Name: 167408-67-5|Methyl 4-Cyclopropyl-2,4-dioxobutanoate|95%
Brand: Ambeed
SKU: A173000
Price: 26.0 USD
Availability: InStock
Rating: 97 (25 reviews)

1
[ 553-90-2 ]
[ 765-43-5 ]
[ 167408-67-5 ]

Yield	Reaction Conditions	Operation in experiment
55%	Stage #1: Dimethyl oxalate; Cyclopropyl methyl ketone With methanol; natrium at 0 - 20℃; Reflux; Stage #2: With sulfuric acid In diethyl ether; lithium hydroxide monohydrate	Synthesis of compound 1 Na (14.67g, 0.64mol) was dissolved in dry MeOH (0.8L) and a solution of cyclo- propylmethylketone (50g, 0.59mol) and dimethyloxalate (70.2g, 0.59mol) in dry MeOH (0.2L) was added dropwise at 0°C. The reaction mixture was stirred at r.t. 24h and reflux overnight. Water (0.5L) was added and the methanol was removed under reduced pressure. The aqueous solution was washed with Et21H-NMR (CDCI3): δ= 14.61 (br, 1 H), 6.84 (s, 1 H), 3.90 (s, 3H), 1 .95-1 .82 (m, 1 H), 1.26- 1 .20 (m, 2H), 1 .10-1 .00 (m, 2H).
55%	With methanol; natrium at 0 - 20℃; Reflux; Inert atmosphere;	Synthesis of compound 10 Na (14.67 g, 0.64 mol) was dissolved in dry methanol (0.8 L) and a solution of cyclopropylmethylketone 5 (50 g, 0.59 mol) and dimethyloxalate (70.2 g, 0.59 mol) in dry MeOH (0.2 L) was added dropwise at 0°C. The reaction mixture was stirred at room temperature 24h and reflux overnight. Water (0.5 L) was added and the methanol was removed under reduced pressure. The aqueous solution was washed with Et.20 (150 ml_), acidified to pH=2 with 2M H2S04 and extracted with Et20 (diethylether, 3x150 ml_). The organic layer was dried over MgS04 and concentrated to dryness, to yield compound 10 (55.6 g, 55%), which was used without further purification. H-NMR (CDCIs): δ= 14.61 (br, 1 H), 6.84 (s, 1 H), 3.90 (s, 3H), 1 .95-1 .82 (m, 1 H), 1 .26- 1 .20 (m, 2H), 1 .10-1 .00 (m, 2H).
5 g	Stage #1: Cyclopropyl methyl ketone With sodium methoxide In methanol at 20℃; for 0.25h; Stage #2: Dimethyl oxalate In methanol at 20℃; for 16h;	O1 -Cvclopropyl-2,4-dioxo-butyric acid methyl ester To a solution of cyclopropyl methyl ketone (5 g, 59.4 mmol) in MeOH (75 ml.) was added sodium methoxide (4.8 g, 54.0 mmol) at rt. After a 15 min stirring, dimethyl oxalate (7 g, 59.4 mmol) was added. The reaction mixture was stirred for 16 h at rt and concentrated. The residue was taken up in a saturated aqueous solution of ammonium chloride and extracted with EtOAc. The organic layers were dried (Na2S04), filtered, and concentrated. The residue was purified by silica gel column chromatography (hexane/EtOAc, 95:5) to provide 5 g of the title compound. Rf= 0.59 (hexane/EtOAc, 4:1 ); H NMR (300 MHz, CDCI3) δ ppm 1.00-1.30 (m, 4 H), 1.80-1.95 (m, 1 H), 3.85 (s, 3 H), 6.48 (s, 1 H), 14.2-15.0 (br. s, 1 H).

	With potassium-t-butoxide In tetrahydrofuran; toluene at 20℃;
	With sodium methoxide In methanol at 0 - 20℃; for 12h; Inert atmosphere;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 1. To a solution of acetone (6a, 580 mg, 10 mmol) and dimethyloxalate (7, 1.18 g, 10 mmol) in anhydrous methanol (50 mL) was degassed with argon and cooled to 0 °C in an ice bath. 30% sodium methanolate in methanol (20 mmol) was added dropwise into the coldsolution and the mixture was allowed to warm to room temperature. After 12 h, the resultant mixture was quenched with conc. HCl (5 mL)and concentrated in vacuo. The residue was then diluted with water (50 mL) and extracted with EA (50 mL). The organic phase was separated, dried over anhydrous sodium sulfate, filtered and concentrated to give methyl acetopyruvate (8a) which was directly used in the next step without further purification.
	With sodium methoxide In methanol at 0 - 20℃; for 12h; Inert atmosphere;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 1. To a solution of acetone (6a, 580 mg, 10 mmol) and dimethyloxalate (7, 1.18 g, 10 mmol) in anhydrous methanol (50 mL) was degassed with argon and cooled to 0 °C in an ice bath. 30% sodium methanolate in methanol (20 mmol) was added dropwise into the coldsolution and the mixture was allowed to warm to room temperature. After 12 h, the resultant mixture was quenched with conc. HCl (5 mL)and concentrated in vacuo. The residue was then diluted with water (50 mL) and extracted with EA (50 mL). The organic phase was separated, dried over anhydrous sodium sulfate, filtered and concentrated to give methyl acetopyruvate (8a) which was directly used in the next step without further purification.

Reference： [1]Current Patent Assignee: BASF SE - WO2012/10633, 2012, A1 Location in patent: Page/Page column 53
[2]Current Patent Assignee: BASF SE - WO2013/104561, 2013, A1 Location in patent: Page/Page column 49
[3]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2013/80141, 2013, A1 Location in patent: Page/Page column 94
[4]Ye, Jiqing; Lin, Lin; Xu, Jinyi; Chan, Paul Kay-Sheung; Yang, Xiao; Ma, Cong [Pharmaceuticals, 2021, vol. 14, # 4]
[5]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[6]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

2
[ 14678-02-5 ]
[ 167408-67-5 ]
[ 931997-41-0 ]

Yield	Reaction Conditions	Operation in experiment
97%	With acetic acid for 2h; Reflux;	Synthesis of compound 4A mixture of compound 1 (3g, 17.6mmol) and 5-amino-3-methylisoxazole (1 .73g, 17.6mmol) in AcOH (44mL) was stirred at reflux for 2h. The reaction mixture was poured into ice/water (100ml_). The solid formed was collected by filtration and dried under high vacuum. 3.9g (97%) of compound 4 were obtained.1H-NMR (CDCI3): δ= 7.69 (s, 1 H), 4.02 (s, 3H), 2.69 (s, 3H), 2.26-2.15 (m, 1 H), 1 .28- 1 .21 (m, 2H), 1 .19-1 .1 1 (m, 2H).MS: m/z= 233 [M+H]+

Reference： [1]Current Patent Assignee: BASF SE - WO2012/10633, 2012, A1 Location in patent: Page/Page column 54

3
[ 167408-67-5 ]
[ 822-63-9 ]
[ 1356475-42-7 ]

Yield	Reaction Conditions	Operation in experiment
82%	With acetic acid for 2h; Reflux;	Synthesis of compound 20 A mixture of compound 1 (17g, 0.1 mol) and 5-amino-isoxazol-3-one (10g,0.1 mol) in acetic acid (AcOH) (100ml_) was stirred at reflux for 2h. The reaction mixture was poured into ice/water (200ml_). The solid formed was collected by filtration and dried under high vacuum. 19g (82%) of compound 20 were obtained.1H-NMR (CDCI3): δ= 10.30 (bs, 1 H), 7.69 (s, 1 H), 4.12 (s, 3H), 2.27-2.20 (m, 1 H), 1.29- 1 .22 (m, 2H), 1 .21 -1 .12 (m, 2H).MS: m/z= 235 [M+H]+
82%	With acetic acid for 2h; Reflux;	Synthesis of compound 11 A mixture of compound 10 (17 g, 0.1 mol) and 5-amino-isoxazol-3-one (10 g, 0.1 mol) in acetic acid (AcOH) (100 ml.) was stirred at reflux for 2h. The reaction mixture was poured into ice/water (200 ml_). The solid formed was collected by filtration and dried under high vacuum. 19 g (82%) of compound 11 were obtained. H-NMR (CDCIs): δ= 10.30 (bs, 1 H), 7.69 (s, 1 H), 4.12 (s, 3H), 2.27-2.20 (m, 1 H), 1 .29- 1 .22 (m, 2H), 1 .21 -1.12 (m, 2H); MS: m/z= 235 [M+H]+

Reference： [1]Current Patent Assignee: BASF SE - WO2012/10633, 2012, A1 Location in patent: Page/Page column 60
[2]Current Patent Assignee: BASF SE - WO2013/104561, 2013, A1 Location in patent: Page/Page column 50

4
[ 167408-67-5 ]
[ 1356475-44-9 ]
[ 1356475-45-0 ]

Yield	Reaction Conditions	Operation in experiment
72%	With acetic acid for 2h; Reflux;	Synthesis of compound 27A mixture of compound 1 (1 1 .5g, 0.07mol) and 26 (13.8g, 0.07mol) in AcOH (150ml_) was stirred at reflux for 2h. The reaction mixture was poured into ice/water (200ml_). The solid formed was collected by filtration and dried under high vacuum. 16.5g (72%) of compound 27 were obtained.1H-NMR (CDCb): δ= 7.68 (s, 1 H), 7.32 (s, 5H), 5.03 (s, 2H), 4.60 (s, 2H), 3.95 (s, 3H), 2.26-2.20 (m, 1 H), 1 .30-1.25 (m, 2H), 1 .20-1 .12 (m, 2H).MS: m/z= 339 [M+H]+
72%	With acetic acid for 2h; Reflux;	Synthesis of compound 26 A mixture of compound 10 (1 1.5 g, 0.07 mol) and 25 (13.8 g, 0.07 mol) in AcOH (150 ml.) was stirred at reflux for 2h. The reaction mixture was poured into ice/water (200 ml_). The solid formed was collected by filtration and dried under high vacuum. 16.5 g (72%) of compound 26 were obtained. H-NMR (CDCIs): δ= 7.68 (s, 1 H), 7.32 (s, 5H), 5.03 (s, 2H), 4.60 (s, 2H), 3.95 (s, 3H), 2.26-2.20 (m, 1 H), 1 .30-1.25 (m, 2H), 1 .20-1 .12 (m, 2H); MS: m/z= 339 [M+H]+

Reference： [1]Current Patent Assignee: BASF SE - WO2012/10633, 2012, A1 Location in patent: Page/Page column 62
[2]Current Patent Assignee: BASF SE - WO2013/104561, 2013, A1 Location in patent: Page/Page column 55

5
[ 167408-67-5 ]
[ 119162-59-3 ]
[ 1356473-94-3 ]

Yield	Reaction Conditions	Operation in experiment
79%	With acetic acid for 4h; Reflux;	Synthesis of compound 2 A mixture of compound 1 (0.9g, 5.3mmol) and 5-amino-3-(2- phenylethyl)isoxazole (1.0g, 5.3mmol) in AcOH (16ml_) was stirred at reflux for 4h. The reaction mixture was poured into ice/water (100ml_). The solid formed was collected by filtration and dried under high vacuum. 1.5g (79%) of compound 2 were obtained.1H-NMR (CDCI3): δ= 7.62 (s, 1 H), 7.27-7.1 1 (m, 5H), 3.93 (s, 3H), 3.43-3.37 (m, 2H) 3.03-2.97 (m, 2H), 2.22-2.10 (m, 1 H), 1 .24-1 .17 (m, 2H), 1 .13-1 .05 (m, 2H).MS: m/z= 323[M+H]+, 345 [M+Na]+

Reference： [1]Current Patent Assignee: BASF SE - WO2012/10633, 2012, A1 Location in patent: Page/Page column 53

6
[ 167408-67-5 ]
[ 100-52-7 ]
[ 74-89-5 ]
C₁₅H₁₅NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester; benzaldehyde; methylamine With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

7
[ 167408-67-5 ]
[ 104-88-1 ]
[ 75-04-7 ]
C₁₆H₁₆ClNO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester; 4-chlorobenzaldehyde; ethylamine With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

8
[ 167408-67-5 ]
[ 123-11-5 ]
[ 1003-03-8 ]
C₂₀H₂₃NO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester; 4-methoxy-benzaldehyde; Cyclopentamine With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

9
[ 167408-67-5 ]
[ 10031-82-0 ]
[ 108-91-8 ]
C₂₂H₂₇NO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester; 4-ethoxybenzaldehyde; cyclohexylamine With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

10
[ 498-62-4 ]
[ 167408-67-5 ]
[ 109-85-3 ]
C₁₅H₁₇NO₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-thiophene carboxaldehyde; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester; 2-methoxyethylamine With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

11
[ 498-62-4 ]
[ 167408-67-5 ]
[ 100-36-7 ]
C₁₈H₂₄N₂O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-thiophene carboxaldehyde; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester; N,N-diethylethylenediamine With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

12
[ 2038-03-1 ]
[ 498-62-4 ]
[ 167408-67-5 ]
C₁₈H₂₂N₂O₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-(2-AMINOETHYL)MORPHOLINE; 3-thiophene carboxaldehyde; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

13
[ 498-62-4 ]
[ 3731-52-0 ]
[ 167408-67-5 ]
C₁₈H₁₆N₂O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-thiophene carboxaldehyde; 3-Aminomethylpyridine; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

14
[ 498-62-4 ]
[ 5036-48-6 ]
[ 167408-67-5 ]
C₁₈H₁₉N₃O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-thiophene carboxaldehyde; 3-(1H-imidazol-1-yl)propan-1-amine; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

15
[ 140-31-8 ]
[ 498-62-4 ]
[ 167408-67-5 ]
C₁₈H₂₃N₃O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: aminoethylpiperazine; 3-thiophene carboxaldehyde; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

16
[ 498-62-4 ]
[ 167408-67-5 ]
[ 98-16-8 ]
C₁₈H₁₆N₂O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-thiophene carboxaldehyde; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester; 3-trifluoromethylaniline With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

17
[ 498-62-4 ]
[ 6336-68-1 ]
[ 167408-67-5 ]
C₂₃H₂₄N₂O₅S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-thiophene carboxaldehyde; 4-(piperidin-1-ylsulfonyl)aniline; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

18
[ 504-29-0 ]
[ 498-62-4 ]
[ 167408-67-5 ]
C₁₇H₁₄N₂O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-aminopyridine; 3-thiophene carboxaldehyde; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

19
[ 498-62-4 ]
[ 109-12-6 ]
[ 167408-67-5 ]
C₁₆H₁₃N₃O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-thiophene carboxaldehyde; 2-aminopyrimidine; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

20
[ 498-62-4 ]
[ 5049-61-6 ]
[ 167408-67-5 ]
C₁₆H₁₃N₃O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-thiophene carboxaldehyde; 2-Aminopyrazine; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

21
[ 498-62-4 ]
[ 3829-80-9 ]
[ 167408-67-5 ]
C₁₈H₁₆N₂O₅S₂ [ No CAS ]

Reference： [1]ACS Combinatorial Science,2012,vol. 14,p. 631 - 635

22
[ 498-62-4 ]
[ 28466-21-9 ]
[ 167408-67-5 ]
C₁₈H₁₉N₃O₃S [ No CAS ]

Reference： [1]ACS Combinatorial Science,2012,vol. 14,p. 631 - 635

23
[ 498-62-4 ]
[ 1072-67-9 ]
[ 167408-67-5 ]
C₁₆H₁₄N₂O₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-thiophene carboxaldehyde; 5-methylisoxazol-3-ylamine; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

24
[ 96-50-4 ]
[ 498-62-4 ]
[ 167408-67-5 ]
C₁₅H₁₂N₂O₃S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-thiazolylamine; 3-thiophene carboxaldehyde; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

25
[ 498-62-4 ]
[ 2289-75-0 ]
[ 167408-67-5 ]
C₁₇H₁₆N₂O₃S₂ [ No CAS ]

Reference： [1]ACS Combinatorial Science,2012,vol. 14,p. 631 - 635

26
[ 498-62-4 ]
[ 2536-91-6 ]
[ 167408-67-5 ]
C₂₀H₁₆N₂O₃S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-thiophene carboxaldehyde; 6-methylbenzothiazol-2-ylamine; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

27
[ 498-62-4 ]
[ 17647-70-0 ]
[ 167408-67-5 ]
C₁₅H₁₃N₃O₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-thiophene carboxaldehyde; 3-amino-4-methylfurazan; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

28
[ 498-62-4 ]
[ 108-33-8 ]
[ 167408-67-5 ]
C₁₅H₁₃N₃O₃S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-thiophene carboxaldehyde; 5-methyl-1,3,4-thiadiazol-2-amine; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

29
[ 498-62-4 ]
[ 6913-13-9 ]
[ 167408-67-5 ]
C₁₅H₁₃N₃O₃S₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-thiophene carboxaldehyde; 5-amino-3-methylthio-1,2,4-thiadiazole; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

30
[ 498-62-4 ]
[ 167408-67-5 ]
[ 150-13-0 ]
C₁₉H₁₅NO₅S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-thiophene carboxaldehyde; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester; 4-amino-benzoic acid With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

31
[ 498-62-4 ]
[ 1197-55-3 ]
[ 167408-67-5 ]
[ 1050952-63-0 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-thiophene carboxaldehyde; 4-aminophenylacetic acid; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

32
[ 498-62-4 ]
[ 93-85-6 ]
[ 167408-67-5 ]
[ 1051082-87-1 ]

Reference： [1]ACS Combinatorial Science,2012,vol. 14,p. 631 - 635

33
[ 25016-11-9 ]
[ 167408-67-5 ]
[ 74-89-5 ]
C₁₃H₁₅N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-methylpyrazole-4-carbaldehyde; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester; methylamine With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

34
[ 25016-11-9 ]
[ 167408-67-5 ]
[ 75-04-7 ]
C₁₄H₁₇N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-methylpyrazole-4-carbaldehyde; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester; ethylamine With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

35
[ 25016-11-9 ]
[ 167408-67-5 ]
[ 1003-03-8 ]
C₁₇H₂₁N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-methylpyrazole-4-carbaldehyde; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester; Cyclopentamine With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

36
[ 25016-11-9 ]
[ 167408-67-5 ]
[ 108-91-8 ]
C₁₈H₂₃N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-methylpyrazole-4-carbaldehyde; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester; cyclohexylamine With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

37
[ 25016-11-9 ]
[ 167408-67-5 ]
[ 109-85-3 ]
C₁₅H₁₉N₃O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-methylpyrazole-4-carbaldehyde; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester; 2-methoxyethylamine With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

38
[ 25016-11-9 ]
[ 167408-67-5 ]
[ 5332-73-0 ]
C₁₆H₂₁N₃O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-methylpyrazole-4-carbaldehyde; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester; 3-methoxypropylamine With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

39
[ 25016-11-9 ]
[ 167408-67-5 ]
[ 106-49-0 ]
C₁₈H₁₈N₄O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-methylpyrazole-4-carbaldehyde; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester; <i>p</i>-toluidine With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

40
[ 25016-11-9 ]
[ 167408-67-5 ]
[ 109-55-7 ]
C₁₇H₂₄N₄O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-methylpyrazole-4-carbaldehyde; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester; 1-amino-3-(dimethylamino)propane With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

41
[ 25016-11-9 ]
[ 167408-67-5 ]
[ 100-36-7 ]
C₁₈H₂₆N₄O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-methylpyrazole-4-carbaldehyde; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester; N,N-diethylethylenediamine With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

42
[ 2038-03-1 ]
[ 25016-11-9 ]
[ 167408-67-5 ]
C₁₈H₂₄N₄O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-(2-AMINOETHYL)MORPHOLINE; 1-methylpyrazole-4-carbaldehyde; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

43
[ 3731-52-0 ]
[ 25016-11-9 ]
[ 167408-67-5 ]
C₁₈H₁₈N₄O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-Aminomethylpyridine; 1-methylpyrazole-4-carbaldehyde; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

44
[ 25016-11-9 ]
[ 5036-48-6 ]
[ 167408-67-5 ]
C₁₈H₂₁N₅O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-methylpyrazole-4-carbaldehyde; 3-(1H-imidazol-1-yl)propan-1-amine; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

45
[ 3829-80-9 ]
[ 25016-11-9 ]
[ 167408-67-5 ]
C₁₈H₁₈N₄O₅S [ No CAS ]

Reference： [1]ACS Combinatorial Science,2012,vol. 14,p. 631 - 635

46
[ 25016-11-9 ]
[ 28466-21-9 ]
[ 167408-67-5 ]
C₁₈H₂₁N₅O₃ [ No CAS ]

Reference： [1]ACS Combinatorial Science,2012,vol. 14,p. 631 - 635

47
[ 25016-11-9 ]
[ 2289-75-0 ]
[ 167408-67-5 ]
C₁₇H₁₈N₄O₃S [ No CAS ]

Reference： [1]ACS Combinatorial Science,2012,vol. 14,p. 631 - 635

48
[ 25016-11-9 ]
[ 17647-70-0 ]
[ 167408-67-5 ]
C₁₅H₁₅N₅O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-methylpyrazole-4-carbaldehyde; 3-amino-4-methylfurazan; 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester With acetic acid Reflux; Stage #2: With water at 20℃; for 2h; Sonication;

Reference： [1]Ryabukhin, Sergey V.; Panov, Dmitriy M.; Plaskon, Andrey S.; Grygorenko, Oleksandr O. [ACS Combinatorial Science, 2012, vol. 14, # 12, p. 631 - 635]

49
[ 25016-11-9 ]
[ 93-85-6 ]
[ 167408-67-5 ]
C₂₀H₁₆N₄O₅S [ No CAS ]

Reference： [1]ACS Combinatorial Science,2012,vol. 14,p. 631 - 635

50
[ 167408-67-5 ]
[ 106-49-0 ]
[ 27258-33-9 ]
C₁₉H₁₉N₃O₃ [ No CAS ]

Reference： [1]ACS Combinatorial Science,2012,vol. 14,p. 631 - 635

51
[ 167408-67-5 ]
methyl 5-cyclopropylisoxazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
20%	With hydroxylamine hydrochloride In ethanol at 70℃; for 1h;	28 General procedure for preparation of methyl 5-cyclopropylisoxazole-3-carboxylate A mixture of methyl 4-cyclopropyl-2,4-dioxo-butanoate (900 mg, 5.3 mmol, 1.0 eq), hydroxylamine (1.1 g, 16 mmol, 3.0 eq, HC1 salt) in 10 mL of EtOH was stirred at 70 °C for 1 hour. The reactionmixture was concentrated under reduced pressure to give an oil. The oil was diluted with 10 mL of water and extracted twice with 16 mL of EtOAc. The combined organic layers were washed with 10 mL of brine, dried over Na2SO4, filtered and evaporated under reduced pressure to give a colorless oil which was purified by column chromatography (Si02, eluting with a gradient of petroleum ether:ethyl acetate = 100:1 to 20:1) to give 175mg of methyl 5-cyclopropylisoxazole-3-carboxylate (1.05 mmol, 20% yield) as a colorless oil.

Reference： [1]Current Patent Assignee: AQUINNAH PHARMACEUTICALS - WO2018/119395, 2018, A1 Location in patent: Page/Page column 145

52
[ 167408-67-5 ]
[ 108-94-1 ]
methyl 2-cyclopropyl-5,6,7,8-tetrahydroquinoline-4-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	Stage #1: cyclohexanone With ammonium acetate In 1,4-dioxane at 20℃; for 0.75h; Inert atmosphere; Green chemistry; Stage #2: 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester With chitosan In 1,4-dioxane at 80℃; for 18h; Inert atmosphere; Green chemistry; regioselective reaction;

Reference： [1]Jaiswal, Pradeep K.; Sharma, Vashundhra; Mathur, Manas; Chaudhary, Sandeep [Organic Letters, 2018, vol. 20, # 19, p. 6059 - 6063]

53
[ 167408-67-5 ]
3-(2-(allyloxy)-4-bromo-6-fluorophenyl)-1H-pyrazol-5-amine [ No CAS ]
methyl 2-(2-(allyloxy)-4-bromo-6-fluorophenyl)-7-cyclopropyl-pyrazolo[1,5-a]pyrimidine-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	In ethanol at 80℃; for 3h;	B Intermediate J9 : methyl 2-(2-(allyloxy)-4-bromo-6-fluorophenyl)-7-cyclopropyl- pyrazo lo [ 1 ,5 -a]pyrimidine-5 -carboxylate A mixture of J8 (14.4 g; 46.1 mmol) and Methyl 4-cyclopropyl-2,4-dioxobutanoate [167408-67-5] (8.26 g; 46.1 mmol) in EtOH (200 mL) was stirred at 80 °C for 3 h. The mixture was cooled to rt and a precipitate was formed. The precipitate was filtered and dried on the frit to give intermediate J9 as yellow solid (7.96 g, 38%).

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2019/106004, 2019, A1 Location in patent: Page/Page column 219; 221

54
[ 167408-67-5 ]
[ 934-22-5 ]
[ 15164-44-0 ]
C₂₁H₁₆IN₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	Stage #1: 5-aminobenzimidazole; p-(iodophenyl)carboxaldehyde With acetic acid In ethanol at 80℃; for 0.333333h; Stage #2: 4-cyclopropyl-2,4-dioxo-butyric acid methyl ester In ethanol Heating;	A solution of 4-iodobenzaldehyde (1.36 mg, 5.88 mmol) and 1H-benzo[d]imidazol-6- amine (782 mg, 1.0 eq.) in ethanol (10 mL) and acetic acid (0.5 mL) was heated at 80oC for 20 mins. Methyl 4-cyclopropyl-2,4-dioxobutanoate 1 (1.0 g, 1.0 eq.) was added dropwise and the reaction was heated overnight. The reaction was cooled to 0oC and compound 2 was collected by filtration and isolated as a brown solid (1.57 g, 55%).

Reference： [1]Current Patent Assignee: SCENIC HOLDING BV - WO2021/9068, 2021, A1 Location in patent: Page/Page column 403-404

55
[ 167408-67-5 ]
4-Hydrazino-N-methylbenzenemethanesulphonamide hydrochloride [ No CAS ]
5-cyclopropyl-1-(4-((N-methylsulfamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: methyl 4-cyclopropyl-2,4-dioxobutanoate; 4-Hydrazino-N-methylbenzenemethanesulphonamide hydrochloride In ethanol at 85℃; for 12h; Stage #2: With lithium hydroxide monohydrate; lithium hydroxide monohydrate In tetrahydrofuran; methanol at 20℃; for 2h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 1. To a solution of acetone (6a, 580 mg, 10 mmol) and dimethyloxalate (7, 1.18 g, 10 mmol) in anhydrous methanol (50 mL) was degassed with argon and cooled to 0 °C in an ice bath. 30% sodium methanolate in methanol (20 mmol) was added dropwise into the coldsolution and the mixture was allowed to warm to room temperature. After 12 h, the resultant mixture was quenched with conc. HCl (5 mL)and concentrated in vacuo. The residue was then diluted with water (50 mL) and extracted with EA (50 mL). The organic phase was separated, dried over anhydrous sodium sulfate, filtered and concentrated to give methyl acetopyruvate (8a) which was directly used in the next step without further purification. Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol)in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid. Step 3. To a solution of 10a and 11a (100mg) in 2:2:1 MeOH/THF/H2O (5mL) was added 1M LiOH (1mL) and stirred at room temperature. After 2h, the mixture was concentrated, diluted with water (5mL), acidified with 2M HCl (1mL) and filtered. The filtrate cake was washed with water and dried under vacuum to give the 12a (73mg) as a white solid.
	Stage #1: methyl 4-cyclopropyl-2,4-dioxobutanoate; 4-Hydrazino-N-methylbenzenemethanesulphonamide hydrochloride In ethanol at 85℃; for 12h; Stage #2: With lithium hydroxide monohydrate; lithium hydroxide monohydrate In tetrahydrofuran; methanol at 20℃; for 2h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 1. To a solution of acetone (6a, 580 mg, 10 mmol) and dimethyloxalate (7, 1.18 g, 10 mmol) in anhydrous methanol (50 mL) was degassed with argon and cooled to 0 °C in an ice bath. 30% sodium methanolate in methanol (20 mmol) was added dropwise into the coldsolution and the mixture was allowed to warm to room temperature. After 12 h, the resultant mixture was quenched with conc. HCl (5 mL)and concentrated in vacuo. The residue was then diluted with water (50 mL) and extracted with EA (50 mL). The organic phase was separated, dried over anhydrous sodium sulfate, filtered and concentrated to give methyl acetopyruvate (8a) which was directly used in the next step without further purification. Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol)in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid. Step 3. To a solution of 10a and 11a (100mg) in 2:2:1 MeOH/THF/H2O (5mL) was added 1M LiOH (1mL) and stirred at room temperature. After 2h, the mixture was concentrated, diluted with water (5mL), acidified with 2M HCl (1mL) and filtered. The filtrate cake was washed with water and dried under vacuum to give the 12a (73mg) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

56
[ 64-17-5 ]
[ 167408-67-5 ]
4-Hydrazino-N-methylbenzenemethanesulphonamide hydrochloride [ No CAS ]
methyl 5-cyclopropyl-1-(4-((N-methylsulfamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate [ No CAS ]
ethyl 5-cyclopropyl-1-(4-((N-methylsulfamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol)in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as awhite solid.
	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol)in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as awhite solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	167408-67-5	MDL No. :	MFCD04967381
Formula :	C₈H₁₀O₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	MFRDTCKJOFHQDZ-UHFFFAOYSA-N
M.W :	170.16	Pubchem ID :	16227056
Synonyms :

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H317-H319	Packing Group:	N/A
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
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

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

[ CAS No. 167408-67-5 ] {[proInfo.proName]}

Quality Control of [ 167408-67-5 ]

Related Doc. of [ 167408-67-5 ]

Product Details of [ 167408-67-5 ]

Safety of [ 167408-67-5 ]

Application In Synthesis of [ 167408-67-5 ]

[ 167408-67-5 ] Synthesis Path-Downstream 1~56

Related Functional Groups of
[ 167408-67-5 ]

Aliphatic Cyclic Hydrocarbons

Esters

Ketones

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

[ CAS No. 167408-67-5 ] {[proInfo.proName]}

Quality Control of [ 167408-67-5 ]

Related Doc. of [ 167408-67-5 ]

Product Details of [ 167408-67-5 ]

Safety of [ 167408-67-5 ]

Application In Synthesis of [ 167408-67-5 ]

[ 167408-67-5 ] Synthesis Path-Downstream 1~56

Related Functional Groups of [ 167408-67-5 ]

Aliphatic Cyclic Hydrocarbons

Esters

Ketones

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 167408-67-5 ]