Home Cart 0 Sign in  

[ CAS No. 25016-11-9 ]

{[proInfo.proName]} ,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 25016-11-9
Chemical Structure| 25016-11-9
Structure of 25016-11-9 * Storage: {[proInfo.prStorage]}

Quality Control of [ 25016-11-9 ]

Related Doc. of [ 25016-11-9 ]

SDS
Alternatived Products of [ 25016-11-9 ]
Alternatived Products of [ 25016-11-9 ]

Product Details of [ 25016-11-9 ]

CAS No. :25016-11-9 MDL No. :MFCD00460465
Formula : C5H6N2O Boiling Point : -
Linear Structure Formula :- InChI Key :-
M.W :110.11 g/mol Pubchem ID :573117
Synonyms :

Safety of [ 25016-11-9 ]

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

Application In Synthesis of [ 25016-11-9 ]

  • Upstream synthesis route of [ 25016-11-9 ]
  • Downstream synthetic route of [ 25016-11-9 ]

[ 25016-11-9 ] Synthesis Path-Upstream   1~10

  • 1
  • [ 930-36-9 ]
  • [ 68-12-2 ]
  • [ 25016-11-9 ]
YieldReaction ConditionsOperation in experiment
77.7%
Stage #1: at 100℃; for 2 h;
Stage #2: at 20℃;
Stage #3: With sodium hydroxide In water
POCl3 (54.3g, 0.35mol) was added dropwise to a stirred solution of 1 -methyl- lH-pyrazole (29.1g, 0.35mol) in dry DMF (9OmL) at 1000C and the stirring was continued for 2h. Then the reaction mixture was cooled and poured into ice water (35OmL), basified to pH 8 with 2 mol/L of NaOH, extracted with CHCl3, dried over anhydrous Na2 SO4 and concentrated in vacuum to give crude product. It was purified with chromatography to give compound 1 -methyl- lH-pyraozle-4-carboxaldehyde (30g, 77.7percent) as a yellow oil. ES-MS m/z: l l l(M+H+).
66%
Stage #1: at 0 - 80℃; for 1.66667 h;
Stage #2: at 85 - 115℃; for 5.5 h;
1)
1-Methyl-1H-pyrazole-4-carboaldehyde
In an argon atmosphere, phosphorus oxychloride (65.3 mL) was added dropwise to N,N-dimethylformamide (54.2 mL) at 0°C over 30 minutes, and the mixture was stirred at room temperature for 1 hour and 80°C for 10 minutes.
Subsequently, 1-methylpyrazole (25.0 g) was added dropwise to the reaction mixture over 30 minutes.
The reaction mixture was stirred at 85°C for 1 hour, at 100°C for 3 hours, and at 115°C for 1 hour, and then allowed to cool in air.
The reaction mixture was added ice-water (1 L), and the mixture was stirred for 20 hours.
The reaction mixture was partitioned between 1M aqueous sodium hydroxide (2 L) and chloroform, and the organic layer was dried over sodium sulfate anhydrate.
After a filtration step, the solvent was evaporated under reduced pressure, and the residue was purified through silica gel column chromatography (chloroform - methanol), to thereby give 1-methyl-1H-pyrazole-4-carboaldehyde as an oily product (22.1 g, 66percent).
1H-NMR(400MHz,CDCl3)δ:3.97(3H,s), 7.91(1H,s), 7.96(1H,s), 9.85(1H,s).
ESI-MSm/z:111(M+H)+.
66%
Stage #1: at 0 - 80℃; for 1.66667 h;
Stage #2: at 85 - 115℃; for 5.5 h;
Stage #3: at 0℃; for 20 h;
1) 1-Methyl-1H-pyrazole-4-carbaldehyde Under an argon atmosphere, phosphorus oxychloride (65.3 mL) was added dropwise to N, N-dimethylformamide (54.2 mL) at 0°C over 30 minutes, and then the resultant mixture was stirred for 1 hour at room temperature. The reaction solution was stirred for 10 minutes at 80°C, and then 1-methylpyrazole (25.0 g) was added dropwise thereto over 30 minutes. Furthermore, the reaction solution was stirred for 1 hour at 85°C, for 3 hours at 100°C, and for 1 hour at 115°C. After air cooling, the reaction solution was added to ice water (1 L), and stirred for 20 hours. An aqueous 1 M sodium hydroxide solution (2 L) and chloroform were added to the reaction solution, and the mixture was partitioned. The organic layer was dried over anhydrous sodium sulfate. After separation by filtration, a residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (chloroform-methanol), to obtain 1-methyl-1H-pyrazole-4-carbaldehyde (22.1 g, 66percent) as an oily product. 1H-NMR(400MHz, CDCl3)δ: 3.97(3H, s), 7.91(1H, s), 7.96(1H, s), 9.85(1H, s). ESI-MSm/z: 111(M+H)+.
59%
Stage #1: at 0 - 20℃;
Stage #2: at 80 - 95℃;
Phosphorus oxychloride (6.92 g, 45.1 mmol, 1.50 equiv.) was cooled to 0 0C and then added drop-wise to anhydrous DMF (3.50 mL, 45.2 mmol, 1.50 equiv.) at 0 0C. The mixture was stirred 1 hour at room temperature and was then heated to 80 0C. The compound of formula VIII (2.50 mL, 30.2 mmol) was then added drop-wise to the reaction, and the resulting mixture was stirred 3 hours at 95 0C. The reaction was then quenched by slow addition to ice (40 g). The pH of the resulting solution was 2, and it was raised to 5 by slow addition of 12N aqueous sodium hydroxide solution (11.2 mL). The resulting aqueous solution was extracted with dichloromethane and/or ether (7 x 40 mL), and additional sodium hydroxide was added during extraction, as needed, to maintain a pH of 5. The extracts were then combined, dried over sodium sulfate, filtered and concentrated to yield a brown oil (3.79 g, 59percent yield).
40%
Stage #1: at 100℃; for 2 h;
Stage #2: at 0℃;
Phosphorus oxychloride (181 g, 1.18 mol) was added dropwise to a stirred solution of 1- methylpyrazole (97 g, 1.18 mol) in dry DMF (240 ML) at 100 °C. The reaction mixture was maintained at this temperature for 2 h, cooled to room temperature, poured onto ice water (1 L), and basified to pH 8 by the addition of 2 M aqueous sodium hydroxide solution. The mixture was then extracted with chloroform (4X500 mL), the organic phase dried over anhydrous sodium sulfate, filtered, concentrated in vacuo to a brown oil and the excess DMF distilled away. The crude product was purified (SIO2, diethyl ether) to provide the title compound as a pale yellow oil (52 g, 40percent).
600 mg at 90℃; for 3 h; N-methylpyrazole (1.0 g, 1 eq.) was dissolved in N,N-dimethylformamide (2.8 ml, 3 eq.), phosphorus oxychloride (1.3ml, 1.2 eq.) was added dropwise at 90 °C over about 1 h. The mixture was reacted for another 2 h and then cooled. The reaction liquid was poured into iced water and adjusted with 10percent aqueous sodium hydroxide solution to PH 4∼5, extracted four times with dichloromethane, rinsed with water twice, and separated by column chromatography to give 600 mg product

Reference: [1] Patent: WO2008/144767, 2008, A1, . Location in patent: Page/Page column 117
[2] Patent: EP1762568, 2007, A1, . Location in patent: Page/Page column 62
[3] Patent: EP1785418, 2007, A1, . Location in patent: Page/Page column 78
[4] Patent: WO2008/153870, 2008, A1, . Location in patent: Page/Page column 29
[5] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 1, p. 471 - 474
[6] Tetrahedron Letters, 2016, vol. 57, # 24, p. 2601 - 2603
[7] Patent: WO2004/58763, 2004, A1, . Location in patent: Page 39
[8] Russian Chemical Bulletin, 2014, vol. 63, # 2, p. 443 - 456[9] Izv. Akad. Nauk, Ser. Khim., 2014, # 2, p. 443 - 456,14
[10] Pharmaceuticals, 2018, vol. 11, # 1,
[11] Journal of the Chemical Society, 1957, p. 3314
[12] Journal of Medicinal Chemistry, 2008, vol. 51, # 13, p. 3777 - 3787
[13] Patent: WO2012/76435, 2012, A1, . Location in patent: Page/Page column 28-29
[14] Patent: WO2013/39854, 2013, A1, . Location in patent: Page/Page column 29
[15] Patent: WO2014/2110, 2014, A1, . Location in patent: Page/Page column 140
[16] Patent: WO2014/2111, 2014, A1, . Location in patent: Page/Page column 33
[17] Patent: WO2014/62454, 2014, A1, . Location in patent: Page/Page column 33
[18] Patent: EP2725024, 2014, A1, . Location in patent: Paragraph 0140; 0141
[19] Patent: US2014/171431, 2014, A1, . Location in patent: Paragraph 0486; 0487
[20] Patent: US2015/112063, 2015, A1, . Location in patent: Paragraph 0191
[21] Patent: EP3239135, 2017, A1, . Location in patent: Paragraph 0130; 0131
  • 2
  • [ 35344-95-7 ]
  • [ 74-88-4 ]
  • [ 25016-11-9 ]
YieldReaction ConditionsOperation in experiment
87% With caesium carbonate In N,N-dimethyl-formamide at 60℃; To a solution of lH-pyrazole-4-carbaldehyde (1.00 g, 10.4 mmol) in DMF (40 mL) was added iodomethane (1.48 g, 10.4 mmol) and CS2CO3 (10 g, 31.2 mmol). After stirring at 60°C overnight, the reaction mixture was added water (20 mL) and extracted with EtOAc (50 mL x 3). The organic phase was washed with brine, dried over Na2S04 and concentrated to give intermediate 48 (1.00 g, 87percent yield).
Reference: [1] Patent: WO2018/50684, 2018, A1, . Location in patent: Page/Page column 67
  • 3
  • [ 930-36-9 ]
  • [ 25016-11-9 ]
Reference: [1] Patent: WO2014/2109, 2014, A1, . Location in patent: Page/Page column 131
  • 4
  • [ 18655-47-5 ]
  • [ 60-34-4 ]
  • [ 25016-11-9 ]
Reference: [1] Bulletin de la Societe Chimique de France, 1990, # 5, p. 660 - 666
  • 5
  • [ 15803-02-8 ]
  • [ 68-12-2 ]
  • [ 25016-11-9 ]
Reference: [1] Patent: EP1186604, 2002, A1, . Location in patent: Page 106
  • 6
  • [ 930-36-9 ]
  • [ 68-12-2 ]
  • [ 10025-87-3 ]
  • [ 25016-11-9 ]
Reference: [1] Journal of the Chemical Society, 1957, p. 3314
  • 7
  • [ 25016-11-9 ]
  • [ 5952-92-1 ]
YieldReaction ConditionsOperation in experiment
31%
Stage #1: With Jones reagent In acetone at 40℃;
Stage #2: With sodium hydroxide In water; acetone
To a solution of 1 -methyl- lH-pyraozle-4-carboxaldehyde (3Og, 0.27mol) in acetone (15OmL) was added dropwise Jones reagent (26OmL, prepared by dissolving 69.Og of O&3 in 59.8mL of conc.H24 and diluted to 26OmL with water.) at 400C. After reaction, the mixture was adjusted to pH 4 with 0.6mol/L of NaOH. Then the precipitate was collected by filtration. The filtrate was extracted with EA and dried over anhydrousNa24 and concentrated in vacuum to give 1 -methyl- lH-pyrazole-4-carboxylic acid (10.7g, 31percent). ES-MS m/z:127(M+H+).
Reference: [1] Patent: WO2008/144767, 2008, A1, . Location in patent: Page/Page column 118
[2] Journal of the Chemical Society, 1957, p. 3314
[3] Bulletin de la Societe Chimique de France, 1990, # 5, p. 660 - 666
  • 8
  • [ 25016-11-9 ]
  • [ 5952-92-1 ]
Reference: [1] Patent: US4792565, 1988, A,
  • 9
  • [ 25016-11-9 ]
  • [ 66121-71-9 ]
YieldReaction ConditionsOperation in experiment
95% With ammonium hydroxide; sodium bromate; acetic acid In water at 90 - 100℃; for 1 h; 1-Methyl-1H-pyrazole-4-carbaldehyde (11.0 g, 0.1 mol), sodium bromate (6.0 g, 0.04 mol) and 50 g of acetic acid (0.83 mol) were mixed at room temperature. Add 12.5 g of ammonia-containing molecular mass concentration of 25percent ammonia water and 100 ml of water. heating to 90 °C, the reaction is exothermic, maintaining the reaction temperature of 100 °C, refluxing reaction for 1 hour (to 1-methyl-1H-pyrazole-4-carbaldehyde reaction is complete), The reaction solution was cooled to room temperature, poured into ice water and quenched and diluted. neutralize until the reaction solution is neutral, extract with ethyl acetate, and dry. After concentrating the product, it is distilled under reduced pressure and recrystallized.The product obtained was 10.2 g, the yield was 95percent, and the purity was over 99percent.
Reference: [1] Patent: CN108707113, 2018, A, . Location in patent: Paragraph 0017
[2] Russian Journal of General Chemistry, 2012, vol. 82, # 10, p. 1720 - 1723[3] Zh. Obshch. Khim., 2012, vol. 82, # 10, p. 1716 - 1719,4
  • 10
  • [ 25016-11-9 ]
  • [ 112029-98-8 ]
YieldReaction ConditionsOperation in experiment
97%
Stage #1: With sodium tetrahydroborate In methanol at 20℃; for 3 h;
Stage #2: With hydrogenchloride; methanol In water at 0 - 20℃;
The compound of formula IX (3.48 g, 31.6 mmol) was dissolved in methanol (25 ml_) and sodium borohydride (2.50 g, 66.1 mmol, 2.09 equiv.) was added portion-wise with vigorous gas evolution. After stirring for 3 hours at room temperature, the reaction was cooled to 0 0C and slowly acidified to pH ~ 1 with 4N aqueous hydrochloric acid (20 ml_) over 55 minutes. A thick white slurry formed and this was stirred one hour at room temperature. The reaction was then basified by the gradual addition of saturated aqueous potassium carbonate solution (53.4 wtpercent K2CU3, 6.04 M; 10 ml_). This resulted in a clear, colorless solution (pH = 1.1), which was diluted with additional saturated potassium carbonate solution (200 ml_) and was extracted with ethyl acetate (2 x 200 ml_). The ethyl acetate extracts were combined, dried over sodium sulfate, filtered and concentrated to yield the compound of formula X as a light yellow oil (3.44 g, 97percent yield).
60.5% at 0 - 20℃; for 1 h; Step A
(1-methyl-1,1-pyrazol-4-yl)methanol
To a solution of 1-methyl-1H-pyrazole-4-carbaldehyde (0.500 g, 4.54 mmol) in methanol (10 mL, 200 mmol) at 0° C. was added sodium tetrahydroboride (0.515 g, 13.6 mmol).
The reaction was stirred at room temperature for 1 h, and then quenched with brine, and extracted with ethyl acetate (EtOAc) (3*).
The combined organic phases were washed with water, brine, dried over Na2SO4, and concentrated to give 0.308 g (60.5percent yield) of the final product as colorless oil, which was used directly for the next step without further purification. LC/MS found: 113.1 (M+1)+.
400 mg With lithium aluminium tetrahydride In tetrahydrofuran at 20℃; for 2 h; Cooling with ice Intermediate 69 (600mg, 1 eq.) was dissolved in tetrahydrofuran, and lithium aluminum hydride (210 mg, 1 eq.) was added under ice bath and the mixture was reacted at room temperature for 2 h. After completion of the reaction, 210 µl of water, 210 µl of 10percent aqueous sodium hydroxide solution, and 630 µl of water were successively added, followed by addition of anhydrous magnesium sulfate. The mixture was stirred for a while, filtered and evaporated to dryness to give 400 mg of an oil. MS (ESI): 113(M+H)
Reference: [1] Patent: WO2008/153870, 2008, A1, . Location in patent: Page/Page column 30
[2] Journal of Medicinal Chemistry, 2008, vol. 51, # 13, p. 3777 - 3787
[3] Russian Journal of General Chemistry, 2010, vol. 80, # 5, p. 1001 - 1003
[4] Patent: US2013/96144, 2013, A1, . Location in patent: Paragraph 0174
[5] Patent: EP3239135, 2017, A1, . Location in patent: Paragraph 0132; 0133
Historical Records

Related Functional Groups of
[ 25016-11-9 ]

Aldehydes

Chemical Structure| 304903-10-4

[ 304903-10-4 ]

1-Ethyl-1H-pyrazole-4-carbaldehyde

Similarity: 0.88

Chemical Structure| 25016-12-0

[ 25016-12-0 ]

1,3-Dimethyl-1H-pyrazole-4-carbaldehyde

Similarity: 0.86

Chemical Structure| 35344-95-7

[ 35344-95-7 ]

1H-Pyrazole-4-carbaldehyde

Similarity: 0.86

Chemical Structure| 1197230-88-8

[ 1197230-88-8 ]

1H-Pyrazole-4-carbaldehyde hydrochloride

Similarity: 0.84

Chemical Structure| 473249-36-4

[ 473249-36-4 ]

1-Propyl-1H-pyrazole-4-carbaldehyde

Similarity: 0.82

Related Parent Nucleus of
[ 25016-11-9 ]

Pyrazoles

Chemical Structure| 304903-10-4

[ 304903-10-4 ]

1-Ethyl-1H-pyrazole-4-carbaldehyde

Similarity: 0.88

Chemical Structure| 37687-18-6

[ 37687-18-6 ]

1-(1-Methyl-1h-pyrazol-4-yl)-ethanone

Similarity: 0.88

Chemical Structure| 25016-12-0

[ 25016-12-0 ]

1,3-Dimethyl-1H-pyrazole-4-carbaldehyde

Similarity: 0.86

Chemical Structure| 35344-95-7

[ 35344-95-7 ]

1H-Pyrazole-4-carbaldehyde

Similarity: 0.86

Chemical Structure| 1197230-88-8

[ 1197230-88-8 ]

1H-Pyrazole-4-carbaldehyde hydrochloride

Similarity: 0.84