37687-18-6|1-(1-Methyl-1h-pyrazol-4-yl)-ethanone| Ambeed

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Quality Control of [ 37687-18-6 ] Purity: 97% SDS Specification

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Product Details of [ 37687-18-6 ]

CAS No. :	37687-18-6
Formula :	C₆H₈N₂O
M.W :	124.14
SMILES Code :	CN1C=C(C=N1)C(C)=O
MDL No. :	MFCD00159640
InChI Key :	PINVCRAZGLSROU-UHFFFAOYSA-N
Pubchem ID :	3596939

Safety of [ 37687-18-6 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 37687-18-6 ] Show Less

Physicochemical Properties

Num. heavy atoms	9
Num. arom. heavy atoms	5
Fraction Csp3	0.33
Num. rotatable bonds	1
Num. H-bond acceptors	2.0
Num. H-bond donors	0.0
Molar Refractivity	33.68
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	34.89 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.28
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	-0.08
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	0.62
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	-0.25
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	0.61
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	0.44

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-0.9
Solubility	15.5 mg/ml ; 0.125 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-0.2
Solubility	78.2 mg/ml ; 0.63 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-1.09
Solubility	10.1 mg/ml ; 0.0815 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-7.11 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	1.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	1.26

Application In Synthesis of [ 37687-18-6 ]

* 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.

Downstream synthetic route of [ 37687-18-6 ]

[ 37687-18-6 ] Synthesis Path-Downstream 1~35

2
[ 40534-33-6 ]
[ 37687-18-6 ]

Yield	Reaction Conditions	Operation in experiment
91%	With manganese(IV) oxide; In dichloromethane; at 0 - 20℃; for 14h;	3) 1-(1-Methyl-1H-pyrazol-4-yl) ethanone In an argon atmosphere and at 0C, manganese(IV) oxide (activated, <5 micron, 209 g) was added to a solution of the above 1-(1-methyl-1H-pyrazol-4-yl)ethanol (20.2 g) in dichloromethane (202 mL), and the mixture was stirred for 14 hours at room temperature. Solid matter in the reaction mixture was removed through filtration, and the solvent of the filtrate was evaporated under reduced pressure, to thereby give 1-(1-methyl-1H-pyrazol-4-yl)ethanone as a solid product (18.1 g, 91%). 1H-NMR(400MHz,CDCl3)delta:2.42(3H,s), 3.94(3H,s), 7.86(1H,s), 7.89(1H,s). ESI-MSm/z:125(M+H)+.

References: [1]Patent: EP1762568,2007,A1 .Location in patent: Page/Page column 62.

3
[ 95-92-1 ]
[ 37687-18-6 ]
[ 873221-73-9 ]

Yield	Reaction Conditions	Operation in experiment
79%		4) 4-(1-Methyl-1H-pyrazol-4-yl)-2,4-dioxobutanoic acid ethyl ester In an argon atmosphere and at room temperature, diethyl oxalate (17.5 mL) was added to a solution of sodium ethoxide (8.77 g) in ethanol (80 mL), and the mixture was stirred for 10 minutes at room temperature. A solution of the above <strong>[37687-18-6]1-(1-methyl-1H-pyrazol-4-yl)ethanone</strong> (8.00 g) in ethanol (80 mL) was added to the reaction mixture, and the resultant mixture was stirred for 90 minutes at room temperature. The reaction mixture was partitioned between water and diethyl ether. Saturated aqueous ammonium chloride was added to the aqueous layer, and the mixture was extracted with chloroform. The organic layer was dried over sodium sulfate anhydrate. After a filtration step, the solvent was removed under reduced pressure, to thereby give 4-(1-methyl-1H-pyrazol-4-yl)-2,4-dioxobutanoic acid ethyl ester as a solid product (11.4 g, 79%). 1H-NMR(400MHz,CDCl3)delta:1.39-1.42(3H,m), 3.98(3H,s), 4.36-4.41(2H,m), 6.69(1H,s), 7.98(2H,m). EI-MSm/z:224 (M+).

References: [1]Patent: EP1762568,2007,A1 .Location in patent: Page/Page column 62-63.

4
[ 37687-18-6 ]
[ 706819-66-1 ]

Yield	Reaction Conditions	Operation in experiment
89%	With pyridinium perbromide hydrobromide; In ethanol; dichloromethane; at 20℃; for 3h;	B. Synthesis of 2-bromo-<strong>[37687-18-6]1-(1-methyl-1H-pyrazol-4-yl)ethanone</strong> A solution of <strong>[37687-18-6]1-(1-methyl-1H-pyrazol-4-yl)ethanone</strong> (28.5 g, 230 mmol) in dichloromethane (400 mL) was diluted with absolute ethanol (100 mL) and treated portion-wise with pyridinium tribromide (95%, 77.3 g, 230 mmol). The reaction was stirred at room temperature for 3 hours, during which time it solidified; the mixture was diluted with dichloromethane (300 mL) and water (400 mL), treated with sodium sulfite (5 g) and stirred for 10 minutes. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was washed with water (200 mL), collected by filtration, washed again with water, and dried to afford the product as an off-white solid. Yield: 41.6 g, 205 mmol, 89%. 1H NMR (500 MHz, CDCl3) delta 7.97-7.98 (m, 1H), 7.95 (br s, 1H), 4.17 (s, 2H), 3.95-3.96 (m, 3H).
85%	With pyridine hydrobromide perbromide; In ethanol; dichloromethane; at 15℃; for 18h;Inert atmosphere; Large scale;	Two identical reactions were carried out in parallel.10159] To a solution of i-(i-methyl-iH-pyrazol-4-yl) ethan-i-one (Preparation 5, 620 g, 5 mol) in DCM (12 L) and ethanol (3 L) was added PyHl3r3 (1.6 kg, 5 mol) at about 15 C. The mixture was stirred at about 15 C. for about 18 hrs. The two reaction mixtures were combined, quenched with water (10 L), separated, and the aqueous phase was extracted with DCM (4xiO L). The combined DCM extracts were dried (Na2SO4) and concentrated to remove about 69 L of solvent. The residue was diluted with petroleum ether (5 L), stirred at about 15 C. for about 30 mm and the mixture was filtered. The precipitate was dried to afford the title compound as a yellow solid (1.73 kg, 85%).?H NMR (400 MHz, CDCl3) delta: 7.97 (s, iH), 7.91 (s, 1H), 4.17 (s, 2H), 3.93 (s, 3H). LCMS mlz=203.i [MH] (798r isotope)
20%	With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; for 24h;Reflux; UV-irradiation;	1-(1-Methyl-1H-pyrazol-4-yl)ethanone (18 g, 145 mmol) and NBS (31 g, 174 mmol) were added to the reaction flask.Add CCl4 (80 mL) to dissolve, and add AIBN (2.4 g, 14.5 mmol) in portions under reflux, and react under 365 nm UV irradiation for 24 h.After the reaction is completed, the system is poured into ice water, extracted with dichloromethane, dried over anhydrous sodium sulfate, and the solvent is removed for column chromatography.(eluent: Petroleum ether/EtOAc (v/v) = 5/1),5.9 g of a yellow oily product were obtained in a yield: 20%.

	With hydrogen bromide; bromine; In chloroform; acetic acid; at 20℃; for 1h;	2-Bromo- 1 -( 1 -methyl- 1 H-pyrazol-4-yl)ethanoneTo a solution of 1 -(I -methyl- lH-pyrazol-4-yl)ethanone (0.602 g, 4.85 mmol) in chloroform (20 mL) and of 33% HBr in acetic acid (3.92 mg, 0.05 mmol) was added dropwise a chloroform solution containing Br2 (0.262 mL, 5.09 mmol) via an addition funnel. The reaction mixture was stirred at room temperature for 1 h and then concentrated under reduced pressure. The crude solid was triturated in ethyl acetate, filtered, washed and dried in vacuo. The free base was obtained by triturating the product in 5% NaHCtheta3 for 2 h. The solid that formed were collected by filtration, washed with water and isopropyl alcohol and then dried in vacuo. Isolation gave 874 mg of the title compound. LC/MS (ES+)(M+H)+: 204 for C6H7BrN2O.1H NMR (300 MHz, d6-DMSO): 3.88 (s, 3H), 4.56 (s, 2H), 7.99 (s, IH), 8.47 (s, IH).
	With bromine; acetic acid;hydrogen bromide; In chloroform; at 20℃; for 1h;	Intermediate 282-Bromo- 1 -( 1 -methyl- 1 H-pyrazol-4-vDethanoneIn a 25 mL flask, 1 -(I -methyl- lH-pyrazol-4-yl)ethanone (0.602 g, 4.85 mmol) was dissolved in chloroform (20 mL). The colorless solution was made acidic with the addition of a few drops of HBr in acetic acid (3.92 mg, 0.05 mmol). A chloroform solution containing Br2 (0.262 mL, 5.09 mmol) was added dropwise via an addition funnel. The reaction mixture was stirred at room temperature for 1 h, and then concentrated under reduced pressure. The crude solid was triturated in ethyl acetate, filtered, and dried in vacuo. The free base was obtained by triturating the product in 5% NaHCCb for 2 h. The solid was collected by filtration, washed with water, isopropyl alcohol and then dried in vacuo. Isolation gave 874 mg of the title compound.LC/MS (ES+)[(M+H)+]: 204 for C6H7BrN2O.1H NMR (300 MHz, d6-DMSO): 3.88 (s, 3H), 4.56 (s, 2H), 7.99 (s, IH), 8.47 (s, IH).
2 g	With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; at 80℃; for 14h;	Method 31 Synthesis of 2-bromo-1-(6-methyl-3-pyridyl)ethanone (Intermediate 45) To a solution of R-12 (10 g, 79.3 mmol) in MeCN (200 mL) at 0 C. is added N,O-dimethylhydroxylaminehydrochloride (8.5 g, 87.2 mmol), EDCI (18.2 g, 95.2 mmol), 1-hydroxybenzotriazole (3.2 g, 23.8 mmol) followed by triethylamine (20.5 mL, 158 mmol) and stirred at room temperature 15 h. The reaction mixture is partitioned between water and EtOAc. The collected organics are dried with anhydrous Na2SO4, filtered, and concentrated in vacuo to give I-43 (12 g) m/z 170.0 [M+H].

References: [1]Patent: US2012/214791,2012,A1 .Location in patent: Page/Page column 21.
[2]Journal of Medicinal Chemistry,2018,vol. 61,p. 1001 - 1018.
[3]Patent: US2017/240552,2017,A1 .Location in patent: Paragraph 0157; 0158; 0159; 0160; 0161.
[4]Patent: CN110294747,2019,A .Location in patent: Paragraph 0147-0148; 0152-0154.
[5]Patent: WO2010/136817,2010,A1 .Location in patent: Page/Page column 157-158.
[6]Patent: WO2011/24004,2011,A1 .Location in patent: Page/Page column 244.
[7]Patent: US2013/196967,2013,A1 .Location in patent: Paragraph 0251; 0254.

5
[ 37687-18-6 ]
[ 1186111-09-0 ]

References: [1]Patent: WO2011/24004,2011,A1 .

6
[ 37687-18-6 ]
[ 85290-80-8 ]
[ 1006327-32-7 ]

References: [1]Chemistry of Heterocyclic Compounds,2011,vol. 47,p. 695 - 699.

7
[ 37687-18-6 ]
2-methyl-2H-pyrazole-3-carboxylic acid ethyl ester [ No CAS ]
[ 1346006-21-0 ]

References: [1]Chemistry of Heterocyclic Compounds,2011,vol. 47,p. 695 - 699.

8
[ 15803-02-8 ]
[ 78191-00-1 ]
[ 37687-18-6 ]

Yield	Reaction Conditions	Operation in experiment
57%		A. Synthesis of 1-(1-methyl-1H-pyrazol-4-yl)ethanone 4-Bromo-1-methyl-1H-pyrazole (41.3 mL, 400 mmol), was dissolved in tetrahydrofuran (750 mL) and cooled to -78 C. N-Butyllithium (2.5 M solution in hexanes, 160 mL, 400 mmol) was added drop-wise over 30 minutes, and the resulting mixture was stirred for 1 hour at -78 C. After drop-wise addition of a solution of N-methoxy-N-methylacetamide (40.9 mL, 400 mmol) in tetrahydrofuran (100 mL) to the -78 C. reaction mixture, the cooling bath was allowed to warm to 0 C. over 4 hours. The reaction was then quenched with saturated aqueous sodium chloride solution (50 mL), and volatiles were removed in vacuo. The residue was diluted with ethyl acetate (1000 mL), treated with magnesium sulfate, and stirred for 30 minutes before being filtered and concentrated in vacuo. Purification was carried out via silica gel chromatography (material was loaded in a minimum amount of dichloromethane; Gradient: 5% to 100% ethyl acetate in heptane) to provide a pale yellow oil that solidified on standing. Yield: 28.5 g, 230 mmol, 57%. 1H NMR (500 MHz, CDCl3) delta 2.37 (s, 3H), 3.90 (s, 3H), 7.83 (s, 1H), 7.84 (s, 1H).

References: [1]Angewandte Chemie - International Edition,2019,vol. 58,p. 1062 - 1066.
Angew. Chem.,2019,vol. 131,p. 1074 - 1078,5.
[2]Patent: US2012/214791,2012,A1 .Location in patent: Page/Page column 21.
[3]Journal of Medicinal Chemistry,2018,vol. 61,p. 1001 - 1018.

9
[ 37687-18-6 ]
[ 1394033-56-7 ]

References: [1]Patent: US2012/214791,2012,A1 .
[2]Patent: US2012/214791,2012,A1 .

10
[ 37687-18-6 ]
[ 1394033-54-5 ]

References: [1]Patent: US2012/214791,2012,A1 .
[2]Patent: US2012/214791,2012,A1 .
[3]Journal of Medicinal Chemistry,2018,vol. 61,p. 1001 - 1018.

11
[ 37687-18-6 ]
[ 1394034-53-7 ]

References: [1]Patent: US2012/214791,2012,A1 .
[2]Journal of Medicinal Chemistry,2018,vol. 61,p. 1001 - 1018.

12
[ 37687-18-6 ]
[ 1394034-56-0 ]

References: [1]Patent: US2012/214791,2012,A1 .
[2]Journal of Medicinal Chemistry,2018,vol. 61,p. 1001 - 1018.

13
[ 37687-18-6 ]
[ 1394034-57-1 ]

References: [1]Patent: US2012/214791,2012,A1 .
[2]Journal of Medicinal Chemistry,2018,vol. 61,p. 1001 - 1018.

14
[ 37687-18-6 ]
[ 1394034-58-2 ]

References: [1]Patent: US2012/214791,2012,A1 .
[2]Patent: US2012/214791,2012,A1 .
[3]Journal of Medicinal Chemistry,2018,vol. 61,p. 1001 - 1018.

15
[ 37687-18-6 ]
[ 1394034-67-3 ]

References: [1]Patent: US2012/214791,2012,A1 .

16
[ 37687-18-6 ]
2-methyl-4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-amine trifluoroacetate [ No CAS ]

References: [1]Patent: US2012/214791,2012,A1 .

17
[ 37687-18-6 ]
4-(azetidin-1-yl)-7-methyl-5-(1-methyl-1H-pyrazol-4-yl)imidazo[5,1-f][1,2,4]triazine [ No CAS ]

References: [1]Patent: US2012/214791,2012,A1 .

18
[ 5952-92-1 ]
[ 37687-18-6 ]

References: [1]Journal of Heterocyclic Chemistry,2012,vol. 49,p. 1422 - 1424.
[2]Patent: US2013/196967,2013,A1 .

19
[ 79583-19-0 ]
[ 37687-18-6 ]

References: [1]Journal of Heterocyclic Chemistry,2012,vol. 49,p. 1422 - 1424.

20
diethyl (1-methylpyrazol-4-yl)carbonyl malonate [ No CAS ]
[ 37687-18-6 ]

References: [1]Journal of Heterocyclic Chemistry,2012,vol. 49,p. 1422 - 1424.

21
[ 1283120-11-5 ]
[ 75-16-1 ]
[ 37687-18-6 ]

Yield	Reaction Conditions	Operation in experiment
8 mg	In tetrahydrofuran; at -78 - 20℃; for 14h;	Method 31 Synthesis of 2-bromo-1-(6-methyl-3-pyridyl)ethanone (Intermediate 45) To a solution of R-12 (10 g, 79.3 mmol) in MeCN (200 mL) at 0 C. is added N,O-dimethylhydroxylaminehydrochloride (8.5 g, 87.2 mmol), EDCI (18.2 g, 95.2 mmol), 1-hydroxybenzotriazole (3.2 g, 23.8 mmol) followed by triethylamine (20.5 mL, 158 mmol) and stirred at room temperature 15 h. The reaction mixture is partitioned between water and EtOAc. The collected organics are dried with anhydrous Na2SO4, filtered, and concentrated in vacuo to give I-43 (12 g) m/z 170.0 [M+H].

References: [1]Patent: US2013/196967,2013,A1 .Location in patent: Paragraph 0251; 0253.

22
[ 930-36-9 ]
[ 108-24-7 ]
[ 37687-18-6 ]

Yield	Reaction Conditions	Operation in experiment
72%	With sulfuric acid; at 150℃; for 3h;Inert atmosphere; Large scale;	Two identical reactions were carried out in parallel.To a mixture of 1 -methylpyrazole (750 g, 9.16 mol) and acetic anhydride (1.7 kg, 16.67 mol) was added concentrated H2S04 (75 g, 0.75 mol) at about 20 C. The reaction mixture was heated at about 150 C. for about 3 hrs. After cooling, the two mixtures were combined, poured into ice-water (15 L), adjusted to about pH 10 with 20% aq. NaOH and extracted with DCM (4x10 L). The combined DCM extracts were dried (Na2SO4) and concentrated to afford the title compound as a brown oil (1240 g, 72%).?H NMR (400 MHz, CDCl3) delta: 7.86 (s, 1H), 7.84 (s, 1H), 3.92 (s, 3H), 2.40 (s, 3H).GCMS mlz=109.0 [M-CH3]+
71%	With sulfuric acid; at 140℃; for 12h;Inert atmosphere;	N-methylpyrazole (16.4 g, 200 mmol) and acetic anhydride (38 mL, 400 mmol) were added to the reaction flask.Concentrated sulfuric acid (1 mL, 20 mmol) was added dropwise with stirring, and then reacted under a nitrogen atmosphere at 140 C for 12 h.After the reaction is completed, the system is poured into ice water, extracted with dichloromethane, dried over anhydrous sodium sulfate, and the solvent is removed for column chromatography.(Eluent: Petroleum ether / EtOAc (v/v) = 3/1) afforded 17.7 g of product as a yellow oil. Yield: 71%.
69%	With sulfuric acid; for 5h;Inert atmosphere; Reflux;	General procedure: To a stirred mixture of pyrazole (200 mmol) and the appropriate acid anhydride (350 mmol, 1.75 equiv), concd H2SO4(0.2 mL) was added, and the resulting mixture was stirred under a nitrogen atmosphere in an oil bath until the pyrazole was consumed. For low boiling components, this mixture was heated at reflux. Reaction conditions (temperature and time) are given in Table 2. When the reaction was complete, volatile compounds were removed under reduced pressure and the residue was poured onto 100 mL crushed ice. The reaction mixture was neutralized under vigorous stirring by the addition of 20% aqueous NaOH or (in the case of fluorinated ketones) solid KHCO3 to adjust pH to 7-8. The ketone was extracted with CH2Cl2(3 × 50 mL) and the combined organic phases were washed with brine (50 mL), dried over MgSO4, and evaporated under reduced pressure. The resulting crude ketone was purified by either distillation or recrystallization from the appropriate solvent.

References: [1]Patent: US2017/240552,2017,A1 .Location in patent: Paragraph 0152; 0153; 0154; 0155; 0156.
[2]Patent: CN110294747,2019,A .Location in patent: Paragraph 0147-0151.
[3]Synthesis,2013,vol. 45,p. 2188 - 2192.

23
[ 105-56-6 ]
[ 37687-18-6 ]
[ 1456890-46-2 ]

References: [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 7278 - 7288.

24
[ 39806-90-1 ]
[ 111-34-2 ]
[ 37687-18-6 ]