CH3CH2OH = 9:1) resulting in yellow thick oil that slowly crystallized.

Reference： [1]European Journal of Medicinal Chemistry,2012,vol. 57,p. 211 - 216

40
[ 1201-74-7 ]
[ 161622-05-5 ]
[ 1415400-93-9 ]

Yield	Reaction Conditions	Operation in experiment
95%	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine; In dichloromethane; acetonitrile; at 20℃;	General procedure: A mixture of 1 mmol (1 equiv.) of carboxylic acids, 1.4 mmol (1.4 equiv.) of amine, 552 mg (1.8 equiv.) of PyBOP and 2 mL of triethylamine was stirred overnight at room temperature in 40 ml of a 1:1 mixture of CH2Cl2 and CH3CN. After solvent evaporation, the crude product was purified by column chromatography on silica (CHCl3:CH3CH2OH = 9:1) resulting in yellow thick oil that slowly crystallized.

Reference： [1]European Journal of Medicinal Chemistry,2012,vol. 57,p. 211 - 216

41
[ 4572-03-6 ]
[ 161622-05-5 ]
[ 1415400-82-6 ]

Yield	Reaction Conditions	Operation in experiment
75%	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine; In dichloromethane; acetonitrile; at 20℃;	General procedure: A mixture of 1 mmol (1 equiv.) of carboxylic acids, 1.4 mmol (1.4 equiv.) of amine, 552 mg (1.8 equiv.) of PyBOP and 2 mL of triethylamine was stirred overnight at room temperature in 40 ml of a 1:1 mixture of CH2Cl2 and CH3CN. After solvent evaporation, the crude product was purified by column chromatography on silica (CHCl3:CH3CH2OH = 9:1) resulting in yellow thick oil that slowly crystallized.

Reference： [1]European Journal of Medicinal Chemistry,2012,vol. 57,p. 211 - 216

42
[ 3731-53-1 ]
[ 161622-05-5 ]
[ 1415400-88-2 ]

Yield	Reaction Conditions	Operation in experiment
90%	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine; In dichloromethane; acetonitrile; at 20℃;	General procedure: A mixture of 1 mmol (1 equiv.) of carboxylic acids, 1.4 mmol (1.4 equiv.) of amine, 552 mg (1.8 equiv.) of PyBOP and 2 mL of triethylamine was stirred overnight at room temperature in 40 ml of a 1:1 mixture of CH2Cl2 and CH3CN. After solvent evaporation, the crude product was purified by column chromatography on silica (CHCl3:CH3CH2OH = 9:1) resulting in yellow thick oil that slowly crystallized.

Reference： [1]European Journal of Medicinal Chemistry,2012,vol. 57,p. 211 - 216

43
[ 2038-03-1 ]
[ 161622-05-5 ]
[ 1415400-80-4 ]

Yield	Reaction Conditions	Operation in experiment
70%	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; triethylamine; In dichloromethane; acetonitrile; at 20℃;	General procedure: A mixture of 1 mmol (1 equiv.) of carboxylic acids, 1.4 mmol (1.4 equiv.) of amine, 552 mg (1.8 equiv.) of PyBOP and 2 mL of triethylamine was stirred overnight at room temperature in 40 ml of a 1:1 mixture of CH2Cl2 and CH3CN. After solvent evaporation, the crude product was purified by column chromatography on silica (CHCl3:CH3CH2OH = 9:1) resulting in yellow thick oil that slowly crystallized.

Reference： [1]European Journal of Medicinal Chemistry,2012,vol. 57,p. 211 - 216

44
N-(5-amino-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide hydrochloride [ No CAS ]
[ 161622-05-5 ]
[ 1351237-39-2 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; HATU;	Preparation analogous to the general procedure by using <strong>[161622-05-5]3-fluoro-5-(trifluoromethyl)benzoicacid</strong> (1.1 eq), HATU (1.2 eq), DIPEA (5 eq). The crude compound was triturated with acetonitrile to give the title compound N-(5-(3-fluoro-5-(trifluoromethyl)benzamido)-2-methylphenyl)thieno[2,3-b]pyrazine-6-carboxamide 32f (6.8 mg, 16%). NMR (400 MHz, DMSO) 2.27 (s, 3H), 7.33 (d, J=8.2 Hz, 1H), 7.64 (dd, J=8.2 and 2.3 Hz, 1H), 7.89 (d, J=1.9, 1H), 7.98 (d, J=8.6, 1H), 8.14 (d, J=9.3 Hz, 1H), 8.19 (s, 1H), 8.54 (br s, 1H), 8.76 (d, J=2.3 Hz, 1H), 8.88 (d, J=2.3 Hz, 1H), 10.53 (br s, 1H), 10.57 (br s, 1H). (m/z)=475 (M+H)+.

Reference： [1]Patent: US2013/79341,2013,A1 .Location in patent: Paragraph 0176; 0177

45
[ 1429293-61-7 ]
[ 161622-05-5 ]
[ 1429292-16-9 ]

Yield	Reaction Conditions	Operation in experiment
33%	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 2h;	Example 273[00290] A mixture of Example 273A (12 mg, 0.025 mmol), <strong>[161622-05-5]3-fluoro-5-(trifluoromethyl)benzoic acid</strong> (8 mg, 0.04 mmol) and PyBOP (14 mg, 0.027 mmol) and DIPEA (0.013 mL, 0.074 mmol) in DCM (1.5 mL) was stirred at rt for 2 h. The reaction mixture was concentrated, and the residue was dissolved on MeOH and purified by reverse phase preparative HPLC (Method U) to afford Example 273 (5.0 mg, 8.0 muiotaetaomicron, 33 % yield) as a white solid. HPLC/MS (Method L) RT = 2.2 min, [M+H)+ = 576.0; XH NMR (400 MHz, CHLOROFORM-d) delta ppm 7.84 (1 H, s), 7.68 (1 H, d, J=8.53 Hz), 7.42 (1 H, d, J=7.78 Hz), 7.28 - 7.35 (2 H, m), 7.01 (1 H, dd, J=8.28, 2.01 Hz), 6.16 (1 H, d, J=8.53 Hz), 4.06 - 4.22 (3 H, m), 3.77 - 3.85 (2 H, m), 3.67 - 3.77 (2 H, m), 2.56 - 2.73 (2 H, m), 1.72 - 1.90 (2 H, m), 1.23 (3 H, d, J=6.53 Hz).

Reference： [1]Patent: WO2013/48982,2013,A1 .Location in patent: Paragraph 00290

46
[ 1235491-93-6 ]
[ 161622-05-5 ]
[ 1555543-66-2 ]

Yield	Reaction Conditions	Operation in experiment
80%		General procedure: A mixture of phenyl acid (0.001mol), EDCl (0.003mol), HOBt (0.002mol), Triethylamine (0.006mol) and dichloromethane (5.0mL) was stirred vigorously for 10min at ambient temperature. Then amine (5) (0.0022mol) in dichloromethane was added slowly to the reaction mixture. The reaction mass was stirred at ambient temperature for 4h. The reaction completion was monitored by TLC. After completion, the reaction mass was diluted with dichloromethane, washed with 10% NaHCO3 (10mL), brine solution. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified on a Biotage parallel column purifier using ethyl acetate: petroleum ether (3:1) as eluant to methanol: methylene chloride (2-6%). The spectral data of compounds 6(a-o) are given below.

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 71,p. 354 - 365

47
[ 161622-05-5 ]
[ 53985-39-0 ]