[ CAS No. 55864-87-4 ] {[proInfo.proName]}

Name: 55864-87-4|Ethyl 4-nitro-1H-pyrazole-3-carboxylate|95%
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Quality Control of [ 55864-87-4 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 55864-87-4 ]

Product Details of [ 55864-87-4 ]

CAS No. :	55864-87-4	MDL No. :	MFCD00195040
Formula :	C₆H₇N₃O₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	GNGKEGKMDXAMKJ-UHFFFAOYSA-N
M.W :	185.14	Pubchem ID :	338416
Synonyms :

Calculated chemistry of [ 55864-87-4 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	5
Fraction Csp3 :	0.33
Num. rotatable bonds :	4
Num. H-bond acceptors :	5.0
Num. H-bond donors :	1.0
Molar Refractivity :	43.5
TPSA :	100.8 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) :	-7.0 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.63
Log Po/w (XLOGP3) :	0.6
Log Po/w (WLOGP) :	0.49
Log Po/w (MLOGP) :	-1.0
Log Po/w (SILICOS-IT) :	-0.96
Consensus Log Po/w :	-0.05

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.39
Solubility :	7.6 mg/ml ; 0.0411 mol/l
Class :	Very soluble
Log S (Ali) :	-2.29
Solubility :	0.948 mg/ml ; 0.00512 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-1.1
Solubility :	14.8 mg/ml ; 0.0798 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.32

Safety of [ 55864-87-4 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 55864-87-4 ]

* 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 [ 55864-87-4 ]
Downstream synthetic route of [ 55864-87-4 ]

[ 55864-87-4 ] Synthesis Path-Upstream 1~3

1
[ 64-17-5 ]
[ 5334-40-7 ]
[ 55864-87-4 ]

Yield	Reaction Conditions	Operation in experiment
98%	Reflux	A solution of 4-nitro-1H-pyrazole-3-carboxylic acid (2.5 g, 15.9 mmol) in ethanolic HCl (38.3 mL, 1.25M) was refluxed overnight. All volatiles were removed to yield a whitesolid (2.9 g, 98percent) which was used without any further purification. MS: M=186.1 (M+H)⁺
98%	Reflux; Inert atmosphere	A solution of 4-nitro-lH-pyrazole-3-carboxylic acid (2.5 g, 15.9 mmol) in ethanolic HQ (38.3 mL, 1.25M) was refluxed overnight. All volatiles were removed to yield a white solid (2.9 g, 98 percent) which was used without any further purification.MS: M = 186.1 (M+H)⁺
96%	at 20℃; for 48 h;	Thionyl chloride (2.90 ml, 39.8 mmol) was slowly added to a mixture of 4-nitro-3- pyrazolecarboxylic acid (5.68 g, 36.2 mmol) in EtOH (100 ml) at ambient temperature and the mixture stirred for 48 h. The mixture was reduced in vacuo and EPO <DP n="124"/>dried through azeotrope with toluene to afford 4-nitro-lH-pyrazole-3-carboxylic acid ethyl ester as a white solid (6.42 g, 96percent). (¹H NMR (400 MHz, DMSOd₆) δ 14.4 (s, IH), 9.0 (S₅ IH)₃ 4.4 (q, 2H), 1.3 (t, 3H)).

96%	at 20℃; for 48 h;	1A. 4-Nitro-lH-pyrazole-3-carboxylic acid ethyl ester; OEtN-NHThionyl chloride (2.90 ml, 39.8 mmol) was slowly added to a mixture of 4-nitro-3-pyrazolecarboxylic acid (5.68 g, 36.2 mmol) in EtOH (100 ml) at ambienttemperature and the mixture stirred for 48 h. The mixture was reduced in vacuaand dried through azeotrope with toluene to afford 4-nitro-lH-pyrazole-3-carboxylic acid ethyl ester as a white solid (6.42 g, 96percent). (*H NMR (400 MHz,DMSO-d₆) 8 14.4 (s, 1H), 9.0 (s, 1H), 4.4 (q, 2H), 1.3 (t, 3H)).
96%	at 20℃; for 48 h;	Preparation VIII; Synthesis of 4-ammo-1H-pyrazole-3-carboxylic acid ethyl esterStep 1. 4-Nitro-1H-pyrazole-3-carboxylic acid ethyl esterThionyl chloride (2.90 ml, 39.8 mmol) was slowly added to a mixture of 4-nitro-3- pyrazolecarboxylic acid (5.68 g, 36.2 mmol) in EtOH (100 ml) at ambient temperature and the mixture stirred for 48 hours. The mixture was reduced in vacuo and dried through azeotrope with toluene to afford 4-nitro-1H-pyrazole-3- carboxylic acid ethyl ester as a white solid (6.42 g, 96percent). (¹H NMR (400 MHz, DMSO-d₆) δ 14.4 (s, IH), 9.0 (s, IH), 4.4 (q, 2H), 1.3 (t, 3H)).
96%	at 20℃; for 48 h;	Thionyl chloride (2.90 ml, 39.8 mmol) was slowly added to a mixture of 4-nitro-3-pyrazolecarboxylic acid (5.68 g, 36.2 mmol) in EtOH (100 ml) at ambient temperature and the mixture stirred for 48 h. The mixture was reduced in vacuo and dried through azeotrope with toluene to afford 4-nitro-1H-pyrazole-3-carboxylic acid ethyl ester as a white solid (6.42 g, 96percent). (¹H NMR (400 MHz, DMSO-d₆) D 14.4 (s, 1 H), 9.0 (s, 1 H), 4.4 (q, 2H), 1.3 (t, 3H)).
96%	at 20℃; for 48 h;	Thionyl chloride (2.90 ml, 39.8 mmol) was slowly added to a mixture of 4-nitro-3-pyrazolecarboxylic acid (5.68 g, 36.2 mmol) in EtOH (100 ml) at ambient temperature and the mixture stirred for 48 h. The mixture was reduced in vacuo and dried through azeotrope with toluene to afford 4-nitro-1H-pyrazole-3-carboxylic acid ethyl ester as a white solid (6.42 g, 96percent). (¹H NMR (400 MHz, DMSO-d₆) D 14.4 (s, 1 H), 9.0 (s, 1 H), 4.4 (q, 2H), 1.3 (t, 3H)).
96%	at 20℃; for 48 h;	Step 1. 4-Nitro-lH-pyrazole-3-carboxylic acid ethyl ester; Thionyl chloride (2.90 ml, 39.8 mmol) was slowly added to a mixture of 4-nitro-3- pyrazolecarboxylic acid (5.68 g, 36.2 mmol) in EtOH (100 ml) at ambient temperature and the mixture stirred for 48 hours. The mixture was reduced in vacuo and dried through azeotrope with toluene to afford 4-nitro-lH-pyrazole-3- carboxylic acid ethyl ester as a white solid (6.42 g, 96percent). (¹H NMR (400 MHz, DMSO-d₆) δ 14.4 (s, IH), 9.0 (s, IH), 4.4 (q, 2H), 1.3 (t, 3H)).

Reference： [1] Patent: US2011/306589, 2011, A1, . Location in patent: Page/Page column 45
[2] Patent: WO2011/154327, 2011, A1, . Location in patent: Page/Page column 118
[3] Patent: WO2006/70198, 2006, A1, . Location in patent: Page/Page column 122-123
[4] Patent: WO2006/3440, 2006, A1, . Location in patent: Page/Page column 147
[5] Patent: WO2006/77414, 2006, A1, . Location in patent: Page/Page column 142
[6] Patent: WO2006/77424, 2006, A1, . Location in patent: Page/Page column 186
[7] Patent: WO2006/77425, 2006, A1, . Location in patent: Page/Page column 186
[8] Patent: WO2006/77428, 2006, A1, . Location in patent: Page/Page column 163
[9] Patent: WO2008/7123, 2008, A2, . Location in patent: Page/Page column 111
[10] Journal of Medicinal Chemistry, 2008, vol. 51, # 16, p. 4986 - 4999
[11] Patent: WO2005/37797, 2005, A1, . Location in patent: Page/Page column 271-272

2
[ 5334-40-7 ]
[ 55864-87-4 ]

Yield	Reaction Conditions	Operation in experiment
96%	With thionyl chloride In ethanol at 20℃; for 48 h;	Thionyl chloride (2.90 ml, 39.8 mmol) was slowly added to a mixture of 4-nitro-3- pyrazolecarboxylic acid (5.68 g, 36.2 mmol) in EtOH (100 ml) at ambient temperature and the mixture stirred for 48 h. The mixture was reduced in vacuo and dried through azeotrope with toluene to afford 4-nitro-1H-pyrazole-3-carboxylic acid ethyl ester as a white solid (6.42 g, 96percent). (¹H NMR (400 MHz, DMSO-d₆) δ 14.4 (s, 1H), 9.0 (s, 1H), 4.4 (q, 2H), 1.3 (t, 3H)).

Reference： [1] Patent: WO2005/12256, 2005, A1, . Location in patent: Page/Page column 184
[2] Patent: WO2007/23105, 2007, A1, . Location in patent: Page/Page column 63-64

3
[ 75-36-5 ]
[ 5334-40-7 ]
[ 55864-87-4 ]

Reference： [1] Patent: US2005/197340, 2005, A1, . Location in patent: Page/Page column 68

[ 55864-87-4 ] Synthesis Path-Downstream 1~38

1
[ 55864-87-4 ]
[ 55904-61-5 ]

Yield	Reaction Conditions	Operation in experiment
98%	With hydrogen;palladium 10% on activated carbon; In ethanol; for 20h;	A mixture of 4-nitro-lH-pyrazole-3-carboxylic acid ethyl ester (6.40 g, 34.6 mmol) and 10% Pd/C (650 mg) in EtOH (150ml) was stirred under an atmosphere of hydrogen for 20 h. The mixture was filtered through a plug of Celite, reduced in vacuo and dried through azeotrope with toluene to afford 4-amino-lH-pyrazole-3- carboxylic acid ethyl ester as a pink solid (5.28 g, 98%). (1H NMR (400 MHz, DMSOd6) delta 12.7 (s, IH)5 7.1 (s, IH), 4.8 (s, 2H)5 4.3 (q, 2H), 1.3 (t, 3H)).
98%	With hydrogen;10% palladium on activated carbon; In ethanol; for 20h;	Step 2. 4-Amino-1H-pyrazole-3-carboxylic acid ethyl ester EPO <DP n="144"/>A mixture of <strong>[55864-87-4]4-nitro-1H-pyrazole-3-carboxylic acid ethyl ester</strong> (6.40 g, 34.6 mmol) and 10% Pd/C (650 mg) in EtOH (150ml) was stirred under an atmosphere of hydrogen for 20 hours. The mixture was filtered through a plug of Celite, reduced in vacuo and dried through azeotrope with toluene to afford 4-amino-1H-pyrazole- 3-carboxylic acid ethyl ester as a pink solid (5.28 g, 98%). (1H NMR (400 MHz, DMSO-d6) delta 12.7 (s, IH), 7.1 (s, IH)5 4.8 (s, 2H), 4.3 (q, 2H), 1.3 (t, 3H)).
98%	With hydrogen;palladium 10% on activated carbon; In ethanol; for 20h;	IB. Synthesis of 4-Amino-lH-pyrazole-3-carboxylic acid ethyl ester; NH2 // OEtN-NHA mixture of 4-nitro-lH-pyrazole-3-carboxylic acid ethyl ester (6.40 g, 34.6 mmol)and 10% Pd/C (650 mg) in EtOH (150ml) was stirred under an atmosphere ofhydrogen for 20 h. The mixture was filtered through a plug of Celite, reduced invacua and dried through azeotrope with toluene to afford 4-amino-lH-pyrazole-3-carboxylic acid ethyl ester as a pink solid (5.28 g, 98%). (.H NMR (400 MHz,DMSO-d6) 5 12.7 (s, 1H), 7.1 (s, 1H), 4.8 (s, 2H), 4.3 (q, 2H), 1.3 (t, 3H)).

98%	With hydrogen;palladium 10% on activated carbon; In ethanol; for 20h;	A mixture of <strong>[55864-87-4]4-nitro-1H-pyrazole-3-carboxylic acid ethyl ester</strong> (6.40 g, 34.6 mmol) and 10% Pd/C (650 mg) in EtOH (150ml) was stirred under an atmosphere of hydrogen for 20 h. The mixture was filtered through a plug of Celite, reduced in vacuo and dried through azeotrope with toluene to afford 4-amino-1H-pyrazole-3- carboxylic acid ethyl ester as a pink solid (5.28 g, 98%). (1H NMR (400 MHz1 DMSO-d6) D 12.7 (s, 1 H), 7.1 (s, 1 H), 4.8 (s, 2H), 4.3 (q, 2H), 1.3 (t, 3H)).
98%	With hydrogen;palladium 10% on activated carbon; In ethanol; for 20h;	A mixture of <strong>[55864-87-4]4-nitro-1H-pyrazole-3-carboxylic acid ethyl ester</strong> (6.40 g, 34.6 mmol) and 10% Pd/C (650 mg) in EtOH (150ml) was stirred under an atmosphere of hydrogen for 20 h. The mixture was filtered through a plug of Celite, reduced in vacuo and dried through azeotrope with toluene to afford 4-amino-1H-pyrazole-3- carboxylic acid ethyl ester as a pink solid (5.28 g, 98%). (1H NMR (400 MHz1 DMSO-d6) D 12.7 (s, 1 H), 7.1 (s, 1 H), 4.8 (s, 2H), 4.3 (q, 2H), 1.3 (t, 3H)).
98%	With hydrogen;palladium 10% on activated carbon; In ethanol; for 20h;	Step 2. 4-Amino-lH-pyrazole-3-carboxylic acid ethyl ester ; <n="113"/>A mixture of 4-nitro-lH-pyrazole-3-carboxylic acid ethyl ester (6.40 g, 34.6 mmol, prepared analogous to Preparation I) and 10% Pd/C (650 mg) in EtOH (150ml) was stirred under an atmosphere of hydrogen for 20 hours. The mixture was filtered through a plug of Celite, reduced in vacuo and dried through azeotrope with toluene to afford 4-amino-lH-pyrazole-3-carboxylic acid ethyl ester as a pink solid (5.28 g, 98%). (1HNMR (400 MHz, DMSOd6) delta 12.7 (s, IH), 7.1 (s, IH), 4.8 (s, 2H), 4.3 (q, 2H), 1.3 (UH)).
98%	With hydrogen;palladium 10% on activated carbon; In ethanol; for 20h;	A mixture of <strong>[55864-87-4]4-nitro-1H-pyrazole-3-carboxylic acid ethyl ester</strong> (6.40 g, 34.6 mmol) and 10% Pd/C (650 mg) in EtOH (150ml) was stirred under an atmosphere of hydrogen for 20 h. The mixture was filtered through a plug of Celite, reduced in vacuo and dried through azeotrope with toluene to afford 4-amino-1H-pyrazole-3- carboxylic acid ethyl ester as a pink solid (5.28 g, 98%). (1H NMR (400 MHz, DMSO-d6) delta 12. 7 (s, 1H), 7.1 (s, 1H), 4. 8 (s, 2H), 4.3 (q, 2H), 1.3 (t, 3H)).

Reference： [1]Patent: WO2006/70198,2006,A1 .Location in patent: Page/Page column 123
[2]Patent: WO2006/77414,2006,A1 .Location in patent: Page/Page column 142-143
[3]Patent: WO2006/3440,2006,A1 .Location in patent: Page/Page column 147-148
[4]Patent: WO2006/77424,2006,A1 .Location in patent: Page/Page column 186
[5]Patent: WO2006/77428,2006,A1 .Location in patent: Page/Page column 163-164
[6]Patent: WO2008/7123,2008,A2 .Location in patent: Page/Page column 111-112
[7]Journal of Medicinal Chemistry,2008,vol. 51,p. 4986 - 4999
[8]Patent: WO2005/12256,2005,A1 .Location in patent: Page/Page column 184
[9]Journal of Organic Chemistry,1992,vol. 57,p. 4690 - 4696

2
[ 55864-87-4 ]
[ 106-96-7 ]
[ 503821-47-4 ]

Reference： [1]Archiv der Pharmazie,2002,vol. 335,p. 339 - 346
[2]Medicinal Chemistry Research,2002,vol. 11,p. 333 - 344

3
[ 55864-87-4 ]
[ 57-13-6 ]
[ 14215-97-5 ]
[ 74-88-4 ]
[ 565432-23-7 ]
[ 565432-22-6 ]

Reference： [1]Nucleosides, nucleotides and nucleic acids,2005,vol. 24,p. 1947 - 1970

4
[ 55864-87-4 ]
4-nitro-1-[4-(4-phenyl-piperazin-1-yl)-but-2-ynyl]-1<i>H</i>-pyrazole-3-carboxylic acid ethyl ester [ No CAS ]

Reference： [1]Medicinal Chemistry Research,2002,vol. 11,p. 333 - 344

5
[ 55864-87-4 ]
1-[4-(4-benzyl-piperazin-1-yl)-but-2-ynyl]-4-nitro-1<i>H</i>-pyrazole-3-carboxylic acid ethyl ester [ No CAS ]

Reference： [1]Medicinal Chemistry Research,2002,vol. 11,p. 333 - 344

6
[ 55864-87-4 ]
diethyl-[4-(3-ethoxycarbonyl-4-nitro-1H-pyrazol-1-yl)but-2-ynyl]amine [ No CAS ]

Reference： [1]Archiv der Pharmazie,2002,vol. 335,p. 339 - 346

7
[ 55864-87-4 ]
3-ethoxycarbonyl 4-nitro-1-(4-pyrrolidin-1-yl-but-2-ynyl)-1H-pyrazole [ No CAS ]

Reference： [1]Archiv der Pharmazie,2002,vol. 335,p. 339 - 346

8
[ 20781-20-8 ]
[ 55864-87-4 ]
2,4-dimethoxybenzylamine salt of N-(2,4-dimethoxybenzyl)-4-nitro-1H-pyrazole-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; at 120℃; for 1.5h;	[00847] Step 2: Preparation of N-(2, 4-Dimethoxybenzyl)-4-nitro-1H- pyrazole-3-carboxamide; [00849] The carboxylate from Step 1 (3.32 g, 17.93 mmol) was stirred in excess 2, 4-dimethoxybenzylamine at 120 C for 1.5 h. The resulting product was triturated with hot EtOH and filtered to give 8.45 g of product as the 2,4- dimethoxybenzylamine salt (1: 1). The salt was dissolve in MeOH (300 mL, 60 C for 0.5 h), acidified using conc. HCI and diluted to a total volume of 1 L with water. The resulting precipitate was filtered, rinsed with water and air-dried to give an off-white solid.'H NMR (300 MHz, DMSO-d6) : No. 3.74 (s, 3 H), 3.79 (s, 3 H), 4.33 (d, 2 H), 6.50 (m, 2 H), 7.19 (d, 1 H), 8. 8 (br s, 1 H), 8.87 (br s, 1 H), 14.05 (br s, 1 H); MS (ESI+) for C, 3H, 4N4O5 m/z 307.0 (M+H) +.

Reference： [1]Patent: WO2005/37797,2005,A1 .Location in patent: Page/Page column 272-273

9
[ 64-17-5 ]
[ 5334-40-7 ]
[ 55864-87-4 ]

Yield	Reaction Conditions	Operation in experiment
98%	With hydrogenchloride;Reflux;	A solution of 4-nitro-1H-pyrazole-3-carboxylic acid (2.5 g, 15.9 mmol) in ethanolic HCl (38.3 mL, 1.25M) was refluxed overnight. All volatiles were removed to yield a whitesolid (2.9 g, 98percent) which was used without any further purification. MS: M=186.1 (M+H)+
98%	With hydrogenchloride;Reflux; Inert atmosphere;	A solution of 4-nitro-lH-pyrazole-3-carboxylic acid (2.5 g, 15.9 mmol) in ethanolic HQ (38.3 mL, 1.25M) was refluxed overnight. All volatiles were removed to yield a white solid (2.9 g, 98 percent) which was used without any further purification.MS: M = 186.1 (M+H)+
98%	With thionyl chloride; at 20℃; for 2h;Cooling with ice;	4-Nitropyrazole-3-carboxylic acid (5.00 g, 31.8 mmol) was added to a 100 mL single-mouth bottle, dissolved in 40 mL of absolute ethanol, and cooled in an ice bath for 10 min.Thionyl chloride (2.78 mL, 38.2 mmol) was added dropwise, and the mixture was transferred to room temperature for 2 h. The reaction was completed by TLC. The solvent was evaporated to dryness to give pale brown solid, 30mL of water, 30 min. The pale yellow solid was obtained. The filtrate was extracted twice with 20 mL of EA.The filtrate was spun and the combined solids were combined to give 5.82 g. Yield 98percent,

96%	With thionyl chloride; at 20℃; for 48h;	Thionyl chloride (2.90 ml, 39.8 mmol) was slowly added to a mixture of 4-nitro-3- pyrazolecarboxylic acid (5.68 g, 36.2 mmol) in EtOH (100 ml) at ambient temperature and the mixture stirred for 48 h. The mixture was reduced in vacuo and EPO <DP n="124"/>dried through azeotrope with toluene to afford 4-nitro-lH-pyrazole-3-carboxylic acid ethyl ester as a white solid (6.42 g, 96percent). (1H NMR (400 MHz, DMSOd6) delta 14.4 (s, IH), 9.0 (S5 IH)3 4.4 (q, 2H), 1.3 (t, 3H)).
96%	With thionyl chloride; at 20℃; for 48h;	1A. 4-Nitro-lH-pyrazole-3-carboxylic acid ethyl ester; OEtN-NHThionyl chloride (2.90 ml, 39.8 mmol) was slowly added to a mixture of 4-nitro-3-pyrazolecarboxylic acid (5.68 g, 36.2 mmol) in EtOH (100 ml) at ambienttemperature and the mixture stirred for 48 h. The mixture was reduced in vacuaand dried through azeotrope with toluene to afford 4-nitro-lH-pyrazole-3-carboxylic acid ethyl ester as a white solid (6.42 g, 96percent). (*H NMR (400 MHz,DMSO-d6) 8 14.4 (s, 1H), 9.0 (s, 1H), 4.4 (q, 2H), 1.3 (t, 3H)).
96%	With thionyl chloride; at 20℃; for 48h;	Preparation VIII; Synthesis of 4-ammo-1H-pyrazole-3-carboxylic acid ethyl esterStep 1. 4-Nitro-1H-pyrazole-3-carboxylic acid ethyl esterThionyl chloride (2.90 ml, 39.8 mmol) was slowly added to a mixture of 4-nitro-3- pyrazolecarboxylic acid (5.68 g, 36.2 mmol) in EtOH (100 ml) at ambient temperature and the mixture stirred for 48 hours. The mixture was reduced in vacuo and dried through azeotrope with toluene to afford 4-nitro-1H-pyrazole-3- carboxylic acid ethyl ester as a white solid (6.42 g, 96percent). (1H NMR (400 MHz, DMSO-d6) delta 14.4 (s, IH), 9.0 (s, IH), 4.4 (q, 2H), 1.3 (t, 3H)).
96%	With thionyl chloride; at 20℃; for 48h;	Thionyl chloride (2.90 ml, 39.8 mmol) was slowly added to a mixture of 4-nitro-3-pyrazolecarboxylic acid (5.68 g, 36.2 mmol) in EtOH (100 ml) at ambient temperature and the mixture stirred for 48 h. The mixture was reduced in vacuo and dried through azeotrope with toluene to afford 4-nitro-1H-pyrazole-3-carboxylic acid ethyl ester as a white solid (6.42 g, 96percent). (1H NMR (400 MHz, DMSO-d6) D 14.4 (s, 1 H), 9.0 (s, 1 H), 4.4 (q, 2H), 1.3 (t, 3H)).
96%	With thionyl chloride; at 20℃; for 48h;	Thionyl chloride (2.90 ml, 39.8 mmol) was slowly added to a mixture of 4-nitro-3-pyrazolecarboxylic acid (5.68 g, 36.2 mmol) in EtOH (100 ml) at ambient temperature and the mixture stirred for 48 h. The mixture was reduced in vacuo and dried through azeotrope with toluene to afford 4-nitro-1H-pyrazole-3-carboxylic acid ethyl ester as a white solid (6.42 g, 96percent). (1H NMR (400 MHz, DMSO-d6) D 14.4 (s, 1 H), 9.0 (s, 1 H), 4.4 (q, 2H), 1.3 (t, 3H)).
96%	With thionyl chloride; at 20℃; for 48h;	Step 1. 4-Nitro-lH-pyrazole-3-carboxylic acid ethyl ester; Thionyl chloride (2.90 ml, 39.8 mmol) was slowly added to a mixture of 4-nitro-3- pyrazolecarboxylic acid (5.68 g, 36.2 mmol) in EtOH (100 ml) at ambient temperature and the mixture stirred for 48 hours. The mixture was reduced in vacuo and dried through azeotrope with toluene to afford 4-nitro-lH-pyrazole-3- carboxylic acid ethyl ester as a white solid (6.42 g, 96percent). (1H NMR (400 MHz, DMSO-d6) delta 14.4 (s, IH), 9.0 (s, IH), 4.4 (q, 2H), 1.3 (t, 3H)).
	With sulfuric acid; for 5h;Heating / reflux;	[00842] Example 209: 4- [ (Aminocarbonyl) amino]-l- (3-chloro-4- methoxyphenyl)-1 H-pyrazole-3-carboxamide; [00844] Step 1: Preparation of ethyl 4-nitro-1 H-pyrazole-3-carboxylate [00846] 4-Nitro-1 H-pyrazole-3-carboxylic acid (2 g, 12.73 mmol ; Aldrich) was refluxed in absolute ethanol (25 mL) containing trace sulfuric acid (0. 2. mol) for 5 h. The reaction was evaporated and partitioned between EtOAc and 5percent NaHCO3. The EtOAc layer was separated, dried over MgSO4 and filtered. The EtOAc was removed to give a white solid.'H. NMR (300 MHz, DMSO-d6) : 5 1.28 (t, J=7 Hz, 3 H), 4. 34 (q, J=7 Hz, 2 H), 8.91 (s, 1 H), 14.39 (br s, 1 H); MS (ESI+) for CH N 186. 1 (M+H) +.

Reference： [1]Patent: US2011/306589,2011,A1 .Location in patent: Page/Page column 45
[2]Patent: WO2011/154327,2011,A1 .Location in patent: Page/Page column 118
[3]Patent: CN108948019,2018,A .Location in patent: Paragraph 0497; 0499; 0500
[4]Patent: WO2006/70198,2006,A1 .Location in patent: Page/Page column 122-123
[5]Patent: WO2006/3440,2006,A1 .Location in patent: Page/Page column 147
[6]Patent: WO2006/77414,2006,A1 .Location in patent: Page/Page column 142
[7]Patent: WO2006/77424,2006,A1 .Location in patent: Page/Page column 186
[8]Patent: WO2006/77428,2006,A1 .Location in patent: Page/Page column 163
[9]Patent: WO2008/7123,2008,A2 .Location in patent: Page/Page column 111
[10]Journal of Medicinal Chemistry,2008,vol. 51,p. 4986 - 4999
[11]Patent: WO2005/37797,2005,A1 .Location in patent: Page/Page column 271-272

10
[ 55864-87-4 ]
[ 65190-36-5 ]

Yield	Reaction Conditions	Operation in experiment
86%	With ammonia; In water; at 90℃; for 3h;	a) Ethyl 4-NITRO-LH-PYRAZOLE-3-CARBOXYLATE (741 mg, 4 mmol) was heated at 90C with a concentrated solution of aqueous ammonia (28%, 20 ML) in a sealed vessel for 3 hours. The mixture was evaporated and the residue was triturated with diethyl ether to give 4-NITRO-LH- pyrazole-3-carboxamide (0.54 g, 86% yield) as a white solid: 1H-NMR (DMSO d6) : 8. 70 (s, 1H), 8.06 (s, 1H), 7. 83 (s, 1H); MS (+VEESI) : 157.13 (M+H) +.

Reference： [1]Patent: WO2004/94410,2004,A1 .Location in patent: Page 131

11
[ 350-81-2 ]
[ 55864-87-4 ]
ethyl 1-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-4-nitro-1H-pyrazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃; for 20h;	a) A mixture of ethyl 4-NITRO-LH-PYRAZOLE-3-CARBOXYLATE (0. 685 g, 3.7 mmol) and 2- chloro-N- (3-fluorophenyl) acetamide (0.694 g, 3.7 mmol) and potassium carbonate (0.613 g, 4.44 mmol) in dimethyl formamide (10 ml) was stirred at room temperature for 20 hours. The mixture was evaporated and the residue was purified by silica gel chromatography eluting with a 8 to 10% mixture of ethyl acetate in dichloromethane to give ethyl 1- {2- [ (3- fluorophenyl) AMINO]-2-OXOETHYL}-4-NITRO-LH-PYRAZOLE-3-CARBOXYLATE (0.920 g, 74% yield): H-NMR (DMSO d6 TFA): 9.02 (s, 1H), 7.57 (d, 1H), 7.39 (q, 1H), 7.32 (d, 1H), 6.93 (t, 1H), 5.24 (s, 2H), 4.38 (q, 2H), 1.31 (t, 3H); MS (+ ve ESI): 337.17 (M+H) +.

Reference： [1]Patent: WO2004/94410,2004,A1 .Location in patent: Page 132

12
[ 75-36-5 ]
[ 5334-40-7 ]
[ 55864-87-4 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol; at 0 - 20℃; for 48.5h;	Step 1. Preparation of 4-Nitro-1H-pyrazole-3-carboxylic acid, ethyl ester. Acetyl chloride (50 mL) was added dropwise to ethanol (450 mL) at 0° C. with stirring. After addition was complete, the ice-bath was removed, and the mixture was stirred at room temperature for 30 minutes. To this mixture was added 4-nitro-1H-pyrazole-3-carboxylic acid (Aldrich) (10 g, 63.65 mmol), and the resulting homogeneous mixture was stirred at room temperature for a total of 48 hours. The reaction was monitored by TLC. The solvent was removed under reduced pressure and then co-evaporated with ethyl acetate four times. The residue was concentrated under high vacuum to give the title compound as a white powder (11.426 g, (M-H)+=184, M.P.=128.0-130.1° C.).

Reference： [1]Patent: US2005/197340,2005,A1 .Location in patent: Page/Page column 68

13
[ 5334-40-7 ]
[ 55864-87-4 ]

Yield	Reaction Conditions	Operation in experiment
96%	With thionyl chloride; In ethanol; at 20℃; for 48h;	Thionyl chloride (2.90 ml, 39.8 mmol) was slowly added to a mixture of 4-nitro-3- pyrazolecarboxylic acid (5.68 g, 36.2 mmol) in EtOH (100 ml) at ambient temperature and the mixture stirred for 48 h.The mixture was reduced in vacuo and dried through azeotrope with toluene to afford 4-nitro-1H-pyrazole-3-carboxylic acid ethyl ester as a white solid (6.42 g, 96percent). (1H NMR (400 MHz, DMSO-d6) delta 14.4 (s, 1H), 9.0 (s, 1H), 4.4 (q, 2H), 1.3 (t, 3H)).
		Example 17: Synthesis of 3-(2-chloro-phenyl)-6-(2,4-difluoro-phenoxy)-4-methyl-l,4- dihydro-pyrazolo[4,3-b]pyridin-5-one following the procedure of SchemeII; Step 1. Preparation of 4-Nitro-lH-pyrazole-3-carboxylic add, ethyl ester.; Acetyl chloride (50 mL) was added dropwise to ethanol (450 mL) at 00C with stirring. After addition was complete, the ice-bath was removed, and the mixture was stirred at RT for 30 min. To this mixture was added 4-nitro-lH-pyrazole-3-carboxylic acid (10 g, 63.65 mmol), and the resulting homogeneous mixture was stirred at RT for a total of 48 hours. EPO <DP n="65"/>The reaction was monitored by TLC. The solvent was removed under reduced pressure and then co-evaporated with ethyl acetate four times. The residue was concentrated under high vacuum to give the title compound as a white powder (11.426 g, (M-H)+ =184, M.P.= 128.0- 130.1 0C).

Reference： [1]Patent: WO2005/12256,2005,A1 .Location in patent: Page/Page column 184
[2]Patent: WO2007/23105,2007,A1 .Location in patent: Page/Page column 63-64

14
[ 55864-87-4 ]
[ 824-94-2 ]
[ 825619-24-7 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In acetonitrile; at 20℃; for 20h;	To a solution of 4-nitro-lH-pyrazole-3-carboxylic acid ethyl ester (Example 3A, 8.8 g, 47.5 mmol) in MeCN (100 ml) was added K2CO3 (7.9 g, 57.0 mmol) followed by 4-methoxybenzyl chloride (7.1 ml, 52.3 mmol) and the mixture stirred at ambient temperature for 20 hours. The mixture was evaporated in vacuo, the residue EPO <DP n="170"/>partitioned between EtOAc and 2M aqueous hydrochloric acid and the organic portion washed with saturated aqueous sodium hydrogen carbonate, dried (MgSO4) and evaporated in vacuo. The residue was purified by flash column chromatography [SiO2, EtOAc-hexane (1:4)] to give l-(4-methoxy-benzyl)-4-nitro-lH-pyrazole-3- carboxylic acid ethyl ester (11 g) as a colourless gum.

Reference： [1]Patent: WO2006/70198,2006,A1 .Location in patent: Page/Page column 168-169

15
[ 76513-69-4 ]
[ 55864-87-4 ]
[ 864300-88-9 ]
[ 864300-87-8 ]

Yield	Reaction Conditions	Operation in experiment
		Step 2. Preparation of 4-nitro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazole-3-carboxylic acid, ethyl ester and 4-nitro-2-(2-trimethylsilanyl-ethoxymethyl)-2H-pyrazole-3-carboxylic acid, ethyl ester. To a 0 C. solution of <strong>[55864-87-4]4-nitro-1H-pyrazole-3-carboxylic acid ethyl ester</strong> (6.4 g, 34.58 mmol) in dimethylformamide (80 mL) was added sodium hydride (2.07 g, 1.5 eq), and the resulting mixture was stirred from 0 C. to room temperature for one hour. To this mixture was added 2-(trimethylsilyl)ethoxy-methyl chloride (Aldrich) (9.17 mL, 1.5 eq), and the resulting mixture was stirred at room temperature for 2 days. The reaction was monitored by TLC. The reaction mixture was diluted with ethyl acetate (300 mL) and water (100 mL). the organic layer was separated, washed with water (6100 mL) and brine (1100 mL), dried over magnesium sulfate, filtered and concentrated to give 10 g of the crude product. Purification by column chromatography using 5% ethyl acetate in hexanes afforded 4-nitro-2-(2-trimethylsilanyl-ethoxymethyl)-2H-pyrazole-3-carboxylic acid, ethyl ester (3.82 g) as a colorless oil and 4-nitro-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazole-3-carboxylic acid, ethyl ester (4.055 g) as a light tan oil. (M-H)+=314.

Reference： [1]Patent: US2005/197340,2005,A1 .Location in patent: Page/Page column 68-69

17
[ 55864-87-4 ]
[ 6482-24-2 ]
[ 1352199-83-7 ]
[ 1352199-80-4 ]

Yield	Reaction Conditions	Operation in experiment
25%; 55%		To a solution of <strong>[55864-87-4]4-nitro-1H-pyrazole-3-carboxylic acid ethyl ester</strong> (100 mg, 0.54 mmol) in DMSO (1 mL) was added potassium carbonate (164 mg, 1.19 mmol) and the reaction mixture was stirred for 5 min. 1-Bromo-2-methoxyethane (110 mul, 1.19 mml) was added and the resulting reaction mixture was stirred at ambient temperature overnight. The reaction mixture was partitioned between ethyl acetate and water and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried and the solvent was evaporated. The product was obtained as a mixture of regioisomers which were separated by silica gel chromatography using a heptane /ethyl acetate gradient to yield 72 mg (55%) of the desired regioisomer and 33 mg (25%) of 2-(2-methoxyethyl)-4-nitro-2H-pyrazole-3-carboxylic acid ethyl ester. MS: M=244.3 (M+H)+
25%; 55%		To a solution of 4-nitro-lH-pyrazole-3-carboxylic acid ethyl ester (100 mg, 0.54 mmol) in DMSO ( 1 mL) was added potassium carbonate (164 mg, 1.19 mmol) and the reaction mixture was stirred for 5 min. l-Bromo-2-methoxyethane (110 mu, 1.19 mml) was added and the resulting reaction mixture was stirred at ambient temperature overnight. The reaction mixture was partitioned between ethyl acetate and water and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried and the solvent was evaporated. The product was obtained as a mixture of regioisomers which were separated by silica gel chromatography using a heptane/ethyl acetate gradient to yield 72 mg (55 %) of the desired regioisomer and 33 mg (25 %) of 2-(2-methoxyethyl)-4-nitro-2H-pyrazole-3-carboxylic acid ethyl ester.MS: M = 244.3 (M+H)+

Reference： [1]Patent: US2011/306589,2011,A1 .Location in patent: Page/Page column 45
[2]Patent: WO2011/154327,2011,A1 .Location in patent: Page/Page column 118-120

18
[ 55864-87-4 ]
[ 13035-61-5 ]
[ 55864-81-8 ]

Reference： [1]Chemical Science,2016,vol. 7,p. 995 - 1010

19
[ 55864-87-4 ]
[ 13035-61-5 ]
ethyl 4-amino-1-(2,3,5-O-triacetyl-β-D-ribofuranosyl)-1H-pyrazole-3-carboxylate [ No CAS ]

Reference： [1]Chemical Science,2016,vol. 7,p. 995 - 1010

20
[ 55864-87-4 ]
ethyl 4-amino-1-methylpyrazole-3-carboxylate [ No CAS ]

Reference： [1]Patent: WO2015/193168,A1
Patent: ,2015,

21
[ 55864-87-4 ]
[ 74-88-4 ]
[ 378203-86-2 ]

Yield	Reaction Conditions	Operation in experiment
60.9%	With potassium carbonate; In acetonitrile;	INTERMEDIATE 12 Ethyl 1 -methyl-4-nitropyrazole-3 -carboxylate lodomethane (0.75 mL, 12 mmol) was added to a suspension of ethyl 4-nitro-1H- pyrazole-3-carboxylate (2 g, 10.80 mmol) and potassium carbonate (2.24 g, 16.2 mmol) in acetonitrile (50 mL). The reaction mixture was stirred overnight, then concentrated in vacuo. The residue was partitioned between DCM and brine, then separated. The organiclayer was passed through a phase separator cartridge, then evaporated. The resulting crude material was purified by silica gel chromatography (gradient 5-30% EtOAc in isohexane). The title compound (1.31 g, 60.9%) was obtained as a white solid. oH (400 MHz, DMSO-d6) 8.94 (s, 1H), 4.36 (q, 2H,J7.1 Hz), 3.95 (s, 3H), 1.30 (t, 3H,J7.1 Hz).

Reference： [1]Patent: WO2015/193168,A1 .Location in patent: Page/Page column 54
Patent: ,2015, .Location in patent: Page/Page column 54

22
[ 55864-87-4 ]
[ 74-88-4 ]
ethyl 1-methyl-4-nitro-1H-pyrazole-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 12h;	Ethyl 4-nitro-lH-pyrazole-3-carboxylate (1.5 g, 8.10 mmol) and K2C03 (2.2 g, 16.20 mmol) were stirred in DMF (15.0 ml). To the mixture was added iodomethane (1.201 g, 8.51 mmol). The reaction mixture was stirred at room temperature for 12 hours. The reaction mixture was poured into EtOAc/brine. The organic layer was washed with brine three times, dried over MgS04 and evaporated. The resulting material was purified by flash chromatography on silica eluting with 5% to 80% EtOAc/hexane to afford the title compound (non-polar fractions) (638 mg, yield: 40%). The polar fractions afforded ethyl l-methyl-4-nitro-lH-pyrazole-3- carboxylate. The regioisomers were assigned based on the reported NMR shift (WO2012073143(Al)). 1H-NMR (400 MHz, CDC13) delta 1.42 (t, 3 H) 1.55 (s, 1 H) 4.01 (s, 3 H) 4.47 (q, 2 H) 8.13 (s, 1 H)

Reference： [1]Patent: WO2016/164703,2016,A1 .Location in patent: Page/Page column 67

23
[ 55864-87-4 ]
ethyl 4-amino-1-(pyridin-3-yl)-1H-pyrazole-3-carboxylate [ No CAS ]

Reference： [1]Patent: WO2016/144844,2016,A1

24
[ 1692-25-7 ]
[ 55864-87-4 ]
ethyl 4-nitro-1-(pyridin-3-yl)-1H-pyrazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; copper diacetate; In N,N-dimethyl-formamide; at 80℃; for 5h;	Into a 1 L round-bottom flask were placed ethyl 4-nitro-7H-pyrazole-3 -carboxylate (15 g, 81 mmol), (pyridin-3-yl)boronic acid (10 g, 81 mmol) and copper(II) acetate (15 g, 83 mmol) in NN-dimethylformamide (400 mL). This was followed by the addition of pyridine (6.4 g, 81 mmol) dropwise with stirring at room temperature. The resulting solution was stirred for 5 h at 80 C in an oil bath, then concentrated under vacuum. The residue was purified by flash chromatography on silica gel, eluting with a mixture of 5% MeOH in CH2CI2. This resulted in ethyl 4-nitro-l-(pyridin-3-yl)-7H-pyrazole-3-carboxylate as an oil. MS [M+H]+ 263.

Reference： [1]Patent: WO2016/144844,2016,A1 .Location in patent: Page/Page column 31

25
[ 55864-87-4 ]
[ 23735-43-5 ]
(R)-ethyl 1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-4-nitro-1H-pyrazole-3-carboxylate [ No CAS ]
(R)-ethyl 1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-4-nitro-1H-pyrazole-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 12h;	Ethyl 4-nitro-lH-pyrazole-3-carboxylate (620 mg, 3.349 mmol), (S)-(2,2-dimethyl-l,3-dioxolan- 4-yl)methyl 4-methylbenzenesulfonate (1055 mg, 3.684 mmol) and K2C03 (926 mg, 6.698 mmol) were stirred in DMF (5.0 ml). The reaction mixture was stirred at 80 C for 12 hours. The reaction mixture was poured into EtO Ac/brine. The organic layer was washed with brine three times, dried over MgS04 and evaporated. The remaining material was purified by flash chromatography on silica eluting with 0% to 40% EtOAc/Hexane to afford the title compound (polar fractions) (503 mg, yield: 52%). The non-polar fractions afforded (R)-ethyl l-((2,2- dimethyl- 1 ,3 -dioxolan-4-yl)methyl)-4-nitro- 1 H-pyrazole-5-carboxylate. 1H-NMR (400 MHz, CDC13) delta 1.35 - 1.45 (m, 9 H) 3.76 (dd, 1 H) 4.10 - 4.27 (m, 2 H) 4.33 - 4.41 (m, 1 H) 4.44 - 4.52 (m, 3 H) 8.28 (s, 1 H)

Reference： [1]Patent: WO2016/164754,2016,A1 .Location in patent: Page/Page column 49

26
[ 55864-87-4 ]
[ 74-88-4 ]
ethyl 1-methyl-4-nitro-1H-pyrazole-5-carboxylate [ No CAS ]
[ 378203-86-2 ]

Yield	Reaction Conditions	Operation in experiment
40%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 12h;	Ethyl 4-nitro-lH-pyrazole-3-carboxylate (1.5 g, 8.10 mmol) and K2C03 (2.2 g, 16.20 mmol) were stirred in DMF (15.0 ml). To the mixture was added iodomethane (1.201 g, 8.51 mmol). The reaction mixture was stirred at room temperature for 12 hours. The reaction mixture was poured into EtO Ac/brine. The organic layer was washed with brine three times, dried over MgS04 and evaporated. The resulting material was purified by flash chromatography on silica eluting with 5% to 80% EtOAc/Hexane to afford the title compound (non-polar fractions) (638 vmg, yield: 40%). The polar fractions afforded ethyl l-methyl-4-nitro-lH-pyrazole-3- carboxylate. The regioisomers were assigned based on the reported NMR shift (WO2012073143(Al)). 1H-NMR (400 MHz, CDC13) delta 1.42 (t, 3 H) 1.55 (s, 1 H) 4.01 (s, 3 H) 4.47 (q, 2 H) 8.13 (s, 1 H)

Reference： [1]Patent: WO2016/164754,2016,A1 .Location in patent: Page/Page column 38; 39

27
3-chloro-6-(chloromethyl)quinoline [ No CAS ]
[ 55864-87-4 ]
1-(3-chloroquinolin-6-ylmethyl)-4-nitro-1H-pyrazole-3-carboxylic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	A mixture of 4-nitro-lH-pyrazole-3-carboxylic acid ethyl ester (1.0 g, 5.40 mmol, 1.0 eq), 3-chloro-6-chloromethyl-quinoline (1.37 g, 6.49 mmol, 1.2 eq) and K2C03 (1.49 g, 10.8 mmol, 2.0 eq) in DMF (20 mL) was stirred at rt overnight. The mixture was concentrated, and the resulting residue was diluted with water. The mixture was extracted with EtOAc. The combined organic layers were dried and concentrated. The resulting residue was purified by chromatography on silica gel column (DCM/MeOH = 40/1, v/v) to give l-(3-chloro-quinolin-6-ylmethyl)-4-nitro-lH-pyrazole-3-carboxylic acid ethyl ester (1.68 g, 86%).

Reference： [1]Patent: WO2018/11628,2018,A1 .Location in patent: Paragraph 00239

28
[ 55864-87-4 ]
[ 106-93-4 ]
1-(2-bromoethyl)-4-nitro-1H-pyrazole-5-carboxylic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
27%	With potassium carbonate; In acetone; at 40℃; for 4h;	Add <strong>[55864-87-4]4-nitro-1H-pyrazole-3-carboxylic acid ethyl ester</strong> (3.00 g, 16.2 mmol) in a 100 mL vial, 60 mL of acetone and potassium carbonate solid (11.2 g, 81.0 mmol).1,2-dibromoethane (4.21 mL, 48.6 mmol) was added in one portion at room temperature, and the reaction was heated in an oil bath at 40 C for 4 h. The reaction was completed by TLC, cooled to room temperature, filtered, and washed with 30 mL of EA. Cake, willThe filtrate was spin-dried on silica gel column chromatography eluting with PE/EA=40/1 to 5/1, 1.17g of light yellow oil, yield 27%,

Reference： [1]Patent: CN108948019,2018,A .Location in patent: Paragraph 0497; 0501; 0502

29
[ 55864-87-4 ]
[ 223463-14-7 ]
ethyl 1-(6-bromo-3-pyridyl)-4-nitropyrazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21%	With pyridine; oxygen; copper diacetate; In dichloromethane; at 20℃; under 775.743 Torr; for 16h;	To a solution of ethyl 4-nitro-1H-pyrazole-3-carboxylate (5.8 g, 31.3 mmol, CAS55864-87-4), pyridine (9.91 g, 125 mmol) and Cu(OAc)2 (8.54 g, 46.9 mmol) in DCM (120 mL) was added <strong>[223463-14-7](6-bromo-3-pyridyl)boronic acid</strong> (7.59 g, 37.5 mmol, CAS223463-14-7). The mixture was stirred at rt for 16 hours under an oxygen atmosphere (15 psi pressure). On completion, the reaction mixture was quenched by adding saturated NH3.H2O solution (40 mL). The organic layer was separated and dried over Na2SO4, filtered and concentrated in vacuo to give a residue. The residue was purified by silica gel chromatography (PE/EA=3/1) to give the title compound (2.30 g, 21% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) delta 9.83 (s, 1H), 9.00 (d, J=2.8 Hz, 1H), 8.31 (dd, J=3.2, 8.8 Hz, 1H), 7.91 (d, J=8.8 Hz, 1H), 4.42 (q, J=7.2 Hz, 2H), 1.33 (t, J=7.2 Hz, 3H).

Reference： [1]Patent: US2019/192668,2019,A1 .Location in patent: Paragraph 2534; 2535

30
[ 107-08-4 ]
[ 55864-87-4 ]
C₉H₁₃N₃O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62.4%	With potassium carbonate; In acetonitrile; at 60 - 70℃; for 16h;	To a mixture of compound A32 (12.4 g, 66.9 mmol, 1 eq) and K2CO3 (23.1 g, 167 mmol, 2.5 eq) in MeCN (120 mL) was added Dl-1 (28.5 g, 167 mmol, 16.4 mL, 2.5 eq) and the resulting mixture was heated to 60-70C for 16 hours to afford a white mixture. TLC showed two new spots. The mixture was partitioned between EtOAc (100 mL) and H20 (100 mL). The aqueous phase was extracted with EtOAc (100 mL x 2). The combined organic extract was dried over anhydrous Na2S04, filtered and concentrated under reduced pressure to give crude product. The crude product was purified by combi flash (PE/EtOAc = 1/0 to 4/1 to 3/1) to afford compound A33 (9.5 g, 62.4% yield) as a yellow oil.

Reference： [1]Patent: WO2019/229251,2019,A1 .Location in patent: Page/Page column 64-65

31
[ 55864-87-4 ]
4-amino-5-ethoxycarbonyl-2-(tetrahydropyran-2-yl)-pyrazole [ No CAS ]