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[ CAS No. 4928-87-4 ] {[proInfo.proName]}

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2D 3D

Chemical Structure| 4928-87-4

Chemical Structure| 4928-87-4

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Quality Control of [ 4928-87-4 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 4928-87-4 ]

Product Details of [ 4928-87-4 ]

CAS No. :	4928-87-4	MDL No. :	MFCD00078268
Formula :	C₃H₃N₃O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	LJVQHXICFCZRJN-UHFFFAOYSA-N
M.W :	113.07	Pubchem ID :	295900
Synonyms :

Calculated chemistry of [ 4928-87-4 ]

Physicochemical Properties

Num. heavy atoms :	8
Num. arom. heavy atoms :	5
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	4.0
Num. H-bond donors :	2.0
Molar Refractivity :	23.34
TPSA :	78.87 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.1 cm/s

Lipophilicity

Log Po/w (iLOGP) :	-0.51
Log Po/w (XLOGP3) :	-0.15
Log Po/w (WLOGP) :	-0.5
Log Po/w (MLOGP) :	-1.28
Log Po/w (SILICOS-IT) :	0.2
Consensus Log Po/w :	-0.45

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-0.84
Solubility :	16.2 mg/ml ; 0.144 mol/l
Class :	Very soluble
Log S (Ali) :	-1.05
Solubility :	10.0 mg/ml ; 0.0888 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.18
Solubility :	75.1 mg/ml ; 0.664 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.45

Safety of [ 4928-87-4 ]

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 [ 4928-87-4 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 4928-87-4 ]
Downstream synthetic route of [ 4928-87-4 ]

[ 4928-87-4 ] Synthesis Path-Upstream 1~1

1
[ 67-56-1 ]
[ 4928-87-4 ]
[ 4928-88-5 ]

Reference： [1] Russian Journal of Bioorganic Chemistry, 2013, vol. 39, # 1, p. 53 - 71[2] Bioorganicheskaya Khimiya, 2013, vol. 39, # 1, p. 61 - 80,20
[3] Gazzetta Chimica Italiana, 1991, vol. 121, # 6, p. 297 - 300

[ 4928-87-4 ] Synthesis Path-Downstream 1~88

1
[ 274-80-6 ]
[ 4928-87-4 ]

Reference： [1]Gazzetta Chimica Italiana,1991,vol. 121,p. 297 - 300

2
[ 67-56-1 ]
[ 4928-87-4 ]
[ 4928-88-5 ]

Reference： [1]Russian Journal of Bioorganic Chemistry,2013,vol. 39,p. 53 - 71
Bioorganicheskaya Khimiya,2013,vol. 39,p. 61 - 80,20
[2]Gazzetta Chimica Italiana,1991,vol. 121,p. 297 - 300

3
[ 913237-84-0 ]
[ 4928-87-4 ]
[ 913237-93-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2006,vol. 14,p. 7146 - 7153

4
[ 4928-87-4 ]
[ 51336-94-8 ]
[ 913237-92-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2006,vol. 14,p. 7146 - 7153

5
[ 4928-87-4 ]
[ 2631-72-3 ]
[ 913237-89-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2006,vol. 14,p. 7146 - 7153

6
[ 4928-87-4 ]
[ 2632-10-2 ]
[ 913237-88-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2006,vol. 14,p. 7146 - 7153

7
[ 4928-87-4 ]
[ 66122-32-5 ]
[ 913237-90-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2006,vol. 14,p. 7146 - 7153

8
[ 4928-87-4 ]
[ 70-11-1 ]
1-(2-oxo-2-phenyl-ethyl)-1<i>H</i>-[1,2,4]triazole-3-carboxylic acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2006,vol. 14,p. 7146 - 7153

9
[ 4928-87-4 ]
[ 456-04-2 ]
[ 913237-91-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2006,vol. 14,p. 7146 - 7153

10
[ 4928-87-4 ]
[ 2632-13-5 ]
1-[2-(4-methoxy-phenyl)-2-oxo-ethyl]-1<i>H</i>-[1,2,4]triazole-3-carboxylic acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2006,vol. 14,p. 7146 - 7153

11
[ 4928-87-4 ]
[ 64-17-5 ]
1H-1,2,4-triazole-3-carbocyclic acid ethyl ester hydrochloride [ No CAS ]

Reference： [1]Patent: EP1186599,2002,A1 .Location in patent: Page 23

12
[ 4928-87-4 ]
[ 7732-18-5 ]
lead(II) chloride [ No CAS ]
[Pb(3-carboxylic acid-4H-1,2,4-triazole(-H))(μ2-Cl)(H2O)](n) [ No CAS ]

Reference： [1]Inorganic Chemistry Communications,2008,vol. 11,p. 1481 - 1483

13
[ 4928-87-4 ]
C₃₆H₅₂N₁₀O₇ [ No CAS ]
C₃₉H₅₃N₁₃O₈ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 3175 - 3186

14
[ 4928-87-4 ]
C₃₉H₅₆N₁₀O₇ [ No CAS ]
C₄₂H₅₇N₁₃O₈ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 3175 - 3186

15
[ 4928-87-4 ]
[ 933998-46-0 ]
N-(6'-amino-3"-fluoro-3,2':3',4"-terpyridin-5'-yl)-1H-1,2,4-triazole-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%		A solution of 1H-<strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong> (0.072 g, 0.64 mmol), N- [(dimethylamino)(3H-[1 ,2,3]triazolo[4,5-b]pyridin-3-yloxy)methylene]-lambda/- methylmethanaminium hexafluorophosphate (0.243 g, 0.64 mmol) and lambda/-ethyl-lambda/- isopropylpropan-2-amine (0.205 mL, 1.17 mmol) in DMF (1.5 mL) was stirred for 15 minutes under argon. Finally, 3"-fluoro-3,2I:3l,4"-terpyridine-5',6I-diamine (Intermediate 1 , 0.15 g, 0.53 mmol) in DMF (3 mL) was added and the mixture was stirred at room temperature for 20 hours. The solvent was evaporated and the crude mixture was purified by silica gel flash chromatography (90:10 dichloromethane/methanol) to give the title compound (0.070 g, 35% of yield). ESI/MS m/e: 377 ([M+H]+, C18H13FN8O).

Reference： [1]Patent: WO2007/39297,2007,A1 .Location in patent: Page/Page column 69

16
[ 387362-37-0 ]
[ 4928-87-4 ]

Reference： [1]Heteroatom Chemistry,2010,vol. 21,p. 521 - 532

17
[ 1260230-04-3 ]
[ 4928-87-4 ]

Reference： [1]Heteroatom Chemistry,2010,vol. 21,p. 521 - 532

18
[ 1260230-06-5 ]
[ 4928-87-4 ]

Reference： [1]Heteroatom Chemistry,2010,vol. 21,p. 521 - 532

19
[ 1260230-07-6 ]
[ 4928-87-4 ]

Reference： [1]Heteroatom Chemistry,2010,vol. 21,p. 521 - 532

20
[ 1260230-09-8 ]
[ 4928-87-4 ]

Reference： [1]Heteroatom Chemistry,2010,vol. 21,p. 521 - 532

21
[ 1260230-10-1 ]
[ 4928-87-4 ]

Reference： [1]Heteroatom Chemistry,2010,vol. 21,p. 521 - 532

22
[ 4928-87-4 ]
anti-(8-azabicyclo[3.2.1]octan-3-yl)-3-(6-phenylpyridin-3-yl)-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidine [ No CAS ]
anti-(3-(3-(6-phenylpyridin-3-yl)-6,7,8,9-tetrahydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octan-8-yl)(4H-1,2,4-triazol-3-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 1h;	A mixture of 8-azabicyclo[3.2. l]octan-3-yl)-3-(6-phenylpyridin-3-yl)-6,7,8,9- tetrahydropyrazolo[l,5-a]pyrido[3,2-e]pyrimidine (73 mg, 0.17 mmoL), lH-l,2,4-triazole-3- carboxylic acid (22.7 mg, 0.20 mmoL), EDC (64.0 mg, 0.33mmoL), HOBt (45.2 mg, 0.33 mmoL) and DIEA (173.9 mu, 1.00 mmoL) in DMF (2 mL) was stirred at room temperature for lh. Purification with prep-LC provided (3-(3-(6-phenylpyridin-3-yl)-6,7>8,9- tetrahydropyrazolo[l ,5-a]pyrido[3,2-e]pyrimidin-5-yl)-8-azabicyclo[3.2.1 ]octan-8-yl)(4H- lf2,4-triazol-3-yl)methanone: LCMS tR = 2.48 Min (10 min run, UV254nm). Mass calculated for, M+ 531.2, observed LC/MS m/z 532.0 (M+H).

Reference： [1]Patent: WO2012/27240,2012,A1 .Location in patent: Page/Page column 58

23
[ 4928-87-4 ]
anti-5-(8-azabicyclo[3.2.1]octan-3-yl)-7-(6-phenylpyridin-3-yl)-2,4-dihydro-1H-[1,3]oxazino[5,4-e]pyrazolo[1,5-a]pyrimidine trifluoroacetate [ No CAS ]
anti-(3-(7-(6-phenylpyridin-3-yl)-2,4-dihydro-1H-[1,3]oxazino[5,4-e]pyrazolo[1,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octan-8-yl)(4H-1,2,4-triazol-3-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 0.166667h;	A mixture of lH-1 ,2,4-triazole-3-carboxylic acid (8 mg, 0.07 mmol), EDCI (20 mg, 0.1 mmol), and 1-hydroxybenzotriazole (9 mg, 0.07 mmol) in DMF (1 mL) was slightly warmed up to a homogeneous solution which was added into a stirred solution of 5~(8- azabicyclo [3.2.1 ]octan-3 -yl)-7-(6-phenylpyridin-3 -yl)-2,4-dihydro- 1 H-[ 1 ,3]oxazino[5 ,4- e]pyrazolo[l,5-a]pyrimidine TFA salt (0.07 mmol) and N,N-diisopropylethylamine (37 mu,, 0.2 mmol) in DMF (2mL). It was stirred further for 10 min at room temperature. This crude compound was purified by HPLC to afford (3-(7-(6-phenylpyridin-3-yl)-2,4-dihydro-l FIJI, 3]oxazino[5,4-e]pyrazolo[l,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2. l]octan-8-yl)(4H-l?2,4- triazol-3-yl)methanone. LCMS t = 3.20 Min (10 min run, UV254nm). Mass calculated for M+ H 534.0, observed LC/MS m/z 534.0 (M+H).

Reference： [1]Patent: WO2012/27240,2012,A1 .Location in patent: Page/Page column 54

24
[ 4928-87-4 ]
1-(2-tert-butylphenyl)piperazine dihydrochloride [ No CAS ]
[ 1252656-17-9 ]

Yield	Reaction Conditions	Operation in experiment
56%		Example 59 1-(2-tert-Butylphenyl)-4-(1H-1,2,4-triazol-3-ylcarbonyl)piperazine A mixture of 1-(2-tert-butylphenyl)piperazine dihydrochloride obtained in Reference Example 1 (0.30 g, 1.03 mmol), <strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong> (0.12 g, 1.08 mmol), triethylamine (0.22 g, 2.16 mmol), EDCI (0.21 g, 1.08 mmol) and HOBt (0.17 g, 1.08 mmol) in N,N-dimethylformamide (10 mL) was stirred at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure and the resulting residue was partitioned between ethyl acetate and water, and the suspension of white precipitate in ethyl acetate was washed with 10% sodium hydrogen carbonate solution, water, saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to afford white solid. This solid was triturated with diisopropyl ether to give the title compound (0.18 g, 56%) as a white solid, mp 295 C. 1H NMR (300 MHz, DMSO-d6) delta 1.42 (s, 9H), 2.63-3.11 (m, 5H), 3.18-3.47 (m, 1H), 4.38-4.79 (m, 2H), 7.02-7.29 (m, 2H), 7.28-7.47 (m, 2H), 8.46 (s, 1H), 14.46 (br. s., 1H). LC/MS (ESI+) m/z: 313 (M+H)+.

Reference： [1]Patent: US2012/71489,2012,A1 .Location in patent: Page/Page column 80-81

25
[ 4928-87-4 ]
[ 1361297-75-7 ]
5-((1R,5S)-9-(1H-1,2,4-triazole-3-carbonyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)-3-(6-phenylpyridin-3-yl)-8,9-dihydropyrazolo[1,5-a]pyrido[3,2-e]pyrimidin-6(7H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; for 0.5h;	5-(3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)-3-(6-phenylpyridin-3-yl)-8,9- dihydropyrazolotl,5-a]pyrido[3?2-e]pyrimidin-6(7H)-one (49.78 mg, 0.44 mmol) in DMF (2 mL) was treated with EDCI (129.47 mg, 0.678 mmol) and HOBt (45.6 mg, 0.339 mmol). Then substrate 5-(3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)-3-(6-phenylpyridin-3-yl)-8,9~dihydropyrazolo[l,5-a]pyrido[3,2-e]pyrimidin-6(7H)-one (122 mg, 0.21 rnmol) followed by DIEA (0.29 mL, 1.69 mmol) was added. After 30 min, the reaction mixture was treated with water (0.4 mL) and DMSO-MeCN (3:1, 3 mL). Pure compound 5-((lR,5S)-9-(lH- 1,2,4- triazole-3-carbonyl)-3-oxa-9-azabicyclo[3.3.1]nonan-7-yl)-3-(6-phenylpyridin-3-yl)-8,9- dihydropyrazolo[l,5-a]pyrido[352-e]pyrimidin-6(7H)-one was isolated by preparative HPLC. HPLC-MS 4.35 min (UV 254 r.m). Mass calculated for formula C30H27N9O3 561.2; observed MH+ (LCMS) 561.98 (m/z).

Reference： [1]Patent: WO2012/27234,2012,A1 .Location in patent: Page/Page column 78; 79

26
[ 4928-87-4 ]
[ 1361058-33-4 ]
[ 1361297-26-8 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 2h;	A mixture of 5-(8-azabicyclo[3.2.1]octan-3-yl)-3-(6-phenylpyridin-3-yl)-8,9- dihydropyrazolo[l,5-a]pyrido[3,2-e]pyrimidin-6(7H)-one (86 mg, 0.19 mmoL), 1H-1,2,4- triazole-3-carboxylic acid (25.9 mg, 0.23 mmoL), EDC (73 mg, 0.38mmoL), HOBt (51.6 mg, 0.38 mmoL) and DIEA (199 uL, 1.15 mmoL) in DMF (4 mL) was stirred at room temperature for 2h. Purification with prep-LC provided 5-(8-(4H-l,2,4-triazoIe-3-carbonyl)-8- azabicyclo[3.2.1 ]octan-3-yl)-3-(6-phenylpyridin-3-yl)-8,9-dihydropyrazolo[l ,5-a]pyrido[3,2- e]pyrimidin-6(7H)-one: LCMS tR = 2.33 Min (10 min run, UV 254nm)- Mass calculated for, M+ 545.2, observed LC/MS m/z 546.01 (M+H).

Reference： [1]Patent: WO2012/27234,2012,A1 .Location in patent: Page/Page column 45

27
[ 4928-87-4 ]
[ 1361297-52-0 ]
[ 1361297-27-9 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 2h;	A mixture of 5-(8-azabicyclo[3.2.1]octan-3-yl)-3-(6-phenylpyridin-3-yl)-8s9- di ydropyrazolo[l,5-a]pyrido[3,2-e]pyrirnidin-6(7H)-one (43.7 mg, 0.097 mmoL), Mn02 (42.2 mg, 0.48 mmoL) in DMF (3 mL) and CH2C12 (ImL)was heated at 120C overnight. The reaction mixture was cooled to room temperature and Mn02 was removed by filtration. 1H- l,2,4-triazole-3-carboxylic acid (12.2 mg, 0.11 mmoL), EDC (34.4 mg, 0.18mmoL), HOBt (24.3 mg, 0.18 mmoL) and DIEA (93.9 uL, 0.53 mmoL) was added and the mixture was stirred at room temperature for 2h. Purification with prep-LC provided 5-(8-(4H-l,2,4-triazole-3- carbonyl)-8-azabicyclo[ 3.2.1] octan-3 -yl)-3 -(6-phenylpyridin-3 -yl)pyrazolo [1,5 -a]pyrido [3 ,2- e]pyrimidin-6(9H)-one: LCMS tR = 2.18 Min (10 mm run, UV 254rim). Mass calculated for, M+ 543.2, observed LC/MS m/z 544.2 (M+H).

Reference： [1]Patent: WO2012/27234,2012,A1 .Location in patent: Page/Page column 45; 46

28
[ 4928-87-4 ]
[ 1361297-57-5 ]
[ 1361297-39-3 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 2h;	A mixture of 3-(6-phenylpyridin-3-yl)-5-(piperidin-4-yl)-8,9- dihydropyrazolo[l,5-a]pyrido[3,2-e]pyrimidin-6(7H)-one (70 mg, 0.17 mmoL), 1H- 1,2,4- triazole-3-carboxylic acid (20.5 mg, 0.18 mmoL), EDC (63 mg, 0.33mmoL), HOBt (44.6 mg, 0.33 mmoL) and DIEA (172.2 uL, 0.99 mmoL) in DMF (3 mL) was stirred at room temperature for 2h. Purification with prep-LC provided 5-(l-(4H-l ,2,4-triazole-3- carbonyl)piperidin-4-yl)-3~(6-phenylpyridin-3-yl)-8,9-dihydropyrazolo[l,5-a]pyrido[3s2- e]pyrimidin-6(7H)-one: LCMS tR = 3.15 Min (10 rain run, UV 254nm)- Mass calculated for, M+ 519.2, observed LC/MS m/z 519.97 (M+H).

Reference： [1]Patent: WO2012/27234,2012,A1 .Location in patent: Page/Page column 55; 56

29
[ 4928-87-4 ]
[ 1257106-16-3 ]
[ 1379619-12-1 ]

Yield	Reaction Conditions	Operation in experiment
		Example 1: N-[2-[[4-[(lR,3S)-3-[[( lR)-l-(4-Fluoro-3-methoxy-phenyl) ethyl]-amino]cyclopentyl]benzoyl]amino]ethyl]-lH-l,2,4-triazole-3- carboxamide (Compound 101)To a solution of Intermediate 4 (719 mg, 1.8 mmol) in dry DMF (12 mL) was added HOBt (276 mg, 2 mmol) and EDAC (517 mg, 2.7 mmol), and the mixture was stirred at rt for 4 hours. lH-l,2,4-triazole-3-carboxylic acid (200 mg, 1.8 mmol) was then added, and stirring was continued overnight at rt. The solvent was removed under reduced pressure and the crude purified by flash chromatography (30% MeOH/DCM), affording the title compound in 78% yield. *H NMR (300 MHz, DMSO) delta 8.70 (br m, IH), 8.48 (br m, IH), 8.41 (s, IH), 7.76 (d, J = 8.2 Hz, 2H), 7.31 (d, J = 8.2 Hz, 2H), 7.17 (dd, J = 8.6, 1.6 Hz, IH), 7.10 (dd, J = 11.5, 8.3 Hz, IH), 6.89 (ddd, J = 8.1, 4.4, 1.8 Hz, IH), 3.84 (s, 3H), 3.78 (q, J = 6.6 Hz, IH), 3.46 (br m, 4H), 3.04 - 2.85 (m, 2H), 2.15 - 1.54 (m, 6H), 1.43 - 1.19 (m, 4H).

Reference： [1]Patent: WO2012/69421,2012,A1 .Location in patent: Page/Page column 29-30

30
[ 4928-87-4 ]
5-(8-azabicyclo[3.2.1]octan-3-yl)-6-(methylsulfonyl)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-7-amine hydrochloride [ No CAS ]
[ 1319250-29-7 ]

Yield	Reaction Conditions	Operation in experiment
		Step D - Synthesis ((1R,3s,5S)-3-(7-amino-6-(methylsulfonyl)-3-(6-phenylpyridin-3- yl)pyrazolo[1,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octan-8-yl)(1H-1,2,4-triazol-3- yl)methanoneA mixture of 1 H-1 ,2,4-triazole-3-carboxylic acid (29.4 mg, 0.26 mmol), EDCI (76.7 mg, 0.4 mmol), and 1-hydroxybenzotriazole (27 mg, 0.2 mmol) in DMF (2 mL) was stirred at room temperature for 10 min. The 5-(8-azabicyclo[3.2.1]octan-3-yl)-6- (methylsulfonyl)-3-(6-phenylpyridin-3-yl)pyrazolo[1 ,5-a]pyrimidin-7-amine HCI (0.2 mmol) was added, followed by N,N-diisopropylethylamine (0.17 mL, 1 mmol). It was stirred further for 20 min at room temperature at which time LC/MS analysis confirmed full consumption of starting material. This crude compound was purification by HPLC to afford the desired title product.

Reference： [1]Patent: WO2011/90935,2011,A1 .Location in patent: Page/Page column 206

31
[ 4928-87-4 ]
[ 1319252-29-3 ]
((1R,3s,5S)-3-(7-amino-6-(methylsulfonyl)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octan-8-yl)(1H-1.2,4-triazol-3-yl)methanone hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Step 5. Synthesis of ((1R,3s,5S)-3-(7-amino-6-(methylsulfonyl)-3-(6-phenyl pyridin- 3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1 ]octan-8-yl) (1H-1,2, 4-triazol-3- yl) methanoneA mixture of 1 H-1 ,2,4-triazole-3-carboxylic acid (2.8 g, 24.4 mmol), EDCI (4.7 g, 24.4 mmol), and 1-hydroxybenzotriazole (2.2 g, 16.3 mmol) in DMF (100 mL) was stirred at room temperature for 10 min. To this mixture 5-((1 R,3s,5S)-8- azabicyclo[3.2.1]octan-3-yl)-6-(methylsulfonyl)-3-(6-phenylpyridin-3-yl)pyrazolo [1 ,5- a]pyrimidin-7-amine (12.2 g, 14.8 mmol) was added followed by N,N- diisopropylethylamine (12.9 mL, 73.9 mmol). It was stirred further for 20 min at room temperature, at which time LC/MS analysis confirmed full consumption of starting material. Solvent was removed in vacuo to complete dryness. To this crude was added water (200 mL) and solids were filtered and washed with additional water (200 mL). It was then washed with MeOH (125 mL), a 1 :1 mixture of ACN and water (200 mL), ACN (100 mL) and diethyl ether (100 mL) successively to afford ((1 R,3s,5S)-3- (7-amino-6-(methylsulfonyl)-3-(6-phenyl pyridin-3-yl)pyrazolo[1 ,5-a]pyrimidin-5-yl)-8- azabicyclo[3.2.1]octan-8-yl)(1 H-1 ,2,4-triazol-3-yl) methanone (7.5 g).; Step 6. Synthesis of ((1R,3s,5S)-3-(7-amino-6-(methylsulfonyl)-3-(6-phenyl pyridin- 3-yl) pyrazolo[1,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1 ]octan-8-yl)(1H-1,2, 4-triazol-3- yl) methanone hydrochlorideTo a suspension of ((1 R,3s,5S)-3-(7-amino-6-(methylsulfonyl)-3-(6-phenyl pyridin-3-yl) pyrazolo[1 ,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octan-8-yl)(1 H-1 ,2,4- triazol-3-yl) methanone (8g, 14.1 mmol) in DCM (350 mL) and MeOH (100 mL) was added 4M HCI in 1 ,4-dioxane (14.1 mL, 56.2 mmol). It was stirred further for 10 min at room temperature during which time solution became clear. Solvent was removed in vacuo until solids were precipitate out. To this crude was added diethyl ether (200 mL) and solids were filtered and washed with additional diethyl ether (800 mL).Solids were redissolved in a 1 :1 mixture of ACN and water and lyophilized to get the desired ((1 R,3s,5S)-3-(7-amino-6-(methyl sulfonyl)-3-(6-phenylpyridin-3- yl)pyrazolo[1 ,5-a] pyrimidin-5-yl)-8-azabicyclo [3.2.1]octan-8-yl)(1 H-1 ,2,4-triazol-3- yl)methanone as an HCI salt (8.5 g).

Reference： [1]Patent: WO2011/90935,2011,A1 .Location in patent: Page/Page column 211-212

32
[ 4928-87-4 ]
[ 1319248-56-0 ]
1-(5-((1R,3S,5S)-8-(4H-1,2,4-triazole-3-carbonyl)-8-azabicyclo[3.2.1]octan-3-yl)-7-amino-3-(6-(1-methyl-1H-pyrazol-3-yl)pyridin-yl)pyrazolo[1,5-a]pyrimidin-6-yl)ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 1h;	Step 5: Preparation of 1-(5-((1 R,3s,5S)-8-(4H-1 ,2,4-triazole-3-carbonyl)-8- azabicyclo[3.2.1]octan-3-yl)-7-amino-3-(6-(1 -methyl-1 H-pyrazol-3-yl)pyridin- yl)pyrazolo[1 ,5-a]pyrimidin-6-yl)ethanone 1 H-1 ,2,4-triazole-3-carboxylic acid (58.0 mg, 0.51 mmol), EDC (133.7 mg, 0.70 mmol), HOBt (94.5 mg, 0.70 mmol) and DIEA (730 uL, 4.20 mmol) were added to a mixture of 1-(7-amino-5-((1 R,3s,5S)-8-azabicyclo[3.2.1]octan-3-yl)-3-(6-(1- methyl-1 H-pyrazol-3-yl)pyridin-3-yl)pyrazolo[1 ,5-a]pyrimidin-6-yl)ethanone (207.7 mg, 0.47 mmol) in DMF (5 mL) and the mixture was stirred at room temperature for 1 h. Purification with prep-LC provided 1-(5-((1 R,3s,5S)-8-(4H-1 ,2,4-triazole-3- carbonyl)-8-azabicyclo[3.2.1]octan-3-yl)-7-amino-3-(6-(1 -methyl-1 H-pyrazol-3- yl)pyridin-3-yl)pyrazolo[1 ,5-a]pyrimidin-6-yl)ethanone.

Reference： [1]Patent: WO2011/90935,2011,A1 .Location in patent: Page/Page column 194

33
[ 4928-87-4 ]
[ 1319256-08-0 ]
[ 1319252-65-7 ]

Yield	Reaction Conditions	Operation in experiment
		Step 3 Synthesis of 5-((1 R, 3s, 5S)-8-(1 H-1,2, 4-triazole-3-carbonyl)-8-azabicyclo[3.2.1 ]octan- 3-yl)-7-amino-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidine-6-carbonitriA mixture of 1 H-1 ,2,4-triazole-3-carboxylic acid (29.4 mg, 0.26 mmol), EDCI (76.7mg, 0.4 mmol), and 1-hydroxybenzotriazole (27 mg, 0.2 mmol) in DMF (2 mL) was stirred at room temperature for 10 min. Substrate 7-amino-5-((1 R,3s,5S)-8- azabicyclo[3.2.1]octan-3-yl)-3-(6-phenylpyridin-3-yl)pyrazolo[1 ,5-a]pyrimidine-6- carbonitrile (0.2 mmol) was added followed by W,W-diisopropylethylamine (0.17ml, 1 mmol). It was stirred further for 20min at room temperature at which time LC/MS analysis confirmed full consumption of starting material. This crude compound was submitted to the analytical group for purification to afford the desired product.

Reference： [1]Patent: WO2011/90935,2011,A1 .Location in patent: Page/Page column 295-296

34
[ 4928-87-4 ]
[ 1319252-70-4 ]
[ 1319252-71-5 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃;	Example 5-5Preparation of ((1R, 3s, 5S)-3-(7-amino-6-isopropyl-3-( 6-phenylpyridin-3- yl)pyrazolo[1,5-a]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octan-8-yl)(4H-1,2,4-triazol-3- yl)methanoneA mixture of 5-((1 R,3s,5S)-8-azabicyclo[3.2.1]octan-3-yl)-6-isopropyl-3-(6- phenylpyridin-3-yl)pyrazolo[1 ,5-a]pyrimidin-7-amine (30 mg, 0.068 mmol), 41-1-1 ,2,4- triazole-3-carboxylic acid (10.1 mg, 0.085 mmoL), EDC (26.0 mg, 0.14 mmoL), HOBt (18.4 mg, 0.14 mmoL) and DIEA (70.9 ul, 0.41 mmoL) in DMF (2 mL) was stirred at room temperature. Purification with prep-LC provided ((1 R,3s,5S)-3-(7-amino-6- isopropyl-3-(6-phenylpyridin-3-yl)pyrazolo[1 ,5-a]pyrimidin-5-yl)-8- azabicyclo[3.2.1]octan-8-yl)(4H-1 ,2,4-triazol-3-yl)methanone, LCMS tR = 2.25 Min (10 min run, UV254nm). Mass calculated for, M+ 533.2, observed LC/MS m/z 533.99 (M+H).

Reference： [1]Patent: WO2011/90935,2011,A1 .Location in patent: Page/Page column 300-301

35
[ 4928-87-4 ]
1-(7-amino-5-((1R,3s,5S)-8-azabicyclo[3.2.1]octan-3-yl)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-6-yl)ethanone hydrochloride [ No CAS ]
[ 1319248-45-7 ]

Yield	Reaction Conditions	Operation in experiment
		Step 14 Synthesis of 1 -(5-((1 R, 3s, 5S)-8-(4H-1 ,2, 4-triazole-3-carbonyl)-8- azabicyclo[3.2.1 ]octan-3-yl)-7-amino-3-(6-phenylpyridin-3-yl)pyrazolo[1,5- a]pyrimidin-6-yl)ethanoneA mixture of 1 H-1 ,2,4-triazole-3-carboxylic acid (29.4 mg, 0.26 mmol), EDCI (76.7 mg, 0.4mmol), and 1-hydroxybenzotriazole (27 mg, 0.2 mmol) in DMF (2 ml) was stirred at room temperature for 10min. Compound 1-(7-amino-5-((1 R,3s,5S)-8- azabicyclo[3.2.1]octan-3-yl)-3-(6-phenylpyridin-3-yl)pyrazolo[1 ,5-a]pyrimidin-6- yl)ethanone hydrochloride (0.2 mmol) was added followed by N,N- diisopropylethylamine (0.17 ml, 1 mmol). It was stirred further for 20min at room temperature at which time LC/MS analysis confirmed full consumption of starting material. This crude compound was submitted to the analytical group for purification to afford the desired product. LC/MS RT = 2.42 min. Mass calculated for M+H 534.2, observed 534.2.

Reference： [1]Patent: WO2011/90935,2011,A1 .Location in patent: Page/Page column 125-126

36
[ 4928-87-4 ]
[ 1319255-56-5 ]
[ 1319255-57-6 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 1h;	Example 1-30 Preparation of provided 5-(5-((1R, 3s, 5S)-8-(4H-1,2, 4-triazole-3-carbonyl)-8- azabicyclo[3.2.1 ]octan-3-yl)-6-acetyl-7-aminopyrazolo[1,5-a]pyrimidin-3-yl)picolinic acidA mixture of methyl 5-(6-acetyl-7-amino-5-((1 R,3s,5S)-8- azabicyclo[3.2.1]octan-3-yl)pyrazolo[1 ,5-a]pyrimidin-3-yl)picolinate (99.5 mg, 0.237 mmol), 4H-1 ,2,4-triazole-3-carboxylic acid (32.2 mg, 0.285 mmoL), EDC (90.7 mg, 0.475 mmol), HOBt (64.1 mg, 0.475 mmol) and DIEA (247.6 ul, 1.42 mmol) in DMF (5 mL) was stirred at room temperature for 1 h. Concentration provided crude methyl 5-(5-((1 R,3s,5S)-8-(4H-1 ,2,4-triazole-3-carbonyl)-8-azabicyclo[3.2.1]octan-3-yl)-6- acetyl-7-aminopyrazolo[1 ,5-a]pyrimidin-3-yl)picolinate. MeOH (2 ml), THF (1 ml) and 1 N NaOH (2 ml) were added and the mixture was stirred at 50C until LCMS indicated complete conversion. Concentration and Purification with prep-LC provided5- (5-((1 R,3s,5S)-8-(4H-1 ,2,4-triazole-3-carbonyl)-8-azabicyclo[3.2.1]octan-3-yl)-6- acetyl-7-aminopyrazolo[1 ,5-a]pyrimidin-3-yl)picolinic acid, LCMS tR = 1.85 Min (10 min run, UV254nm). Mass calculated for, M+ 501.1 , observed LC/MS m/z 501.96 (M+H).

Reference： [1]Patent: WO2011/90935,2011,A1 .Location in patent: Page/Page column 144-145

37
[ 4928-87-4 ]
6-((1R,3s,5S)-8-azabicyclo[3.2.1]octan-3-yl)-3-(6-phenylpyridin-3-yl)imidazo[1,2-a]pyrazin-8-amine [ No CAS ]
[ 1421425-95-7 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 1h;	Step 7: Preparation of ((lR,3s,5S)-3-(8-amino-3-(6-phenylpyridin-3-yl)imidazo[l,2-a]pyrazin- 6-yl)-8-azabicyclo[3.2.1]octan-8-yl)(4H-l ,2,4-triazol-3-yl)methanone A mixture of crude 6-((lR,3s,5S)-8-azabicyclo[3.2.1]octan-3-yl)-3-(6-phenylpyridin- 3-yl)imidazo[l,2-a]pyrazin-8-amine from step 7, lH-l ,2,4-triazole-3-carboxylic acid (33.0 mg, 0.29 mmol), EDCI (92.9 mg, 0.49 mmol), 1-hydroxybenzotriazole (65.6 mg, 0.49 mmol) and DIEA (253 ul, 1.46 mmol) in DMF (5 mL) was stirred at room temperature for lh.Purification with prep-LC and conversion to HCl salt provided ((lR,3s,5S)-3-(8-amino-3-(6- phenylpyridin-3-yl)imidazo[l,2-a]pyrazin-6-yl)-8-azabicyclo[3.2.1]octan-8-yl)(4H-l ,2,4- triazol-3-yl)methanone as HCl salt: LCMS tR = 2.25 Min (10 min run, UV254nm). Mass calculated for, M+ 491.2, observed m/z 492.3 (M+H).

Reference： [1]Patent: WO2013/16160,2013,A1 .Location in patent: Page/Page column 57

38
[ 4928-87-4 ]
[ 1421271-44-4 ]
[ 1421271-37-5 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 20℃; for 1h;	A mixture of l-(7-Amino-5-(-8-azabicyclo[3.2.1]octan-3-yl)-3-(6-phenylpyridin-3- yl)pyrazolo[l,5-a]pyrimidin-6-yl)ethanone (131.4mg, 0.30 mmol), N2H4.H2O (150 ul, 3.0 mmol) in NMP (10 ml) was heated first at 100C for 30 min and then at 200C for 60 min under microwave condition. The mixture was put on rotovap and concentrated at 60C for 2h to remove excess N2H4.H20. lH-l,2,4-triazole-3-carboxylic acid (101.7 mg, 0.90 mmol), EDC (229 mg, 1.20 mmol), HOBt (121.5 mg, 0.90 mmol) and DIEA (521.6 uL, 3.0 mmol) were then added and the mixture was stirred at room temperature for lh. Purification with prep-LC pro ided (( 1 R,3 s,5 S)-3 -(3 -methyl-6-(6-phenylpyridin-3 -yl)- 1 H-dipyrazolo [1,5- a:4',3'-e]pyrimidin-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)(4H-l,2,4-triazol-3-yl)methanone.

Reference： [1]Patent: WO2013/16164,2013,A1 .Location in patent: Page/Page column 61; 62

39
[ 4928-87-4 ]
[ 1421271-46-6 ]
[ 1421271-38-6 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 2h;	A mixture of 5-((lR,3s,5S)-8-azabicyclo[3.2.1]octan-3-yl)-3-(6-phenylpyridin-3-yl)- 8H-pyrazolo[l,5-a]pyrrolo[3,2-e]pyrimidine (0.19 mmol), lH-l,2,4-triazole-3-carboxylic acid (21.7mg, 0.19 mmol), EDC (58.6 mg, OJ lmmol), HOBt (25.9 mg, 0.19 mmol) and DIEA (200 uL, 1.15 mmol) in DMF (5 mL) was stirred at room temperature for 2 h. Purification with prep-LC provided ((lR,3s,5S)-3-(3-(6-phenylpyridin-3-yl)-8H-pyrazolo[l,5- a]pyrrolo[3,2-e]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octan-8-yl)(4H-l,2,4-triazol-3- yl)mefhanone.

Reference： [1]Patent: WO2013/16164,2013,A1 .Location in patent: Page/Page column 63; 64

40
[ 4928-87-4 ]
[ 1421271-48-8 ]
[ 1421271-39-7 ]

Yield	Reaction Conditions	Operation in experiment
		A mixture of lH-l,2,4-triazole-3-carboxylic acid (22.6 mg, 0.2 mmol), EDCI (76.7 mg, 0.4 mmol), and 1-hydroxybenzotriazole (27 mg, 0.2 mmol) in DMF (2 mL) was stirred at room temperature for lOmin. Crude 2-(5-(5-((lR,3s,5S)-8-azabicyclo[3.2.1]octan-3-yl)-8H- pyrazolo[l ,5-a]pyrrolo[3,2-e]pyrimidin-3-yl)pyridin-2-yl)propan-2-ol from step 6 (0.25 mmol) was added followed by N,N-diisopropylethylamine (0.18 mL, 1 mmol). It was stirred further for 20 minutes at room temperature at which time LC/MS analysis confirmed full consumption of starting material. Pure compound ((lR,3s,5S)-3-(3-(6-(2-hydroxypropan-2- yl)pyridin-3-yl)-8H-pyrazolo[l,5-a]pyrrolo[3,2-e]pyrimidin-5-yl)-8-azabicyclo[3.2.1]octan-8- yl)(lH-l ,2,4-triazol-3-yl)methanone was isolated by preparative HPLC.

Reference： [1]Patent: WO2013/16164,2013,A1 .Location in patent: Page/Page column 68; 69

41
[ 4928-87-4 ]
chloroanhydride of 1H-1,2,4-triazole-3-carboxylic acid hydrochloride [ No CAS ]

Reference： [1]Russian Journal of Bioorganic Chemistry,2013,vol. 39,p. 53 - 71
Bioorganicheskaya Khimiya,2013,vol. 39,p. 61 - 80,20

42
[ 4928-87-4 ]
C₆H₅N₅O [ No CAS ]

Reference： [1]Russian Journal of Bioorganic Chemistry,2013,vol. 39,p. 53 - 71
Bioorganicheskaya Khimiya,2013,vol. 39,p. 61 - 80,20

43
[ 4928-87-4 ]
[ 3282-30-2 ]
C₁₃H₁₉N₃O₄ [ No CAS ]

Reference： [1]Russian Journal of Bioorganic Chemistry,2013,vol. 39,p. 53 - 71
Bioorganicheskaya Khimiya,2013,vol. 39,p. 61 - 80,20

44
[ 4928-87-4 ]
lead(II) nitrate [ No CAS ]
[ 7681-11-0 ]
[ 1429689-06-4 ]

Yield	Reaction Conditions	Operation in experiment
63%	In water; at 60℃; for 240h;	Compound 1 was prepared using the branched tube method [11]: 1H-<strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong> (0.117 g, 1 mmol), potassium iodide (0.166 g, 1 mmol) and lead(II) nitrate (0.331 g, 1 mmol) were placed in the arm to be heated. Water was carefully added to fill both arms, and then the arm to be heated was placed in a bath at 60 C. After 10 days, yellow crystals were deposited in the cooler arm which were filtered off, washed with water and air dried. (0.28 g, yield 63%), m.p. > 300 C. Anal. Calc. for C3H2IN3O2Pb: C, 8.07; H, 0.45; N, 9.41. Found: C, 8.15; H, 0.43; N, 9.63%. IR (cm-1) selected bands: 810(m), 981(m), 1280(m), 1453(vs), 1622(vs), 3102(br) and 3444(br).

Reference： [1]Inorganica Chimica Acta,2013,vol. 398,p. 151 - 157

45
[ 4928-87-4 ]
lead(II) nitrate [ No CAS ]
[ 1338359-40-2 ]

Yield	Reaction Conditions	Operation in experiment
54%	With potassium bromide; at 60℃; for 72h;	Single crystals of 1 were prepared by a branched tube method [13], 1H-<strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong> (0.117 g, 1 mmol), lead(II) nitrate (0.331 g, 1 mmol) and potassium bromide (0.119 g, 1 mmol) were placed in the bottom main of a branched tube. Water was carefully added to fill both arms, and then the arm to be heated was placed in oil bath at 60 C. After 3 days, colorless crystals were deposited in the cooler arm which were filtered off, washed with water and air dried. (0.225 g, yield 54%), m.p. ?195 C. (Found C 8.55, H 0.99, N 10.43%. calculated for C3H4BrN3O3Pb; C 8.63, H 0.96, N 10.07%). IR (cm-1) selected bands: 464 (s), 651 (s), 1100 (s), 1303 (m), 1370 (m), 1457 (vs), 1606 (s) and 3370 (br).

Reference： [1]Ultrasonics Sonochemistry,2013,vol. 20,p. 1254 - 1260

46
[ 4928-87-4 ]
lead(II) nitrate [ No CAS ]
[ 1338359-40-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium bromide; sodium hydroxide; In water;Sonication; Irradiation; Green chemistry;	To prepare the nanoparticles of 1, 50ml solution of lead(II) nitrate (0.01 M) in water was positioned in a high-density ultrasonic probe, operating at 40 kHz with a maximum power output of 305 W. Into this aqueous solution a 50 ml solution of the ligand 1H-<strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong> (0.01 M) and sodium hydroxide (0.01 M) and potassium bromide (0.01 M) were added dropwise. The obtained precipitates were filtered off, washed with water and then dried in air. m.p.?180 C. (Found C 8.61, H 0.89, N 10.12%). IR (cm-1) selected bands: 466 (s), 661 (s), 1106 (s), 1309 (m), 1373 (m), 1465 (vs), 1610 (s) and 3373 (br).

Reference： [1]Ultrasonics Sonochemistry,2013,vol. 20,p. 1254 - 1260

47
[ 4928-87-4 ]
manganese(II) chloride tetrahydrate [ No CAS ]
[ 7732-18-5 ]
C₆H₈MnN₆O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide;Sonication;	To prepare nano-sized [Mn(L)2(H2O)2] (1), 50ml solution of manganese(II) chloride tetrahydrate (0.1molL-1) in water was positioned in a high-density ultrasonic probe, operating at 40kHz with a maximum power output of 305W. Into this solution water a 50ml solution of the ligand 1H-<strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong> (0.1molL-1) and potassium hydroxide (0.01molL-1) were added dropwise. The obtained precipitates were filtered off, washed with water and then dried in air. m.p.>300C.

Reference： [1]Ultrasonics Sonochemistry,2014,vol. 21,p. 253 - 261

48
[ 4928-87-4 ]
manganese(II) chloride tetrahydrate [ No CAS ]
[ 7732-18-5 ]
[Mn(1H-1,2,4-triazole-3-carboxylate)₂(H₂O)₂] [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51.3%	With potassium hydroxide; at 60℃; for 240h;	To isolate single crystals of [Mn(L)2(H2O)2] (1), 1H-<strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong> (0.117 g, 1 mmol), potassium hydroxide (0.04 g, 1 mmol) and manganese(II) chloride tetrahydrate (0.098 g, 0.5 mmol) were placed in the main arm of a branched tube to be heated. Water was carefully added to fill both arms, and then the arm to be heated was placed in a bath at 60 C. After 10 days, colorless crystals were deposited in the cooler arm which were filtered off, washed with water and air dried. (0.161 g, yield 51.3%), m.p. > 300 C.

Reference： [1]Ultrasonics Sonochemistry,2014,vol. 21,p. 253 - 261

49
[ 4928-87-4 ]
lead(II) nitrate [ No CAS ]
[ 7558-02-3 ]
[ 1338359-40-2 ]

Yield	Reaction Conditions	Operation in experiment
54%	at 60℃; for 168h;	Single crystals of 1 were prepared by a branched tube method [34], 1H-<strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong> (0.117 g, 1 mmol), lead(II) nitrate (0.331 g, 1 mmol) and potassium bromide (0.119 g, 1 mmol) were placed in the bottom main of a branched tube. Water was carefully added to fill both arms, and then the arm to be heated was placed in oil bath at 60 C. After 7 days, colorless crystals were deposited in the cooler arm which were filtered off, washed with water and air dried. (0.225 g, yield 54%),

Reference： [1]Inorganica Chimica Acta,2013,vol. 405,p. 203 - 208

50
[ 4928-87-4 ]
lead(II) nitrate [ No CAS ]
[ 7558-02-3 ]
[ 1338359-40-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water;Sonication;	General procedure: To prepare the nanoparticles of 1, 50 ml solution of lead(II) nitrate(0.01 M) in water was positioned in a high-density ultrasonic probe, operating at 50 Hz with a maximum power output of 305 W. Into this aqueous solution a 50 ml solution of the ligand 1H-<strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong> (0.01 M) and sodium hydroxide (0.01 M) and potassium bromide (0.01 M) were added dropwise.The obtained precipitates were filtered off, washed withwater and then dried in air.

Reference： [1]Inorganica Chimica Acta,2013,vol. 405,p. 203 - 208

51
[ 4928-87-4 ]
lead(II) nitrate [ No CAS ]
[ 333-20-0 ]
C₃H₂N₃O₂^(1-)*Pb⁽²⁺⁾*CNS^(1-)*H₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water;Sonication;	General procedure: To prepare the nanoparticles of 1, 50 ml solution of lead(II) nitrate(0.01 M) in water was positioned in a high-density ultrasonic probe, operating at 50 Hz with a maximum power output of 305 W. Into this aqueous solution a 50 ml solution of the ligand 1H-<strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong> (0.01 M) and sodium hydroxide (0.01 M) and potassium bromide (0.01 M) were added dropwise.The obtained precipitates were filtered off, washed withwater and then dried in air.

Reference： [1]Inorganica Chimica Acta,2013,vol. 405,p. 203 - 208

52
[ 4928-87-4 ]
lead(II) nitrate [ No CAS ]
[ 333-20-0 ]
C₃H₂N₃O₂^(1-)*Pb⁽²⁺⁾*CNS^(1-)*H₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	at 60℃; for 168h;	General procedure: Single crystals of 1 were prepared by a branched tube method [34], 1H-<strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong> (0.117 g, 1 mmol), lead(II) nitrate (0.331 g, 1 mmol) and potassium bromide (0.119 g, 1 mmol) were placed in the bottom main of a branched tube. Water was carefully added to fill both arms, and then the arm to be heated was placed in oil bath at 60 C. After 7 days, colorless crystals were deposited in the cooler arm which were filtered off, washed with water and air dried. (0.225 g, yield 54%),

Reference： [1]Inorganica Chimica Acta,2013,vol. 405,p. 203 - 208

53
[ 4928-87-4 ]
lead(II) nitrate [ No CAS ]
potassium chloride [ No CAS ]
[Pb(3-carboxylic acid-4H-1,2,4-triazole(-H))(μ2-Cl)(H2O)](n) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	at 60℃; for 168h;	General procedure: Single crystals of 1 were prepared by a branched tube method [34], 1H-<strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong> (0.117 g, 1 mmol), lead(II) nitrate (0.331 g, 1 mmol) and potassium bromide (0.119 g, 1 mmol) were placed in the bottom main of a branched tube. Water was carefully added to fill both arms, and then the arm to be heated was placed in oil bath at 60 C. After 7 days, colorless crystals were deposited in the cooler arm which were filtered off, washed with water and air dried. (0.225 g, yield 54%),

Reference： [1]Inorganica Chimica Acta,2013,vol. 405,p. 203 - 208

54
[ 4928-87-4 ]
[ 1416231-32-7 ]
[ 1416233-14-1 ]

Yield	Reaction Conditions	Operation in experiment
35%		<strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong> (116 mg, 1.02 mmol) was dissolved in methylene chloride (20 ml) and DMF (5 ml), reacted with EDCI (196 mg, 1.02 mmol) and HOBt (138 mg, 1.02 mmol) for 20 min, and then stirred together with 4b-amino-9b-hydroxy-7-isopropyl-4b,9b-dihydro-5-oxa-indeno[2,1-a]-inden-10-one (300 mg, 1.02 mmol) overnight at room temperature. After extraction with methylene chloride and water, the organic layer was dried over MgSO4 and concentrated in a vacuum. Purification by column chromatography (10% methanol in methylene chloride) afforded the title compound as a white solid. (141 mg, 35%). [0812] 1H-NMR (300 MHz, CD3OD) delta 1.17 (d, J=6.9 Hz, 6H, CH3), 2.85 (sep, J=6.9 Hz, 1H, CH), 6.68 (s, 1H, ArH), 6.90 (d, J=8.0 Hz, 1H, ArH), 7.45 (d, J=7.9 Hz, 1H, ArH), 7.607.97 (m, 4H, ArH), 8.40 (s, 1H, ArH).

Reference： [1]Patent: US2014/114068,2014,A1 .Location in patent: Paragraph 0811-0812

55
[ 4928-87-4 ]
[ 712-76-5 ]
N-[(1,1'-biphenyl)-4-ylmethyl]-1H-1,2,4-triazole-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; 6-chloro-1-hydroxybenzotriazole; In dichloromethane; N,N-dimethyl-formamide; at 20℃; for 12h;Inert atmosphere;	General procedure: To a 0.2 M solution of amine (0.1-10 mmol, 1 equiv) and carboxylic acid (1 equiv) in DCM was added Cl-HOBt (1.05 equiv)and Et3N (1.3 equiv) followed by EDC-HCl (1.2 equiv). The mixture was stirred at rt for 12 h. The crude mixture was diluted with DCM and washed once with 1 M HCl, once with satd NaHCO3 and once with brine. The DCM solution was evaporated to afford the product with >90% purity. The product was recrystallized from Et2O/hexane or purified by silica gel chromatography if necessary. Yields were typically >75%.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 3971 - 3981

56
[ 4928-87-4 ]
(3aR,5R,6aS)-5-(2-(trifluoromethyl)phenyl)octahydrocyclopenta[c]pyrrole hydrochloride [ No CAS ]
(1H-1,2,4-triazol-3-yl)((3aR,5R,6aS)-5-(2-(trifluoromethyl)phenyl)hexahydrocyclopenta[c]pyrrole-2(1H)-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine; In N,N-dimethyl-formamide; at 20℃;	General procedure: General Procedure (GP-Al) for carboxamide formation: A mixture of amine I (1 equiv) , desired carboxylic acid (1 equiv) , triethylamine (Et3N) (3 equiv) , and 2- (lfl-benzotriazole-l-yl) -1 , 1 , 3 , 3- tetramethyluronium hexafluoro-phosphate (HBTU) (1.5 equiv) in DMF (0.25 M) was stirred at room temperature until the reaction was complete by TLC or LC-MS. The mixture was diluted with 0 and extracted with EtOAc. The combined organic extracts were washed with H2O , brine, dried over Na2S0< , filtered, and concentrated under reduced pressure. The resulting residue was purified by either normal phase silica gel column chromatography (typical eluents included either a mixture of or hexanes and EtOAc or a mixture of CH2CI2 and a 90:9:1 mixture of CH2CI2/CHjOH/concentrated NH4OH} or C- 18 reversed phase column chromatography (typical eluents included CCN and H20) to afford the desired carboxamide XX. The product structure was verified by 1H NMR and by mass analysis. Example 2: (lH-1, 2, 4-Triazol-3-yl) ( ( 3a, 5R, 6aS) -5- (2- (trifluoromethyl)phenyl>hexahydrocyclopenta fc]pyrrol-2 (IH) -yl) methanone 18) Step A: Following general procedure GP-A1 , (3aR, 5S, 6aS) -5- (2- (trifluoromethyl) henyl) octahydrocyclopenta [c] yrrole hydrochloride and IH-l , 2 , 4-triazole-3-carboxylic acid were converted to (1H-1,2,4- triazol-3-yl) ( (3ai, SR, 6&S) -5- (2- (trifluoromethyl(phenyl) hexahydrocyclopenta[c]pyrrol-2 (IH) -yl)methanone as a white solid (0.071 g, 52%): NMR (500 MHz, CDC13) delta 12.7.1 (bs, IH) , 8.12 (bs, IH) , 7.67 (m, IH), 7.49 (m, 2H) , 7.26 (m, IH) , 4.43 (m, 2H) , 3.93 (m, 2H) , 3.53 (m, IH) , 3.08-2.81 (m, 2H) , 2.42 (m, 2H) , 1.65 (m, 2H) ; ESI MS m/z 351 [M + H]*.

Reference： [1]Patent: WO2014/152018,2014,A1 .Location in patent: Page/Page column 73-74; 94

57
[ 4928-87-4 ]
(3aR,6aS)-5-(2-(trifluoromethyl)phenyl)octahydrocyclopenta[c]pyrrole hydrochloride [ No CAS ]
3-[(3aR,6aS)-5-[2-(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrol-2-yl]carbonyl}-1H-1,2,4-triazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine; In N,N-dimethyl-formamide; at 20℃;	General procedure: A mixture of amine I (1 equiv), desired carboxylic acid (1 equiv), triethylamine (Et3N) (3 equiv), and 2-(lH-benzotriazo1elyl),l,3,3tetranethyluronium hexafluoro-phosphate (HBTU) (1.5 equiv) in DMF (0.25 H) was stirred at room temperature until the reaction was complete by TLC or LCMS. The mixture was diluted with H,O andextracted with EtOAc. The combined organic extracts were washed with H,O, brine, dried over Ha,804, filtered, and concentrated under reduced pressure. The resulting residue was purified by either normal phase silica gel column chromatography (typical eluents included either a mixture of or hexanes and EtOAc or a mixture ofCH,Cl, and a 90:9:1 mixture of CH,Cl,/CH,OH/concentrated NH,OH) or C-18 reversed phase column chromatography (typical eluents included CH,CN and H,O( to afford the desired carboxamide It. The product structure was verified by ?H NMR and by mass analysis.

Reference： [1]Patent: WO2014/151936,2014,A1 .Location in patent: Page/Page column 72; 73; 94

58
[ 4928-87-4 ]
(S)-4-(aminomethyl)-N-(4-chloro-2-(2-methyl-4-(3,3,3-trifluoropropyl)piperazin-1-yl)phenyl)-2,3-difluorobenzamide [ No CAS ]
(S)-N-(4-((4-chloro-2-(2-methyl-4-(3,3,3-trifluoropropyl)piperazin-1-yl)phenyl)carbamoyl)-2,3-difluorobenzyl)-1H-1,2,4-triazole-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
34.6%	With N-ethyl-N,N-diisopropylamine; HATU; In acetonitrile; at 20℃; for 12h;	A mixture of (S)-4-(aminomethyl)-N-(4-chloro-2-(2-methyl-4-(3,3,3-trifluoropropyl)piperazin- l-yl)phenyl)-2,3-difluorobenzamide (0.08 g, 0.16 mmol), l/ -l ,2,4-triazole-3-carboxylic acid (0.10 g, 0.88 mmol) and DIPEA (0.2 mL, 1.1 mmol) in CH3CN (2.5 mL) was stirred at room temperature for 10 min, then HATU (0.08 g, 0.21 mmol) was added. And then the mixture was stirred at room temperature for 12 h and was purified by HPLC to give the title compound (0.033 g, 34.6%). LC/MS m/z = 586.1 [M+l]+.

Reference： [1]Patent: WO2014/182688,2014,A1 .Location in patent: Page/Page column 113

59
[ 4928-87-4 ]
[ 95-64-7 ]
N-(3,4-dimethylphenyl)-1H-1,2,4-triazole-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 16h;Inert atmosphere;	General procedure: The tail group amines Ar-NH2 (Ar a-d) (19.5 mmol,1.1 equiv) were added to a stirring solution of <strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong> 12 (2.00 g, 17.7 mmol, 1.0 equiv) in dry DMF(30 mL) at room temperature. After 5 min, TBTU (6.0 g, 18.6 mmol,1.0 equiv) and DIPEA (11.0 mL, 61.9 mmol, 3.5 equiv) were added insequence. The resulting solution was stirred at room temperaturefor 16 h. After completion of the reaction, as indicated by TLC, DMFwas removed by rotary evaporation at 30 torr and 70 C. The crudematerial was purified by methods described in each individualentry.

Reference： [1]European Journal of Medicinal Chemistry,2020,vol. 189
[2]ACS Combinatorial Science,2014,vol. 16,p. 485 - 493

60
[ 4928-87-4 ]
[ 1361189-49-2 ]
[ 1361187-29-2 ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 1669 - 1690

61
[ 4928-87-4 ]
C₁₂H₁₇N₃O₅*C₂HF₃O₂ [ No CAS ]
N-(3-((1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-ylamino)-3-oxopropyl)-1H-1,2,4-triazole-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%		To an ice-cold solution of the above obtained salt (0.25 g,0.63 mmol) in DMF (0.8 mL), iPr2NEt (0.33 mL, 1.89 mmol) wasadded. The reaction mixture was stirred at 0 C for 10 min and thenTCA (0.064 g, 0.57 mmol) and PyBrOP (0.32 g, 0.68 mmol) wereadded sequentially. The mixture was stirred at ambient temperaturefor 1 h and then it was diluted with EtOAc. The organic phasewas washed once with a 5% aq solution of NaHCO3 and thrice withH2O, dried over Na2SO4 and evaporated to dryness. Compound 9was purified with FCC. Yield: 0.16 g (75%); white foam; Rf(CHCl3/MeOH 9:1): 0.12; IR (KBr, cm1): 3117, 3041, 2931, 1648,1540, 1060; MS (ESI, 30 eV): m/z 417.45 [M+K], 401.24 [M+Na],379.28 [M+H]; HRMS (m/z): [M+H]+ calcd for C15H19N6O6,379.1366. Found: 379.1398; 1H NMR (d6-DMSO): d 9.27(t, J = 5.2 Hz, 1H), 8.30 (s, 1H), 8.14 (d, J = 8.8 Hz, 2H), 7.68 (d,J = 9.2 Hz, 1H), 7.57 (d, J = 8.8 Hz, 2H), 5.82 (br s, 1H), 5.00 (1H,unresolved d), 4.84 (br s, 1H), 4.02-3.94 (m, 1H), 3.54 (unresolveddd, 1H), 3.29 (dd, J = 6.0 and 10.4 Hz, 1H), 3.20 (q, J = 6.8 Hz, 2H),2.36-2.20 (m, 2H); 13C NMR (d6-DMSO): d 170.1 (two C), 156.9,156.3, 152.4, 146.8, 127.8 (two C), 123.2 (two C), 69.8, 60.9, 56.4,36.4, 34.3.

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 3163 - 3174

62
[ 4928-87-4 ]
[ 119-62-0 ]
N-((1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl)-1H-1,2,4-triazole-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With N-ethyl-N,N-diisopropylamine; bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate; In N,N-dimethyl-formamide; at 25℃; for 2h;Cooling with ice;	To an ice-cold solution of CLB (0.21 g, 1.0 mmol) in DMF (1.2 mL), TCA (0.14 g, 1.2 mmol), iPr2NEt (0.52 mL, 3.0 mmol) and bromotripyrrolidinophosphonium hexafluorophosphate (PyBrOP) (0.67 g, 1.44 mmol) were added sequentially. The reaction mixture was stirred at ambient temperature for 2 h and then diluted with EtOAc. The organic phase was washed twice with a 5% aq solution of NaHCO3 and thrice with H2O, dried over Na2SO4 and evaporated to dryness to afford an oily residue. Conjugate 8 was purified with FCC. Yield: 0.25 g (80%); white foam; Rf (CHCl3/MeOH 8:2): 0.26; IR (KBr, cm-1): 3122, 3028, 2927, 2840, 1655, 1541, 1426, 1334, 1256, 1062, 807, 739; MS (ESI, 30 eV): m/z 637.19 [2 M+Na], 346.33 [M+K], 330.39 [M+Na], 308.41 [M+H]; HRMS (m/z): [M+H]+ calcd for C12H14N5O5, 308.0995. Found: 308.0948; 1H NMR (d6-DMSO, 40 C): delta 8.40 (s, 1H), 8.13 (d, J = 8.8 Hz, 2H), 7.68 (d, J = 9.2 Hz, 1H), 7.62 (d, J = 8.8 Hz, 2H), 7.61 (s, 1H), 7.00 and 6.99 (two s, 2H), 5.13 (d, J = 2.4 Hz, 1H), 4.22-4.15 (ddt, J = 2.4, 7.6 and 9.2 Hz, 1H), 3.66 (1H, dd, J = 7.6 and 10.8 Hz), 3.52 (1H, dd, J = 7.6 and 10.8 Hz); 13C NMR (d6-DMSO): delta 172.6, 158.1, 152.0, 146.9, 135.6, 127.6 (2C), 123.5 (2C), 69.4, 61.0, 56.7.

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 3163 - 3174

63
[ 4928-87-4 ]
[ 68-35-9 ]
N-{4-[(pyrimidin-2-yl)sulfamoyl]phenyl}-1H-1,2,4-triazole-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide;	Example 2. Synthesis of N-{4-[(pyrimidin-2-yl)sulfamoyl]phenyl}-lH-l,2,4- triazole-3-carboxamide, 1-18 1-18 [00267] Compound 1-18 was prepared according to the reaction sequence in Scheme IV with several adaptations. The solvent was removed in vacuo, the remaining material was triturated from H2O/CH3CN 1 : 1 (20ml), washed with small volumes of DMSO/CH3CN 1 :2, collected and dried to afford 190mg (65%) of N-{4-[(pyrimidin-2-yl)sulfamoyl]phenyl}-lH-l,2,4-triazole-3- carboxamide 1-18 as a colourless solid. 1H NMR (500 MHz, DMSO-d6) delta 14.84 (s, 1H), 11.70 (s, 1H), 10.83 (s, 1H), 8.66 (s, 1H), 8.50 (d, J = 4.9 Hz, 2H), 8.02 (d, J = 8.9 Hz, 2H), 7.95 (d, J = 8.9 Hz, 2H), 7.04 (t, J = 4.9 Hz, 1H).

Reference： [1]Patent: WO2016/40449,2016,A1 .Location in patent: Paragraph 00262; 00266-00267

64
[ 4928-87-4 ]
3-methyl-8-(6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-1-(piperidin-3-yl)-1H-imidazo[4,5-c]quinolin-2(3H)-one [ No CAS ]
1-(1-(1H-1,2,4-triazole-3-carbonyl)piperidin-3-yl)-3-methyl-8-(6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-2(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%		Example 2 1-(1-(1H-1,2,4-triazole-3-carbonyl)piperidin-3-yl)-3-methyl-8-(6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-2(3H)-one 20 mg (0.0455 mmol) of Compound 111, 6.2 mg (0.0546 mmol) of 1H-<strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong>, 9.23 mg (0.0683 mmol) of HOBt and 13.09 mg of EDCI were suspended in 2 ml of dichloromethane, added with 13.9 mg (0.137 mmol) of triethylamine, and stirred at room temperature for 4 h. TLC (DCM: MeOH = 10: 1) showed that most of the raw materials were not reacted. 9.3 mg of 1H-<strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong>, 26 mg of HATU and 15 mg of triethylamine were supplemented, and stirred at room temperature overnight. TLC (DCM: MeOH = 10: 1) showed that most of the raw materials were reacted completely. 10 mL of saturated sodium bicarbonate solution was added and stirred for 1 h. The organic phase was separated off, and the aqueous phase was extracted with 2 * 5 ml of dichloromethane. The organic phases were combined, dried, evaporated to dryness, and purified by preparative TLC (dichloromethane: methanol = 10: 1) to afford the target compound of Example 2 (17.8 mg), as a light yellow powder. Yield: 73%. LC-MS: 535 [M+1]+, tR = 1.463 min. 1H NMR (400 MHz, DMSO+D2O) delta 9.41 (d, J = 7.9 Hz, 1H), 9.14 (d, J = 6.0 Hz, 1H), 9.00 - 8.91 (m, 1H), 8.87 - 8.79 (m, 1H), 8.78 - 8.65 (m, 2H), 8.64 - 8.44 (m, 2H), 8.39 (s, 1H), 8.22 - 7.96 (m, 1H), 5.56 - 4.07 (m, 3H), 4.00 (d, J = 16.3 Hz, 3H), 3.60 (d, J = 13.2 Hz, 3H), 3.44 - 3.17 (m, 2H), 3.00 - 2.82 (m, 1H), 2.31 - 2.14 (m, 1H).

Reference： [1]Patent: EP3072893,2016,A1 .Location in patent: Paragraph 0089; 0090

65
[ 4928-87-4 ]
3-methyl-8-(6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-1-(pyrrolidin-3-yl)-1H-imidazo[4,5-c]quinolin-2(3H)-one hydrochloride [ No CAS ]
1-(1-(1H-1,2,4-triazole-3-carbonyl)pyrrolidin-3-yl)-3-methyl-8-(6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-2(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32%		Example 8 1-(1-(1H-1,2,4-triazole-3-carbonyl)pyrrolidin-3-yl)-3-methyl-8-(6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-2(3H)-one In an ice-water bath, 48.8 mg (0.43 mmol) of <strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong> and 200.76 mg (0.528 mmol) of 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate were dissolved in 5 mL of dichloromethane, added with 97 mg (0.96 mmol) of triethylamine and stirred at 0 C for 30 minutes, then added with 100 mg (0.24 mmol) of Intermediate 145 and stirred at room temperature overnight. The reaction was monitored by TLC. After the reaction was completed, 10 mL of saturated sodium bicarbonate aqueous solution was added, stirred for 20 minutes, and separated into layers. The aqueous phase was extracted with dichloromethane, and the organic phases were combined, dried, and rotary evaporated to dryness to afford a crude product. The crude product was purified with preparative silica gel plate (dichloromethane/methanol = 10/1, V/V) to afford the target compound of Example 8 (40 mg), as a white solid. Yield: 32%.

Reference： [1]Patent: EP3072893,2016,A1 .Location in patent: Paragraph 0114; 0115

66
[ 4928-87-4 ]
C₂₈H₂₄Cl₂N₄O [ No CAS ]
C₃₁H₂₅Cl₂N₇O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 5597 - 5601

67
[ 4928-87-4 ]
C₂₈H₂₄ClFN₄O [ No CAS ]
C₃₁H₂₅ClFN₇O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 5597 - 5601

68
[ 4928-87-4 ]
C₂₈H₂₃Cl₂FN₄O [ No CAS ]
C₃₁H₂₄Cl₂FN₇O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 5597 - 5601

69
[ 4928-87-4 ]
C₂₉H₂₆Cl₂N₄O₂ [ No CAS ]
C₃₂H₂₇Cl₂N₇O₃ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 5597 - 5601

70
[ 4928-87-4 ]
C₂₇H₂₃Cl₂N₅O [ No CAS ]
C₃₀H₂₄Cl₂N₈O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 5597 - 5601

71
[ 4928-87-4 ]
[ 674792-07-5 ]
tert-butyl 2,2-dimethyl-4-(1H-1,2,4-triazole-3-carbonyl)piperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a mixture of 1H-<strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong> (118 mg, 1.044 mmol) and HATU (429 mg, 1.13 mmol) in DMF (2.2 mL) was added DIPEA (325 muL, 1.87 mmol) and the mixture was stirred for 15 min. Then tert-butyl 2,2-dimethylpiperazine-1- carboxylate (200 mg, 0.93 mmol) is added followed by DIPEA (240 muL, 1.38 mmol) and the mixture was stirred for another 90 min. Saturated NH4Cl was added (5 mL), followed by EtOAc (10 mL). The layers were separated and the aqueous layer extracted with EtOAc (2 x 5 mL). The combined organic extracts were washed with brine (5 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel eluting with 0-15% MeOH: DCM affording the title compound (263 mg, 91% yield) as an off-white solid. ESI-MS m/z calc.309.18008, found 310.35 (M+1)+ Retention time: 1.22 minutes using method C

Reference： [1]Patent: WO2016/154075,2016,A1 .Location in patent: Paragraph 00351

72
[ 4928-87-4 ]
[7-tert-butyl-5-(4-fluoro-3-methylphenyl)furo[3,2-b]pyridin-2-yl]-(2,2-dimethylpiperazin-1-yl)methanone hydrochloride [ No CAS ]
(7-(tert-butyl)-5-(4-fluoro-3-methylphenyl)furo[3,2-b]pyridin-2-yl)(2,2-dimethyl-4-(1H-1,2,4-triazole-3-carbonyl)piperazin-1-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21%	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In 1-methyl-pyrrolidin-2-one; at 20℃; for 1h;	Intermediate W (75 mg, 0.15 mmol) was dissolved in NMP (841 muL) before HATU (75 mg, 0.20 mmol), 1H-<strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong> (21 mg, 0.18 mmol) and N-ethyl-N-isopropyl-propan-2-amine (105 muL, 0.60 mmol) were added. The solution was stirred at room temperature for 1h before aq. NH4Cl was added and the aq. phase was extracted twice with EtOAc. The combined organic phase was washed with sat.aq. NaHCO3 and brine, dried over MgSO4, filtered and the filtrate evaporated under reduced pressure. The residue was purified flash chromatography on silica gel eluting with 0-100% EtOAc: Hexanes affording the title compound. (7-(tert-Butyl)-5-(4-fluoro-3- methylphenyl)furo[3,2-b]pyridin-2-yl)(2,2-dimethyl-4-(1H-1,2,4-triazole-3- carbonyl)piperazin-1-yl)methanone (17 mg, 21% yield). 1H NMR (400 MHz, DMSO-d6) 8.68 (s, 1H), 8.07 - 7.99 (m, 1H), 7.94 (ddd, J = 8.0, 5.2, 2.4 Hz, 1H), 7.71 (d, J = 8.5 Hz, 1H), 7.48 (d, J = 9.8 Hz, 1H), 7.22 (td, J = 9.1, 3.7 Hz, 1H), 4.48 (s, 1H), 4.10 - 3.61 (m, 6H), 2.31 (t, J = 2.5 Hz, 3H), 1.61 - 1.39 (m, 15H). Signals doubled due to amide rotamers. ESI-MS m/z calc.518.2442, found 519.09 (M+1)+; Retention time: 3.30 minutes using method A

Reference： [1]Patent: WO2016/154075,2016,A1 .Location in patent: Page/Page column 261

73
[ 4928-87-4 ]
C₃₁H₂₇N₅O [ No CAS ]
1-(4-(1-(1H-1,2,4-triazol-3-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)phenyl)-3-methyl-8-(quinolin-3-yl)-1H-imidazo[4,5-c]quinolin-2-(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55.5%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 12h;	Take 0 · 15g (0.31 mmol)The intermediate 27 was dissolved in 30 ml of CHCl, and 0 · lg (0.52 mmol) of EDCI was added to obtain 0.2 g (0.27 mmol) of 1,2,4-triazol-3- Formic acid, stirred at room temperature12h, TLC detection. The reaction was completed and the crude product was dried and purified by silica gel column chromatography (eluent: methanol / dichloromethane / aqueous ammonia = 50:500: 1,7: ¥: ¥) to give a white solid. Example 21 Target product 0.1 g Yield 55.5%

Reference： [1]Patent: CN104411706,2016,B .Location in patent: Paragraph 0352-0354

74
[ 4928-87-4 ]
C₃₃H₂₇N₅O [ No CAS ]
1-[4-(8-(1H-1,2,4-triazole-3-carbonyl)-8-azabicyclo-[3.2.1]-oct-3-en-3-yl)phenyl]-3-methyl-8-(quinolin-3-yl)-1H-imidazo-[4,5-c]-quinolin-2-(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 12h;	0.178 (0.33 mmol) of intermediate 34 was dissolved in 30 mmol of 2 (12, added to zone 0.1 (0.5 mmol EDCl (: 1,0.07 g(0.23 mmol) of <strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong> was added and stirred at room temperature with stirring12h, TLC detection. The reaction was completed and the crude product was dried and purified by silica gel column chromatography (eluent: methanol / dichloromethane / aqueous ammonia = 50:500: 1, ¥ ¥: ¥) to give a white solid Example 26The target product was 0.12 g, yield 60%

Reference： [1]Patent: CN104411706,2016,B .Location in patent: Paragraph 0400-0402

75
[ 4928-87-4 ]
C₃₀H₂₈N₆O [ No CAS ]
1-(4-(4-(4H-1,2,4-triazole-3-carbonyl)piperazin-1-yl)phenyl)-3-methyl-8-(quinolin-3-yl)-1H-imidazo[4,5-c]quinolin-2-(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
36%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 12h;	A solution of intermediate 42 (0.288, 0.58 mmol) was dissolved in 50 mmol of HOBT(: 1 (0.178, 0.89 mmol)EDCl(0.118, 0.83 mmol)After stirring, lH-<strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong> (0.078, 0.62 mmol) was added at room temperatureStirring 12h, TLC detection, the end of the reaction, the liquid spin the crude product, the crude product by silica gel G column chromatography [eluent (methanol: dichloromethaneHexane: aqueous ammonia = 50: 500: 1 (nu: nu: nu)] to give 0.23 g of the title compound of Example 30-a, yield 36%

Reference： [1]Patent: CN104411706,2016,B .Location in patent: Paragraph 0438-0440

76
[ 4928-87-4 ]
C₃₃H₂₇N₅O [ No CAS ]
1-(4-(1-(1H-1,2,4-triazol-3-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)phenyl)-3-methyl-8-(6-phenylpyridin-3-yl)-1H-imidazo[4,5-c]quinolin-2-(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
33.3%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 12h;	The intermediate 27a was added(0.2 g, 0.39 mmol) was dissolved in 35 ml of DMF, EDCI (0.08 g, 0.42 mmol) was added,HOBT, (0.058, 0.38 mmol) was dissolved with stirring, and then ml, 2,4-triazole-3-carboxylic acid (0.058,0.44mmo 1), DIEA 0.2ml (1.17mmo 1), stirring at room temperature for 12h, TLC detection, the end of the reaction, the liquid spin dry crude, crudeThe product was purified by silica gel G column chromatography [eluent (methanol: dichloromethane) = 50: 500 (nu: nu)] to give the title compound0 · 08g, yield 33.3%

Reference： [1]Patent: CN104411706,2016,B .Location in patent: Paragraph 0470-0472

77
[ 4928-87-4 ]
C₂₉H₂₇N₅O₂ [ No CAS ]
1-(4-(1-(1H-1,2,4-triazol-3-carbonyl)-1,2,3,6-tetrahydropyridin-4-yl)phenyl)-8-(6-methoxy-5-methylpyridin-3-yl)-3-methyl-1H-imidazo[4,5-c]quinolin-2-(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30.3%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 12h;	A solution of intermediate 27b (0.26 g, 0.58 mmol) in 15 ml of DMF was added EDCI (0.17 g, 0.89 mmol)(0 · 12g, 0 · 89mmo 1) After stirring and dissolving, 1H-<strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong> (0.55 g, 0.44 mmo 1)DIEA 0.2ml (1.17mmol), stirring at room temperature for 12h, TLC detection, the end of the reaction, the liquid spinning was crude, crude by silica gel GColumn chromatography [eluent (methanol: dichloromethane) = 50: 500 (nu: nu)] to give 0.1 g of the title compound of Example 34,Yield: 30.3%

Reference： [1]Patent: CN104411706,2016,B .Location in patent: Paragraph 0480-0482

78
[ 4928-87-4 ]
3-methyl-8-(6-(1-methyl-1H-pyrazol-4-yl)pyridin-(4-piperidin-3-yl)phenyl)-1H-imidazo[4,5-c]quinolin-2(3H)-one hydrochloride [ No CAS ]
1-(4-(1-(1H-1,2,4-triazol-3-carbonyl)piperidin-3-yl)phenyl)-3-methyl-8-(6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-2-(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21%	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine; In dichloromethane; at 0 - 20℃; for 0.5h;	10.9 mg (0.077 mmol) of <strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong> was dissolved in 5 ml of dichloromethane and 45.2 mg(0.119 mmol) of 2- (7-azobenzotriazole-Nu, Nu, N ', N'-tetramethyluronium hexafluorophosphate under ice bath was added 21.9 mg(0.216 mmol) of triethylamine,Stirring for 30min,30 mg of intermediate 121 (0.054 mmol) was added,Stir overnight at room temperature. TLC checkMeasurement,After the reaction,Add lml of saturated sodium bicarbonate solution,Stirring for 20min,Dispensing,The aqueous phase was extracted with dichloromethane,mergeThe organic phase,dry,Steamed in crude.The crude product was purified by preparative silica gel plate (methanol: dichloromethane = 1: 10)The target compound was 9 mg in 21%

Reference： [1]Patent: CN104411706,2016,B .Location in patent: Paragraph 0571-0573

79
[ 4928-87-4 ]
3-methyl-8-(6-(1-methyl-1H-pyrazol-4-yl)3-yl)-1-(4-(piperidin-4-yl)phenyl)-1H-imidazo[4,5-c]quinolin-2-(3H)-one [ No CAS ]
1-(4-(1-(1H-124-triazol-3-carbonyl)piperidin-4-yl)phenyl)-3-methyl-8-(6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-2(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
8.4%	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine; In dichloromethane; at 0 - 20℃; for 0.5h;	Under ice-water bath, 39.4 mg (0.349 mmol)<strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong> and 16.28 mg (0.426 mmol)2- (7-azobenzotriazole) -Nu, Nu, N, N-tetramethyluronium hexafluorophosphate was dissolved in 5 mL of dichloromethane(0.96 mmol) of triethylamine was added, and after stirring at 0 C for 30 minutes, 100 mg (0.194 mmol) of intermediate 130 was added,Stir the temperature overnight. TLC, after the completion of the reaction, 10 mL of saturated aqueous sodium bicarbonate solution was added, stirred for 20 minutes, separated, the aqueous phaseExtraction with methylene chloride, combined organic phase, dry, spin dry to obtain crude. The crude product was purified by preparative silica gel plate (dichloromethane / AAlcohol = 10/1, V / V) to give 10 of the title compound as a white solid in a yield of 8.4%

Reference： [1]Patent: CN104411706,2016,B .Location in patent: Paragraph 0619-0621

80
[ 4928-87-4 ]
3-ethyl-8-(6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-1-(4-(piperidin-4-yl)phenyl)-1H-imidazo[4,5-c]quinolin-2-(3H)-one [ No CAS ]
1-(4-(1-(4H-1,2,4-triazol-3-carbonyl)piperidin-4-yl)phenyl)-3-ethyl-8-(6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-2(3H)one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21.2%	With hydrogenchloride; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In water; at 20℃;	A mixture of 50 mg (0.045 mmol) of compound 136 hydrochloride, 18.8 mg (0.166 mmol) of 1 H-1,2,4-triazol-22.4 mg (0.166 mmol)H0Bt and 31.8 mg EDCISuspended in 4mlTwo gas a burning,Add 58.8 mg(0.581 mmol) of triethylamine,Stirred at room temperature overnight,TLC (DCM: Me0H = 10: l)Showing that most of the raw materials did not react,Additional10 mg of 1H-<strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong>,47 mg of HATU and 30 mg of triethylamine,Stirred at room temperature overnight,TLC (DCM: Mu0Eta =10: 1) shows most of the raw material reaction finished,Add 15ml saturated sodium bicarbonate solution for 0.5 hours, the organic phase, the water phase(5: 10) dichloromethane methanol mixture (about 10: 1) extraction, and then 2 1 10 ml of dichloromethane extraction, combined organic phase, dryDry, filtered, evaporated to dryness, preparative TLC purification (dichloromethane: methanol = 10: 1)To give the title compound of Example 51,11mg light yellowThe yield was 21.2%.

Reference： [1]Patent: CN104411706,2016,B .Location in patent: Paragraph 0640-0642

81
[ 4928-87-4 ]
C₃₁H₂₇N₅O [ No CAS ]
1-(4-(1-(4H-1,2,4-triazol-3-carbonyl)piperidin-4-yl)phenyl)-3-methyl-8-(quinolin-3-yl)-1H-imidazo[4,5-c]quinolin-2-(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55.6%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 12h;	0.15 g (0.31 mmol) of intermediate 20 was dissolved in 30 ml CH2CI2, 0.1 g (0.52 mmol) of EDCI, 0.07 g (0.53 mmol)Eta0BetaTau,After stirring to dissolve, 0.03 g (0.27 mmol)<strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong>, stirred at room temperature12h, TLC detection. The reaction was carried out and the crude product was dried and purified by silica gel column chromatography (eluent: methanol / dichloromethane / aqueous ammonia = 50: 500: 1, ¥: ¥ ¥) to give a white solid. Example 16The target product, 0.1 g, yield 55.6%

Reference： [1]Patent: CN104411706,2016,B .Location in patent: Paragraph 0318-0320

82
[ 4928-87-4 ]
2-amino-5,5,7,7-tetramethyl-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid amide [ No CAS ]
N-(3-carbamoyl-5,5,7,7-tetramethyl-5,7-dihydro-4H-thieno[2,3-c]pyran-2-yl)-1H-1,2,4-triazole-3-carboxamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 1425 - 1435

83
[ 4928-87-4 ]
manganese(II) chloride tetrahydrate [ No CAS ]
[ 7732-18-5 ]
[Mn(1H-1,2,4-triazole-3-carboxylate)₂(H₂O)₂] [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52.2%	With 1,3-bis(1,2,4-triazol-1-yl)propane; at 20℃; for 6h;	MnCl2·4H2O (0.198 g, 1.0 mmol) in 3.0 mL of aqueous solution wasslowly added into a flask containing H3dctrz (0.078 g, 0.5 mmol) andpbtrz (0.08 g, 0.5 mmol) in 10.0 mL of aqueous solution. The reactingsolution was kept stirring for 6.0 h. The precipitate was filtrated, andcolourless crystals were isolated from the filtrate within 6 weeks. Yield:0.164 g (52.2% based on Mn(II)). Elemental analysis (EA) for calcd. 1(C6H8N6O6Mn, 315.12): C 16.96, H 1.78, N 22.25; found: C 17.34H 1.94, N 21.22%. IR (cm-1, s = strong, m = medium, w = weak): 3361s,3122s, 1625s, 1476s, 1411s, 1368w, 1353w, 1296s, 1162w, 1012m,984w, 892w, 841m, 670 m.

Reference： [1]Journal of Solid State Chemistry,2018,vol. 262,p. 351 - 359

84
[ 34550-41-9 ]
[ 4928-87-4 ]

Reference： [1]Journal of Solid State Chemistry,2018,vol. 262,p. 351 - 359

85
[ 4928-87-4 ]
4-(2-((5-chloro-2-propoxybenzyl)amino)ethyl)-N-(prop-2-yn-1-yl)benzenesulfon-amide [ No CAS ]
N-(5-chloro-2-propoxybenzyl)-N-(4-(N-(prop-2-yn-1-yl)-sulfamoyl)phenethyl)-1H-1,2,4-triazole-3-carboxamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2019,vol. 62,p. 9718 - 9731

86
[ 4928-87-4 ]
[ 769-92-6 ]
N-(4-(tert-butyl)phenyl)-1H-1,2,4-triazole-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 16h;Inert atmosphere;	General procedure: The tail group amines Ar-NH2 (Ar a-d) (19.5 mmol,1.1 equiv) were added to a stirring solution of <strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong> 12 (2.00 g, 17.7 mmol, 1.0 equiv) in dry DMF(30 mL) at room temperature. After 5 min, TBTU (6.0 g, 18.6 mmol,1.0 equiv) and DIPEA (11.0 mL, 61.9 mmol, 3.5 equiv) were added insequence. The resulting solution was stirred at room temperaturefor 16 h. After completion of the reaction, as indicated by TLC, DMFwas removed by rotary evaporation at 30 torr and 70 C. The crudematerial was purified by methods described in each individualentry.
25%	With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; for 24h;Inert atmosphere;	To a reaction of H-, 2, 4-triazole-3 -carboxylic acid (226 mg, 2.0 mmol) and 4- (tert-butyl)aniline (0.33 mL, 2.1 mmol) in dry DMF (10 mL) was added 1- hydroxybenzotriazole monohydrate (337 mg, 2.2 mmol) and EDC (N-(3- Dimethylaminopropyl)-N'-ethylcarbodiimide) (422 mg, 2.2 mmol) followed by N- methylmorpholine (0.88 mL, 8.0 mmol via syringe). The mixture was stirred at room temperature under nitrogen and the solids were gradually dissolved. The contents were stirred at room temperature for 24.0 h, and then slowly diluted into iced water and extracted with DCM (2 x 50 mL). The DCM phase was washed with ice cold water (2 x 100 mL). The DCM phase was dried over anhydrous Na2S04, filtered and concentrated under reduced pressure and chromatographed on silica gel using EtOAc and Hexanes (60:40) as eluents to get the desired amide 13 (123 mg, 25 % yield) as a white solid compound. -NMR (400 MHz, DMSO-de): (br s, 1H), 7.74 (d, J= 8.8 Hz, 2H), 7.37 (d, J= 8.4 Hz, 2H), 1.28 (s, 9H) ppm. MH+ = 245.2 m/z.

Reference： [1]European Journal of Medicinal Chemistry,2020,vol. 189
[2]Patent: WO2020/41556,2020,A1 .Location in patent: Page/Page column 30; 39-40

87
[ 4928-87-4 ]
[ 108-91-8 ]
N-cyclohexyl-1H-1,2,4-triazole-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 16h;Inert atmosphere;	General procedure: The tail group amines Ar-NH2 (Ar a-d) (19.5 mmol,1.1 equiv) were added to a stirring solution of <strong>[4928-87-4]1,2,4-triazole-3-carboxylic acid</strong> 12 (2.00 g, 17.7 mmol, 1.0 equiv) in dry DMF(30 mL) at room temperature. After 5 min, TBTU (6.0 g, 18.6 mmol,1.0 equiv) and DIPEA (11.0 mL, 61.9 mmol, 3.5 equiv) were added insequence. The resulting solution was stirred at room temperaturefor 16 h. After completion of the reaction, as indicated by TLC, DMFwas removed by rotary evaporation at 30 torr and 70 C. The crudematerial was purified by methods described in each individualentry.

Reference： [1]European Journal of Medicinal Chemistry,2020,vol. 189

88
[ 4928-87-4 ]
[ 4393-09-3 ]
N-(2,3-dimethoxybenzyl)-1H-1,2,4-triazole-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20%	With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; for 24h;Inert atmosphere;	To a reaction of 1/7-1, 2, 4-triazole-3 -carboxylic acid (226 mg, 2.0 mmol) and (2,3- dimethoxybenzyl)amine (0.31 mL, 2.1 mmol) in dry DMF (10 mL) was added 1- hydroxybenzotriazole monohydrate (337 mg, 2.2 mmol) and EDC (N-(3- Dimethylaminopropyl)-N'-ethylcarbodiimide) (422 mg, 2.2 mmol) followed by N- methylmorpholine (0.88 mL, 8.0 mmol via syringe). The mixture was stirred at room temperature under nitrogen and the solids were gradually dissolved. The contents were stirred at room temperature for 24 h, and then slowly diluted into ice cold water and extracted with DCM (2 x 50 mL). The DCM phase was washed with ice cold water (2 x 100 mL). The DCM phase was dried over anhydrous Na2S04, filtered and concentrated under reduced pressure and chromatographed on silica gel using EtOAc and Hexanes (9: 1) as eluents to get the desired amide 3 (104.9 mg, 20% yield) as a white solid. -NMEI (400 MHz, DMSO-de): <514.67 (br s, 1H), 8.94 (br s, 1H), 8.49 (br s, 1H), 7.03-6.99 (m, 1H), 6.99-6.94 (m, 1H), 6.85-6.82 (m, 1H), 4.48 (d, J= 6.4 Hz, 2H), 3.80 (s, 3H), 3.78 (s, 3H) ppm. MH+ = 233.2 m/z.

Reference： [1]Patent: WO2020/41556,2020,A1 .Location in patent: Page/Page column 30; 34

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Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Ghs Hazard Statements

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere