486460-20-2|3-(Trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyrazine| Ambeed

Size	Price	VIP Price	US Stock	Global Stock	In Stock
{[ item.pr_size ]}		Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

{[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

Quality Control of [ 486460-20-2 ] Purity: 95% SDS Specification

COA

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

NMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

CNMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

HPLC

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

LC-MS

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

1-2 Day Shipping
High Quality
Technical Support

Product Details of [ 486460-20-2 ]

CAS No. :	486460-20-2
Formula :	C₆H₃F₃N₄
M.W :	188.11
SMILES Code :	FC(C1=NN=C2C=NC=CN21)(F)F
MDL No. :	MFCD09029664
InChI Key :	HHRYGAGDPASJQP-UHFFFAOYSA-N
Pubchem ID :	29923462

Safety of [ 486460-20-2 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H320-H335
Precautionary Statements:	P261-P280-P301+P312-P302+P352-P305+P351+P338

Application In Synthesis of [ 486460-20-2 ]

* 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.

Upstream synthesis route of [ 486460-20-2 ]
Downstream synthetic route of [ 486460-20-2 ]

[ 486460-20-2 ] Synthesis Path-Upstream 1~4

1
[ 1447800-65-8 ]
[ 486460-20-2 ]

Yield	Reaction Conditions	Operation in experiment
90%	With triethylamine In toluene at 20℃; for 1 h;	General procedure: (10 mmole) of compound 3 was dissolved in 5 volume of toluene and to this was added (20 mmole) of triethylamine at ambient temperature, and stirred for 1hour. Progress of the reaction was monitored by TLC. After completion of the reaction the reaction mixture was poured on 25g of ice water layers were separated and the organic layer was washed with2X 10ml of cold water dried over sodium sulphate and concentrated to give compound 4 in excellent yield.

References: [1] Letters in Organic Chemistry, 2013, vol. 10, # 5, p. 348 - 352.

2
[ 54608-52-5 ]
[ 407-25-0 ]
[ 486460-20-2 ]

Yield	Reaction Conditions	Operation in experiment
65.1%	at 0 - 80℃; for 12 h;	2) 6.0 g (55 mmol) of 2-hydrazinopyrazine was added250 mL of three-necked flask,Ice water cooled to 0 ° C,Under the magnetic stirring, 28.6 g was slowly added dropwise(136 mmol) of trifluoroacetic anhydride,Then rose to room temperature for 2 hours,Add 35 ml of diluted polyphosphoric acid(Diluted 10 grams of water per 100 grams of polyphosphoric acid)Heated to 80 ° C for 10 hours,After cooling to room temperature,To the residue was added 30 ml of ice water,Slowly drop the sodium hydroxide solution to adjust the pH value of 7-8,Ethyl acetate extraction,Combined organic layer,The organic phase is saturatedSodium chloride aqueous solution,Dried over anhydrous sodium sulfate,Condensed organic layer,To give 6.7 g of a pale yellow solid,Yield 65.1percent.
50%	Stage #1: at 20℃; for 4 h; Stage #2: at 80℃; for 15 h;	A solution of 2-hydrazinopyrazine (1.10 g) in trifluoroacetic anhydride (10 mL) was stirred at room temperature for 4 h. To the mixture was added PPA (12 mL). The reaction mixture was heated at 80 °C for another 15 h. The reaction mixture was cooled to room temperature and filtered to afford the title compound as a white solid (0.94 g, 50.00 percent). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 189.0 (M+l); ? NMR (400 MHz, CDC1₃) ?: 8.64 (s, 3H).
50%	Stage #1: at 20℃; for 4 h; Stage #2: at 80℃; for 15 h;	A solution of 2-hydrazinopyrazine (1.10 g) in trifluoroacetic anhydride (10 mL) was stirred at room temperature for 4 h. To the mixture was added PPA (12 mL). The reaction mixture was heated at 80° C. for another 15 h. The reaction mixture was cooled to room temperature and filtered to afford the title compound as a white solid (0.94 g, 50.00percent). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 189.0 (M+1); ¹H NMR (400 MHz, CDCl₃) δ: 8.64 (s, 3H).

References: [1] Patent: CN106749262, 2017, A, . Location in patent: Paragraph 0036.
[2] Patent: WO2013/71697, 2013, A1, . Location in patent: Paragraph 00199.
[3] Patent: US2014/228361, 2014, A1, . Location in patent: Paragraph 0281-0282.

3
[ 54608-52-5 ]
[ 76-05-1 ]
[ 486460-20-2 ]

Yield	Reaction Conditions	Operation in experiment
861 mg	at 140℃; for 18 h;	A mixture of 2-hydrazinopyrazine (820 mg, 7.45 mmol), prepared from 2-chloropyrazine and hydrazine using a procedure analogous to that described in the literature (P. J. Nelson and K. T. Potts, J. Org. Chem. 1962, 27, 3243, except that the crude product was extracted into 10percent methanol/dichloromethane and filtered, and the filtrate was concentrated and purified by flash chromatography on silica gel, eluting with 100percent ethyl acetate followed by 10percent methanol in dichloromethane), TFA (2.55 g, 22.4 mmol), and polyphosphoric acid (10 mL) was heated to 140° C. with stirring for 18 h. The solution was added to ice and neutralized by the addition of ammonium hydroxide. The aqueous solution was extracted with ethyl acetate (3×), washed with brine, and dried over anhydrous magnesium sulfate. Concentration followed by flash chromatography (silica gel, 1:1 hexane:ethyl acetate, then 100percent ethyl acetate) afforded the title compound as a solid (861 mg). ¹H NMR (500 MHz, CDCl₃) δ 8.17-8.20 (m, 2H), 9.54 (s, 1H). LC/MS (M+1) 189

References: [1] Patent: WO2006/23750, 2006, A2, . Location in patent: Page/Page column 47.
[2] Patent: US2015/359793, 2015, A1, . Location in patent: Paragraph 0208.
[3] Patent: WO2004/58266, 2004, A1, . Location in patent: Page/Page column 87.

4
[ 1447800-62-5 ]
[ 486460-20-2 ]

References: [1] Letters in Organic Chemistry, 2013, vol. 10, # 5, p. 348 - 352.

[ 486460-20-2 ] Synthesis Path-Downstream 1~41

1
[ 486460-20-2 ]
7-[(3R)-3-amino-4-(2,5-difluorophenyl)butanoyl]-3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyrazine [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 141 - 151.

2
[ 486460-20-2 ]
[ 486460-32-6 ]

References: [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 141 - 151.

3
[ 486460-20-2 ]
[ 1025835-55-5 ]

References: [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 141 - 151.

4
[ 486460-20-2 ]
[ 486460-22-4 ]

References: [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 141 - 151.

5
[ 486460-20-2 ]
[ 486460-23-5 ]

References: [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 141 - 151.

6
[ 486460-20-2 ]
7-[(3R)-3-amino-4-(2,5-difluorophenyl)butanoyl]-3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3-a]pyrazine hydrochloride [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 141 - 151.

7
[ 486460-20-2 ]
3-amino-4-(3,4-difluoro-phenyl)-1-(3-trifluoromethyl-5,6-dihydro-8<i>H</i>-[1,2,4]triazolo[4,3-<i>a</i>]pyrazin-7-yl)-butan-1-one; hydrochloride [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 141 - 151.

8
[ 486460-20-2 ]
Sitagliptin hydrochloride [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 141 - 151.

9
[ 54608-52-5 ]
[ 76-05-1 ]
[ 486460-20-2 ]

Yield	Reaction Conditions	Operation in experiment
	With PPA; at 140℃; for 18h;	A sample of 2-hydrazinopyrazine was prepared from 2-chloropyrazine and hydrazineusing a procedure analogous to that described in the literature [P.J. Nelson and K.T. Potts, /. Org. Chem.,27. 3243 (1962)], except that the crude product was extracted into 10% methanol/dichloromethane andfiltered, and the filtrate was concentrated and purified by flash chromatography on silica gel, eluting with100% ethyl acetate followed by 10% methanol in dichloromethane. A mixture of 2-hydrazinopyrazine(820 mg, 7.45 mmol), trifluoroacetic acid (2.55 g, 22.4 mmol), and polyphosphoric acid (10 mL) washeated to 140 C with stirring for 18 h. The solution was added to ice and neutralized by the addition ofammonium hydroxide. The aqueous solution was extracted three times with ethyl acetate, washed withbrine, and dried over anhydrous magnesium sulfate. Concentration followed by flash chromatography(silica gel, 1:1 hexane:ethyl acetate, then 100% ethyl acetate) afforded the title compound as a solid.'H NMR (500 MHz, CDC13): 5 8.17-8.20 (m, 2H), 9.54 (s, 1H); C/MS 189 (M+l).
861 mg	With polyphosphoric acid; at 140℃; for 18h;	A mixture of 2-hydrazinopyrazine (820 mg, 7.45 mmol), prepared from 2-chloropyrazine and hydrazine using a procedure analogous to that described in the literature (P. J. Nelson and K. T. Potts, J. Org. Chem. 1962, 27, 3243, except that the crude product was extracted into 10% methanol/dichloromethane and filtered, and the filtrate was concentrated and purified by flash chromatography on silica gel, eluting with 100% ethyl acetate followed by 10% methanol in dichloromethane), TFA (2.55 g, 22.4 mmol), and polyphosphoric acid (10 mL) was heated to 140 C. with stirring for 18 h. The solution was added to ice and neutralized by the addition of ammonium hydroxide. The aqueous solution was extracted with ethyl acetate (3×), washed with brine, and dried over anhydrous magnesium sulfate. Concentration followed by flash chromatography (silica gel, 1:1 hexane:ethyl acetate, then 100% ethyl acetate) afforded the title compound as a solid (861 mg). 1H NMR (500 MHz, CDCl3) delta 8.17-8.20 (m, 2H), 9.54 (s, 1H). LC/MS (M+1) 189
	With PPA; at 140℃; for 18h;	A mixture of 2-hydrazinopyrazine (820 mg, 7.45 mmol), prepared from 2- chloropyrazine and hydrazine using a procedure analogous to that described in the literature (P. J. Nelson and K. T. Potts, J. Org. Chem. 1962, 27, 3243, except that the crude product was extracted into 10% methanol/dichloromethane and filtered, and the filtrate was concentrated and purified by flash chromatography on silica gel, eluting with 100% ethyl acetate followed by 10% methanol in dichloromethane), TFA (2.55 g, 22.4 mmol), and polyphosphoric acid (10 mL) was heated to 140 C with stirring for 18 h. The solution was added to ice and neutralized by the addition of ammonium hydroxide. The aqueous solution was extracted with ethyl acetate (3X), washed with brine, and dried over anhydrous magnesium sulfate. Concentration followed by flash chromatography (silica gel, 1: 1 hexane: ethyl acetate, then 100% ethyl acetate) afforded the title compound as a SOLID. 1H NMR (500 MHz, CDC13) 8 8. 17-8. 20 (m, 2H), 9.54 (s, 1H). LC/MS (M+1) 189.

References: [1]Patent: WO2006/23750,2006,A2 .Location in patent: Page/Page column 47.
[2]Patent: US2015/359793,2015,A1 .Location in patent: Paragraph 0208.
[3]Patent: WO2004/58266,2004,A1 .Location in patent: Page/Page column 87.

10
[ 486460-20-2 ]
[ 1078568-92-9 ]

Yield	Reaction Conditions	Operation in experiment
26%	With hydrogen; water-d2;palladium 10% on activated carbon; at 180℃; under 760.051 Torr; for 30.3333 - 30.5h;	Synthesis of 5,6,8-d3-<strong>[486460-20-2]3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyrazine</strong> (14). To a heavy walled glass pressure vessel charged with <strong>[486460-20-2]3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyrazine</strong> 13 (2.00 g, 10.6 mmol) and D2O (81.0 mL) was added 10% Pd/C (400 mg, 20 wt %). The vessel was then purged several times with N2 followed by H2 before allowing the reaction to stir under an H2 atmosphere (1 atmosphere) for 10-15 min. The vessel was then purged with N2, sealed, and the reaction stirred at 180 C. for 15 h. At this time additional D2O (5.00 mL) and 10% Pd/C (400 mg, 20 wt %) were added and the vessel was again purged several times with N2 followed by H2 before allowing the reaction to stir under an H2 atmosphere (1 atmosphere) for 10-15 min. The vessel was then purged with N2, sealed, and the reaction stirred at 180 C. for an additional 15 h. Upon cooling to room temperature the reaction was filtered through Celite which was subsequently washed several times with ethyl acetate and water (alternating washes). The dark brown solution was then brought to pH >7 with saturated aqueous sodium bicarbonate, and extracted with ethyl acetate (3×200 mL). The organic layers were combined, washed with brine, dried (MgSO4), filtered and concentrated in vacuo to afford a dark brown oil. Purification via flash chromatography (gradient elution, 0-40% ethyl acetate/hexanes) afforded 14 (530 mg, 26%) as a brown crystalline solid. MS (M+H): 192.1.

References: [1]Patent: US2008/280913,2008,A1 .Location in patent: Page/Page column 11-12.

11
[ 54608-52-5 ]
[ 407-25-0 ]
[ 486460-20-2 ]

Yield	Reaction Conditions	Operation in experiment
65.1%	With polyphosphoric acid; at 0 - 80℃; for 12h;	2) 6.0 g (55 mmol) of 2-hydrazinopyrazine was added250 mL of three-necked flask,Ice water cooled to 0 C,Under the magnetic stirring, 28.6 g was slowly added dropwise(136 mmol) of trifluoroacetic anhydride,Then rose to room temperature for 2 hours,Add 35 ml of diluted polyphosphoric acid(Diluted 10 grams of water per 100 grams of polyphosphoric acid)Heated to 80 C for 10 hours,After cooling to room temperature,To the residue was added 30 ml of ice water,Slowly drop the sodium hydroxide solution to adjust the pH value of 7-8,Ethyl acetate extraction,Combined organic layer,The organic phase is saturatedSodium chloride aqueous solution,Dried over anhydrous sodium sulfate,Condensed organic layer,To give 6.7 g of a pale yellow solid,Yield 65.1%.
50%		A solution of 2-hydrazinopyrazine (1.10 g) in trifluoroacetic anhydride (10 mL) was stirred at room temperature for 4 h. To the mixture was added PPA (12 mL). The reaction mixture was heated at 80 C for another 15 h. The reaction mixture was cooled to room temperature and filtered to afford the title compound as a white solid (0.94 g, 50.00 %). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 189.0 (M+l); ? NMR (400 MHz, CDC13) ?: 8.64 (s, 3H).
50%		A solution of 2-hydrazinopyrazine (1.10 g) in trifluoroacetic anhydride (10 mL) was stirred at room temperature for 4 h. To the mixture was added PPA (12 mL). The reaction mixture was heated at 80 C. for another 15 h. The reaction mixture was cooled to room temperature and filtered to afford the title compound as a white solid (0.94 g, 50.00%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 189.0 (M+1); 1H NMR (400 MHz, CDCl3) delta: 8.64 (s, 3H).

References: [1]Patent: CN106749262,2017,A .Location in patent: Paragraph 0036.
[2]Patent: WO2013/71697,2013,A1 .Location in patent: Paragraph 00199.
[3]Patent: US2014/228361,2014,A1 .Location in patent: Paragraph 0281-0282.

12
[ 486460-20-2 ]
[ 1438078-71-7 ]

References: [1]Patent: WO2013/71697,2013,A1 .
[2]Patent: US2014/228361,2014,A1 .

13
[ 486460-20-2 ]
[ 1438071-81-8 ]

References: [1]Patent: WO2013/71697,2013,A1 .
[2]Patent: US2014/228361,2014,A1 .

14
[ 1447800-62-5 ]
[ 486460-20-2 ]

References: [1]Letters in Organic Chemistry,2013,vol. 10,p. 348 - 352.

15
[ 1447800-65-8 ]
[ 486460-20-2 ]

Yield	Reaction Conditions	Operation in experiment
90%	With triethylamine; In toluene; at 20℃; for 1h;	General procedure: (10 mmole) of compound 3 was dissolved in 5 volume of toluene and to this was added (20 mmole) of triethylamine at ambient temperature, and stirred for 1hour. Progress of the reaction was monitored by TLC. After completion of the reaction the reaction mixture was poured on 25g of ice water layers were separated and the organic layer was washed with2X 10ml of cold water dried over sodium sulphate and concentrated to give compound 4 in excellent yield.

References: [1]Letters in Organic Chemistry,2013,vol. 10,p. 348 - 352.

16
[ 486460-20-2 ]
[ 762240-92-6 ]

Yield	Reaction Conditions	Operation in experiment
82.9%		A mixture of compound 10 (12.0 g, 0.064 mol) and the catalyst,Pd/C (10% w/w, 120.0 mg) in methanol (MeOH)(120 mL) was charged into an autoclave (500 mL) at ambienttemperature. The reaction mass was agitated for 24 h bymaintaining 3.5-4.5 Kg/cm2 hydrogen pressure at 40-45 C.The completion of reaction was judged by TLC. The reactionmass was concentrated under reduced pressure afterremove the Pd/C catalyst by passing through celite undernitrogen atmosphere. The residue was dissolved in IPA(24.0 mL) and then IPA.HCl (24.0 mL) was added slowly at 0-5 C. The precipitated solid was separated by filtration,after one hour agitation of the reaction mass, to obtain 3-trifluoromethyl)-5,6,7,8-tetrahydro-1,2,4-triazolo-[4,3-a]pyrazinehydrochloride (11) as a white crystalline solid (12.1 g, 82.9%).m.p.: 237-249 C (Lit. 236-246 C reported in chemical book).1H NMR (400MHz; DMSO-d6), d, ppm (J, Hz): 3.65 (2H, t,J5.6, Piperazine); 4.46 (2H, t, J5.6, Piperazine); 4.61(2H, s, Piperazine); 10.58 (2H, br, NH2). 13C NMR(100MHz; DMSO-d6) d, ppm (J, Hz): 39.09 (-CH2-CH2-),40.14 (-CH2-CH2-), 40.90 (-CH2-), 117.17 (d, J268.4, CF3),142.29 (C triazole), 148.73 (C triazole). LC-MS m/z (rel, %):193.08 (M+H)+ (100).

References: [1]Phosphorus, Sulfur and Silicon and the Related Elements,2019,vol. 194,p. 922 - 932.
[2]Organic Process Research and Development,2005,vol. 9,p. 634 - 639.
[3]Journal of Heterocyclic Chemistry,2019,vol. 56,p. 434 - 442.

17
(1,2)-bis-trifluoroacetyl-1-pyrazinylhydrazide [ No CAS ]
[ 486460-20-2 ]

References: [1]Organic Process Research and Development,2005,vol. 9,p. 634 - 639.
[2]Journal of Heterocyclic Chemistry,2019,vol. 56,p. 434 - 442.

18
2,2,2-trifluoro-N′-(pyrazin-2-yl)acetohydrazide [ No CAS ]
[ 486460-20-2 ]

Yield	Reaction Conditions	Operation in experiment
67.3%	With sulfuric acid; at 0 - 85℃; for 12h;	To the solution of concentrated H2SO4 (20.0 mL), compound9 (20.0 g, 0.097 mol) was added in a portion-wise at 0-5 C and then the reaction mass was stirred for 12 h at 80-85 C. After completion of the reaction that was checkedby TLC, DCM (120 mL) was added to the reaction mass atambient temperature and then the reaction mass wasquenched with 30% aqueous NaOH solution by maintainingtemperature at -5 to 5 C (Highly exothermic) up to attainthe mass pH to 8.0-10.0. The inorganic salts were separatedby filtration, and the solvent was removed from the organic layer under atmospheric conditions at below 45 C. Thecrude residue product was recrystallized from acetone:cyclohexane(1.5:6.5 v/v) to obtain, 3-(trifluoromethyl)-1,2,4-triazolo[4,3-a]pyrazine (10) as a pale brown solid (12.4 g,67.3%). 1H NMR (400 MHz; CDCl3) d, ppm (J, Hz): 8.12-8.22 (2H, m, Ar-H); 9.43 (1H, s, Ar-H). ESI-MS m/z (rel,%): 189.03 (M+H+) (100). HRMS (FAB) Calc.: C6H3F3N4:188.0309816199; Found: 189.0309 [M+H+].
32%	With polyphosphoric acid; at 150℃; for 1h;	To title compound 477 (3.12 g, 15.14 mmol) was added PPA (15 mL). The mixture was heated to 150 C. for 1 h then poored over water. The aqueous was basified with conc. NH4OH (exotherm) at 0 C. Water was added until everything was dissolved. The mixture was extracted with ethyl acetate (×4). The organics were washed with brine, died over Na2SO4, filtered and concentrated to a brown paste. The residue was purified by flash chromatography (0% to 70% ethyl acetate in hexanes) to afford title compound 478 (0.9 g, 32%) as a brown solid. MS (m/z): 189.1 (M+H).

References: [1]Phosphorus, Sulfur and Silicon and the Related Elements,2019,vol. 194,p. 922 - 932.
[2]Patent: US2017/749,2017,A1 .Location in patent: Paragraph 0715.

19
[ 486460-20-2 ]
ethyl 2-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)pyrimidine-5-carboxylate [ No CAS ]

References: [1]Patent: US2017/749,2017,A1 .

20
[ 486460-20-2 ]
7-(4-nitrobenzyl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine [ No CAS ]