[ CAS No. 3783-38-8 ]

Name: 3783-38-8|4-(Methoxycarbonyl)pyridine 1-oxide|95%
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Product Details of [ 3783-38-8 ]

CAS No. :	3783-38-8	MDL No. :	MFCD00128856
Formula :	C₇H₇NO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	XSGNXRNOZMUURC-UHFFFAOYSA-N
M.W :	153.14	Pubchem ID :	236636
Synonyms :

Safety of [ 3783-38-8 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P301+P312-P302+P352-P304+P340-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 3783-38-8 ]

* 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 [ 3783-38-8 ]
Downstream synthetic route of [ 3783-38-8 ]

[ 3783-38-8 ] Synthesis Path-Upstream 1~12

1
[ 3783-38-8 ]
[ 2459-09-8 ]

Reference： [1] Synthesis, 1989, # 8, p. 645 - 646
[2] Gazzetta Chimica Italiana, 1994, vol. 124, # 9, p. 385 - 386
[3] Journal of Heterocyclic Chemistry, 2018, vol. 55, # 2, p. 486 - 491
[4] Chemische Berichte, 1990, vol. 123, p. 647 - 649
[5] Synthetic Communications, 2002, vol. 32, # 11, p. 1681 - 1683
[6] Synlett, 2002, # 2, p. 349 - 351
[7] Synthetic Communications, 2003, vol. 33, # 23, p. 4137 - 4141
[8] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 18, p. 5583 - 5591

2
[ 3783-38-8 ]
[ 16420-13-6 ]
[ 2459-09-8 ]

Reference： [1] Journal of Heterocyclic Chemistry, 2007, vol. 44, # 2, p. 487 - 489

3
[ 3783-38-8 ]
[ 6937-03-7 ]

Reference： [1] Journal of Organic Chemistry, 2007, vol. 72, # 12, p. 4554 - 4557
[2] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 18, p. 5583 - 5591

4
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[ 58481-11-1 ]

Reference： [1] Journal of Organic Chemistry, 1997, vol. 62, # 10, p. 3158 - 3175

5
[ 773837-37-9 ]
[ 3783-38-8 ]
[ 94413-64-6 ]

Yield	Reaction Conditions	Operation in experiment
71.6%	With copper(l) iodide; N,N-Dimethylcarbamoyl chloride In acetonitrile at 90℃; for 7 h;	The formula (5) compound methyl isobutyl niacin-N-oxide 1.53g (10mmol), b a carbamic chloride (0.11 ml, 11mmol), sodium cyanide (0.98g, 20mmol), cuprous iodide 0.19g (1mmol) dissolved in 50 ml of acetonitrile, mixtures in 90 °C reaction under 7 hours, detecting reaction TLC (hexane/ethyl acetate = 1 the [...] 1), after the reaction, cooling to room temperature, add 20 ml water to stir reaction 5-30 minutes, removed the organic layer, the aqueous layer extracted with ethyl acetate three times, each 50 ml, combined with the organic layer, anhydrous sodium sulfate for drying, distilling solvent under reduced pressure, to obtain crude products, crude product using normal hexane/ethyl acetate = 4 the [...] 1 column chromatography, to obtain strawcoloured solid 1.16g, yield 71.6percent.

Reference： [1] Patent: CN104151297, 2016, B, . Location in patent: Paragraph 0039; 0040
[2] Journal of Medicinal Chemistry, 2009, vol. 52, # 10, p. 3385 - 3396

6
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[ 748101-41-9 ]
[ 94413-64-6 ]

Yield	Reaction Conditions	Operation in experiment
94%	With copper(l) iodide; N,N-Dimethylcarbamoyl chloride In acetonitrile at 80℃; for 5 h;	The formula (5) compound methyl isobutyl niacin-N-oxide 1.53g (10mmol), b a carbamic chloride (0.11 ml, 11mmol), zinc cyanide (1.40g, 12mmol), cuprous iodide 0.19g (1mmol) dissolved in 50 ml of acetonitrile, mixtures in 80 °C reaction under 5 hours, TLC detection reaction (hexane/ethyl acetate = 1 the [...] 1), after the reaction, cooling to room temperature, add 20 ml water to stir reaction 5-30 minutes, removed the organic layer, the aqueous layer extracted with ethyl acetate three times, each 50 ml, combined with the organic layer, anhydrous sodium sulfate for drying, distilling solvent under reduced pressure, to obtain crude products, crude product using normal hexane/ethyl acetate = 4 the [...] 1 column chromatography, to obtain strawcoloured solid 1.53g, yield 94percent, HPLC purity ( unitary method ): 97.7percent ; melting point: 107.5-108.7 °C.

Reference： [1] Patent: CN104151297, 2016, B, . Location in patent: Paragraph 0037; 0038

7
[ 3783-38-8 ]
[ 7677-24-9 ]
[ 94413-64-6 ]

Yield	Reaction Conditions	Operation in experiment
57%	at 50℃; Inert atmosphere	A mixture of 4-(methoxycarbonyl)pyridine 1-oxide (2 g, 13.06 mmol, 1.00 equiv), N,N-dimethylcarbamoyl chloride (6 g, 55.79 mmol, 4.27 equiv) and trimethylsilanecarbonitrile (6 g, 60.48 mmol, 4.63 equiv) in chloroform (60 g) was stirred overnight under nitrogen at 50 °C. The reaction mixture was concentrated under vacuum and the residue was purified on a silica gel column eluted with ethyl acetate/petroleum ether ( 1 :20) to give 1.2 g (57percent) of methyl 2-cyanopyridine-4-carboxylate as a light yellow solid. LC MS (Method F, ESI): RT= 1.22 min, m/z = 163.0 [M+H]⁺.
33%	With N,N-Dimethylcarbamoyl chloride In dichloromethane at 20℃; for 12 h;	Trimethylsilyl cyanide (3.8 g, 0.0386 mol) and dimethylcarbamyl chloride (5.0 g, 0.0483 mol) were added to a solution of methylisonicotinate N-oxide (5.0 g, 0.0322 mol) in dry CH₂Cl₂ (50 mL) at room temperature. The reaction mixture was stirred at room temperature for 12 h and then quenched with 10percent K₂CO₃ solution. The organic product was extracted with CH₂Cl₂ and the organic layer was washed with H₂O and brine, dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. The crude product was purified by flash column chromatography (silica 230-400 mesh, eluent 1-2percent MeOH in CH₂Cl₂) to afford methyl 2-cyanoisonicotinate (1.75 g, yield 33percent) as an off-white solid. ¹H NMR (400 MHz, DMSO-d₆) δ 8.97 - 8.95 (d, J = 5.0 Hz, 1 H), 8.41 (m, 1 H), 8.15 - 8.13 (dd, J = 4.8 Hz, 1.6 Hz, 1 H), 3.92 (s, 3H).

Reference： [1] Patent: WO2013/127268, 2013, A1, . Location in patent: Page/Page column 71; 72
[2] Patent: EP2533783, 2015, B1, . Location in patent: Paragraph 0425-0426
[3] Tetrahedron, 2018, vol. 74, # 25, p. 3165 - 3170

8
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[ 94413-64-6 ]

Yield	Reaction Conditions	Operation in experiment
70.8%	With copper(l) iodide; N,N-Dimethylcarbamoyl chloride In acetonitrile at 90℃; for 8 h;	The compound of formula (5), methyl isonicotinic acid-N-oxide, 1. 53 g (10 mmol), dimethylcarbamoyl chloride (0.1 mmol, 11 mmol), potassium cyanide (1.3 g, 20 mmol) and cuprous iodide 0.19 g (1 mmol) were dissolved in 50 ml of acetonitrile and mixed The reaction was carried out at 90 ° C for 8 hours. The reaction was monitored by TLC (n-hexane / ethyl acetate = 1: 1). After completion of the reaction, The reaction was stirred for 5 - 30 minutes at room temperature, the organic layer was discarded and the aqueous layer was extracted three times with 50 mL each of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure to give the crude product which was recrystallized from n-hexane / ethyl acetate = 4: 1 Column chromatography to give 1.15 g of a light yellow solid, yield 70.8

Reference： [1] Patent: CN104151297, 2016, B, . Location in patent: Paragraph 0041; 0042

9
[ 557-21-1 ]
[ 3783-38-8 ]
[ 94413-64-6 ]

Yield	Reaction Conditions	Operation in experiment
65%	With N,N-Dimethylcarbamoyl chloride In toluene for 6 h; Reflux; Inert atmosphere	A reaction mixture of 4-(methoxycarbonyl)pyridine-1-oxide²⁷ (0.20 g, 1.30 mmol), dimethylcarbamoyl chloride (DMCC, 0.12 mL, 1.30 mmol) and Zn(CN)₂ (0.23 g, 1.96 mmol) in toluene (15 mL) was heated to reflux under an argon atmosphere for 6 h. The reaction mixture was cooled to room temperature and deionised H₂O (10 mL) was added, and stirring was continued for 15 min. The organic layer was separated, washed with brine, dried over MgSO₄ and concentrated under reduced pressure to yield an orange solid (0.21 g, 65percent) which required no further purification. m.p. 100-103 °C; ν_max (KBr) 2958, 2852, 2237, 1726, 1441, 1397, 1298, 1209, 1116, 974, 934, 882, 869, 765 cm^-1; δ_H (300 MHz, CDCl₃) 8.90 (1 H, dd, J 4.9, 0.8 Hz, pyr-H), 8.24 (1 H, dd, J 1.5, 0.8 Hz, pyr-H), 8.07 (1 H, dd, J 4.9, 1.5 Hz, pyr-H), 4.01 (3 H, s, OCH₃); δ_C (75 MHz, CDCl₃) 162.6 (C=O), 151.0, 137.7, 133.8, 126.6, 125.0, 115.5 (CN), 52.3 (OCH₃); HRMS (ESI): [M+H]⁺, found 163.0509. C₈H₇N₂O₂ requires 163.0502. NMR data is in agreement with literature data.¹³

Reference： [1] Tetrahedron, 2016, vol. 72, # 51, p. 8470 - 8478

10
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[ 94413-64-6 ]

Reference： [1] Patent: EP1471065, 2004, A1, . Location in patent: Page 7

11
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[ 7677-24-9 ]
[ 79-44-7 ]
[ 94413-64-6 ]

Reference： [1] Patent: US6509361, 2003, B1,

12
[ 3783-38-8 ]
[ 577778-58-6 ]

Reference： [1] Patent: CN105367490, 2016, A,
[2] Patent: CN105348264, 2016, A,
[3] Patent: CN105348264, 2016, A,
[4] Patent: CN104151297, 2016, B,
[5] Patent: CN104151297, 2016, B,
[6] Patent: CN104151297, 2016, B,
[7] Patent: CN108250184, 2018, A,

[ 3783-38-8 ] Synthesis Path-Downstream 1~51

1
[ 2459-09-8 ]
[ 3783-38-8 ]

Yield	Reaction Conditions	Operation in experiment
99%	Stage #1: 4-pyridinecarboxylic acid, methyl ester With dihydrogen peroxide; methyltrioxorhenium(VII) In dichloromethane; lithium hydroxide monohydrate at 20℃; for 18h; Stage #2: With manganese(IV) oxide In dichloromethane at 20℃; for 2h;	I.19 To methyl isonicotinate (13.70 g, 100 mmol) and methyltrioxorhenium (125 mg, 0.5 mmol) in dichloromethane (40 ml_) was added dropwise 30% hydrogen peroxide/water (20 ml_, 200 mmol), and the mixture was stirred at ambient temperature for 18 h. Manganese dioxide (40 mg) was slowly added and vigorous bubbling occurred. After 2 h stirring at ambient temperature, water/brine (1 :1 ) was added, and the mixture was extracted with dichloromethane (3 X). The organic layer was dried over sodium sulfate, and concentrated to provide the title compound as a pale yellow solid (15.2 g, 99%): 1H NMR (400 MHz, DMSOd6) δ ppm 8.28 (d, J = 7.1 Hz, 2H), 7.82 (d, J = 7.1 Hz, 2H), 3.84 (s, 3H).
98%	With bis-trimethylsilanyl peroxide; per-rhenic acid In dichloromethane; lithium hydroxide monohydrate at 24℃; for 6h;
98%	With dihydrogen peroxide; methyltrioxorhenium(VII) In dichloromethane; lithium hydroxide monohydrate at 24℃; for 17h;

97%	With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 24h; Inert atmosphere;	10.2 4.10.2. 4-Methoxycarbonylpyridine N-Oxide Methyl isonicotinate (1.8 mL, 15.2 mmoles) and m-chloroperoxybenzoicacid (6.8 g, 30.4 mmoles) were dissolved in dry dichloromethane(150 mL) in a flame-dried flask. This reaction mixture wasstirred at room temperature for 24 h. The solution was concentratedunder reduced pressure, and the resulting residue was purifiedby chromatography on silica (1-4% v/v MeOH in acetone) toafford the title compound as a white solid (2.26 g, 97%) with mp118.1-121.3 C. 1H NMR (400 MHz, CDCl3, d): 8.20 (d, J = 4.0 Hz, 2H), 7.84 (d, J = 4.0 Hz, 2H), 3.90 (s, 3H); 13C NMR (100 MHz, CDCl3,d): 163.7, 139.4, 126.5, 126.4, 52.8; HRMS (ESI) m/z 154.0492[calc’d for C7H8NO3 (M+H)+ 154.0499].
95%	With dihydrogen peroxide; methyltrioxorhenium(VII) In dichloromethane; lithium hydroxide monohydrate at 20℃; Inert atmosphere;
95.2%	With dihydrogen peroxide; glacial acetic acid at 70℃;	isonicotinic acid methyl ester (20g, 145.8mmol) in the reaction bottle, acetic acid is added 120 ml, stirring, added to the reaction bottle 30% hydrogen peroxide (16.5g, 145 . 6mmol), 70 °C heating and stirring, 3h after, adding 30% hydrogen peroxide (11.6g, 102 . 3mmol), heating is continued stirring, after TLC monitoring reaction end, concentrated, water 50 ml, dichloromethane is used for 500 ml extraction, drying of the organic phase is concentrated, add hexane agitation washing, filtering, to obtain light yellow crystalline solid, 50 °C vacuum drying, be 21.26g, yield: 95.2%
95.2%	With dihydrogen peroxide In glacial acetic acid at 70℃;	1.1 Example 1 Preparation a isonicotinate N- oxide implementation: The isonicotinate (20g, 145.8mmol) placed in a reaction flask, acetic acid 120ml, stirring, to the reaction flaskWithin 30% hydrogen peroxide (16.5g, 145.6mmol), 70 heating and stirring, 3h later, additional 30% hydrogen peroxide (11.6g,102.3mmol), continued heating and stirring, TLC monitoring After the reaction was concentrated, water was added 50ml, extracted with dichloromethane 500ml,The organic phase was dried and concentrated, hexane added to stir washing, suction filtration to give a pale yellow crystalline solid, 50 deg.] C and dried in vacuo to afford 21.26g,Yield: 95.2%
93%	With dihydrogen peroxide; methyltrioxorhenium(VII) In dichloromethane at 24℃; for 12h; Inert atmosphere;
92%	With dihydrogen peroxide; glacial acetic acid at 70℃;
91%	Stage #1: 4-pyridinecarboxylic acid, methyl ester With 3-chloro-benzenecarboperoxoic acid In dichloromethane for 6h; Inert atmosphere; Reflux; Stage #2: With potassium carbonate In dichloromethane Inert atmosphere;
87%	With dihydrogen peroxide In methanol at 60℃; for 0.05h; Flow reactor; Schlenk technique; Green chemistry;	N-Oxidation of 3-Methylpyridine; Typical Procedures General procedure: Continuous flow process: TS-1 catalyst (955 mg) was prepared to 40- 60 mesh of particle, which was filled in a packed-bed microreactor. A liquid phase plunger pump was then connected to the column, and the parameters were set with a 0.6 mL/min flow rate. The reaction mixture of 3-methylpyridine (1a; 0.25 mol/L) and H2O2 (0.275 mol/L) with CH3OH as the solvent was prepared, which connected with the plunger pump. Then the micro stainless steel column was put into a 60 °C water bath, and the pump was started. After a few minutes, 2.0 mL of the reaction mixture was collected. Next, CH3OH in the solution was removed by vacuum rotary evaporation, and the residue was purified by flash column chromatography (silica gel) to give the desired product 2a and unreacted 1a. Another 2.0 mL of the reaction mixture was measured for the calculation method for XH2O2 and UH2O2 by KMnO4 titration method.
78%	With 3-chloro-benzenecarboperoxoic acid In dichloromethane	11.1 Step 1 . 4-(Methoxycarbonyl)pyridine 1 -oxide. A solution of methyl pyridine- 4-carboxylate (3 g, 21 .88 mmol, 1 .00 equiv) and m-chloroperbenzoic acid (5 g, 28.97 mmol, 1 .32 equiv) in DCM (30 mL) was stirred overnight at ty. The precipitated product was collected by filtration to give 2.6 g (78%) of 4- (methoxycarbonyl)pyridine 1 -oxide as an off-white solid. LC/MS (Method J, ESI): RT= 0.89 min, m/z = 1 4.0 [M+H]+ .
70%	With dihydrogen peroxide; glacial acetic acid
65%	With dihydrogen peroxide In lithium hydroxide monohydrate; glacial acetic acid	31.1 Step 1 Step 1 Preparation of Methyl Isonicotinate N-Oxide: To a solution of hydrogen peroxide (43 mL) in 250 mL of acetic acid was added methyl isonicotinate. The reaction mixture was stirred at 80° C. overnight (about eighteen hours). The solution was concentrated to about 50 mL, water was added and the mixture was saturated with sodium carbonate. The aqueous phase was extracted with methylene chloride. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated and trituated with hexane. The resulting precipitate was filtered and air-dried to give 24.5 g (65% yield) of product as a white solid: mp: 118-120° C.
46%	With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 3h; Sealed tube;
	With Perbenzoic acid In 1,4-dioxane; lithium hydroxide monohydrate at 20℃; other temp. (25, 30 deg C); ΔS(excit.);
	With dihydrogen peroxide; glacial acetic acid
	Stage #1: 4-pyridinecarboxylic acid, methyl ester With dihydrogen peroxide In dichloromethane at 20℃; Stage #2: In dichloromethane at 20℃; for 1h;	51 According to Scheme 52, to a solution of compound 82 (13.7 g, 0.1 mol) in CH2C12 at room temperature was added H202 (20 mL, 50% v/v, Aldrich), and methyltrioxorhennium (MTO, 250 mg, 1 mmol, Aldrich). The resulting mixture was stirred at room temperature for 12 h. Mn02 (25 mg) was added and the mixture was left at room temperature for 1 h or until there is no more gas release (02) from the mixture. The organic layer of the mixture was separated, and the aqueous layer was extracted with CH2C12 (100 mL). The combined organic layers were dried over Na2S04, filtered, and concentrated to dryness. The residue was washed with 30% EtOAc/Hexane and the solid was dried under vacuum to give compound 83 (12.7 g, 84 mmol).
	With 3-chloro-benzenecarboperoxoic acid In acetonitrile at 95℃; Flow reactor;	Flow synthesis of methyl 2-cyanoisonicotinate (4) A solution of methyl 4-carboxypyridine (1M in MeCN) and a solution of mCPBA (1M in MeCN) were flowed via a T-mixer into a 10mL flow reactor at 95°C at a rate of 1.0mL per minute (Scheme 3). The solution of methyl 4-carboxypyridine N-oxide exiting the first reactor was combined with TMSCN/NEt3 (1:2.5, 1M in MeCN) via a second T-mixer. This solution was flowed into a 5mL reactor at 150°C at a rate of 0.2mL per minute. The solution exiting the reactor was collected and the solvent evaporated to provide methyl 2-cyanoisonicotinate (4).
	With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 18h;
	Stage #1: 4-pyridinecarboxylic acid, methyl ester With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0 - 20℃; for 6h; Stage #2: With triphenylphosphine In dichloromethane at 20℃; for 4h;

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2009/76387, 2009, A1 Location in patent: Page/Page column 29
[2]Coperet, Christophe; Adolfsson, Hans; Chiang, Jay P.; Yudin, Andrei K.; Sharpless, K. Barry [Tetrahedron Letters, 1998, vol. 39, # 8, p. 761 - 764]
[3]Coperet, Christophe; Adolfsson, Hans; Khuong, Tinh-Alfredo V.; Yudin, Andrei K.; Sharpless, K. Barry [Journal of Organic Chemistry, 1998, vol. 63, # 5, p. 1740 - 1741]
[4]Vasta, James D.; Raines, Ronald T. [Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 13, p. 3081 - 3090]
[5]Campeau, Louis-Charles; Stuart, David R.; Leclerc, Jean-Philippe; Bertrand-Laperle, Megan; Villemure, Elisia; et al. [Journal of the American Chemical Society, 2009, vol. 131, p. 3291 - 3306]
[6]Current Patent Assignee: CHINA NATIONAL PHARMACEUTICAL GROUP CORPORATION - CN105367490, 2016, A Location in patent: Paragraph 0031; 0032; 0033
[7]Current Patent Assignee: CHINA NATIONAL PHARMACEUTICAL GROUP CORPORATION - CN105348264, 2016, A Location in patent: Paragraph 0023; 0025
[8]Ma, Xiaoshen; Dang, Hester; Rose, John A.; Rablen, Paul; Herzon, Seth B. [Journal of the American Chemical Society, 2017, vol. 139, # 16, p. 5998 - 6007]
[9]Gu, Yifan; Lewis, Jared C.; Liu, Bingqing; Sahoo, Dipankar; Zubi, Yasmine S. [Chemical Science, 2022, vol. 13, # 5, p. 1459 - 1468]
[10]Smirnov, Vladimir O.; Maslov, Anton S.; Kokorekin, Vladimir A.; Korlyukov, Alexander A.; Dilman, Alexander D. [Chemical Communications, 2018, vol. 54, # 18, p. 2236 - 2239]
[11]Chen, Siyuan; Yang, Shanxiu; Wang, Hao; Niu, Yanning; Zhang, Zhang; Qian, Bo [Synthesis, 2022]
[12]Current Patent Assignee: FORMA THERAPEUTICS, INC.; ROCHE HOLDING AG - WO2013/127268, 2013, A1 Location in patent: Page/Page column 71
[13]Taylor, Scott D.; Mirzaei, Farzad; Sharifi, Ali; Bearne, Stephen L. [Journal of Organic Chemistry, 2006, vol. 71, # 25, p. 9420 - 9430]
[14]Current Patent Assignee: PFIZER INC - US6509361, 2003, B1
[15]Sevov, Christo S.; Brooner, Rachel E. M.; Chénard, Etienne; Assary, Rajeev S.; Moore, Jeffrey S.; Rodríguez-López, Joaquín; Sanford, Melanie S. [Journal of the American Chemical Society, 2015, vol. 137, # 45, p. 14465 - 14472]
[16]Lohkov, R.E. [Chemistry of Heterocyclic Compounds, 1980, vol. 16, # 3, p. 264 - 271][Khimiya Geterotsiklicheskikh Soedinenii, 1980, vol. 16, # 3, p. 354 - 362]
[17]Yale et al. [Journal of the American Chemical Society, 1953, vol. 75, p. 1933,1934] Bixler; Niemann [Journal of the American Chemical Society, 1958, vol. 80, p. 2716,2718]
[18]Current Patent Assignee: PURDUE PHARMA L.P. - WO2012/35421, 2012, A2 Location in patent: Page/Page column 237-238
[19]Dhanya, Raveendra Panickar; Herath, Ananda; Sheffler, Douglas J.; Cosford, Nicholas D.P. [Tetrahedron, 2018, vol. 74, # 25, p. 3165 - 3170]
[20]Jeon, Jinwon; He, Yu-Tao; Shin, Sanghoon; Hong, Sungwoo [Angewandte Chemie - International Edition, 2020, vol. 59, # 1, p. 281 - 285][Angew. Chem., 2020, vol. 132, # 1, p. 287 - 291,5]
[21]Hu, Qiang; Yu, Wan-Lei; Luo, Yong-Chun; Hu, Xiu-Qin; Xu, Peng-Fei [Journal of Organic Chemistry, 2022, vol. 87, # 2, p. 1493 - 1501]

2
[ 3783-38-8 ]
[ 6975-73-1 ]

Yield	Reaction Conditions	Operation in experiment
96.5%	With hydrazine hydrate monohydrate In methanol at 60℃; for 2h; Inert atmosphere;	the isonicotinic acid methyl ester N-oxide (20g, 130.6mmol) in the reaction bottle, by adding methanol 200 ml, after stirring to complete dissolution, dripping 85% hydrazine hydrate (14.5g, 246 . 2mmol), nitrogen protection, 60 °C heating reaction 2h, cooling to room temperature, by adding isopropyl ether 50 ml stirring, filtering, getting white solid, 45 °C vacuum drying, dry weight 19.3g, yield: 96.5%.
96.5%	With hydrazine hydrate monohydrate In methanol at 60℃; for 2h; Inert atmosphere;	2.1 Example 2 Preparation N- oxide isoniazide embodiment: 1) Will isonicotinate N- oxide (20g, 130.6mmol) placed in a reaction flask, methanol was added to 200ml, stirring until the whole After the solution was added dropwise 85% hydrazine hydrate (14.5g, 246.2mmol), nitrogen, the reaction was heated 60 deg.] C 2h, cooled to room temperature,Was stirred into 50ml of isopropyl ether, suction filtered, washed with isopropyl ether to give an off-white solid, 45 dried in vacuo, 19.3g of dry weight, yield:96.5%.
95.6%	With hydrazine hydrate monohydrate In methanol at 50℃; for 8h; Large scale;	2.1 1)Isonicotinic acid hydrazide oxynitridePreparation 3000g of methyl nicotinate oxynitride, 2000g of hydrazine hydrate (85%),30L of methanol was put into a 50L glass jacketed reaction kettle, and the temperature was raised to 50 ° C under stirring.The reaction was carried out for 8 h, the temperature was lowered to below 20 ° C, filtered, and the filter cake was washed with 6000 ml of cold methanol.After drying at 55 ° C for 12 h under vacuum, 2870 g of a white solid was obtained, yield 95.6%.

92.4%	With hydrazine hydrate monohydrate In methanol at 68℃; for 6h;	1.3; 4.3 (3) Preparation of Intermediate 3: Intermediate 2 (12.0 g, 78.4 mmol, 1.0 eq) was added to methanol (80 mL), hydrazine hydrate (80% content, 5.88 g, 94.0 mmol, 1.2 eq) was added, and the reflux reaction temperature was controlled to be 68 °C, and the reflux reaction was carried out. 6h. TLC showed that the raw material was completely consumed, the temperature was cooled to 4°C in an ice-salt bath, crystallized for 2 h, filtered, and the filter cake was rinsed with a small amount of methanol (20 mL). The obtained solid was dried by blasting at 45° C. for 4 hours to obtain 11.09 g of the product with a yield of 92.4%.
	With methanol; hydrazine hydrate monohydrate
	With ethanol; hydrazine hydrate monohydrate
	With hydrazine hydrate monohydrate

Reference： [1]Current Patent Assignee: CHINA NATIONAL PHARMACEUTICAL GROUP CORPORATION - CN105367490, 2016, A Location in patent: Paragraph 0031; 0035; 0036
[2]Current Patent Assignee: CHINA NATIONAL PHARMACEUTICAL GROUP CORPORATION - CN105348264, 2016, A Location in patent: Paragraph 0023; 0027; 0028
[3]Current Patent Assignee: BEIJING CHENGJI PHARMACEUTICAL - CN108250184, 2018, A Location in patent: Paragraph 0035; 0044; 0045; 0046
[4]Current Patent Assignee: SHANDONG UNIVERSITY - CN113801099, 2021, A Location in patent: Paragraph 0061; 0069-0071; 0091-0094
[5]Yale et al. [Journal of the American Chemical Society, 1953, vol. 75, p. 1933,1934] Bixler; Niemann [Journal of the American Chemical Society, 1958, vol. 80, p. 2716,2718]
[6]Yale et al. [Journal of the American Chemical Society, 1953, vol. 75, p. 1933,1934] Bixler; Niemann [Journal of the American Chemical Society, 1958, vol. 80, p. 2716,2718]
[7]Yale et al. [Journal of the American Chemical Society, 1953, vol. 75, p. 1933,1934] Bixler; Niemann [Journal of the American Chemical Society, 1958, vol. 80, p. 2716,2718]

3
[ 3783-38-8 ]
[ 2459-09-8 ]

Yield	Reaction Conditions	Operation in experiment
98%	With ammonium formate In methanol for 0.0166667h; Ambient temperature;
98%	With sodium hypophosphite In acetic acid at 60℃; for 1h;
97%	With ammonium formate; silica gel; zinc In methanol at 20℃; for 0.166667h; chemoselective reaction;

95%	With titanium tetrachloride; sodium iodide In acetonitrile at 20℃; for 0.0333333h;
91%	With ammonium formate In methanol at 25℃; for 1h;
87%	With polymethylhydrosiloxane In ethanol at 20℃;
78%	With ammonium formate; zinc In methanol for 3h; Heating;
66%	With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate In dichloromethane at 31℃; for 16h; Sealed tube; Irradiation;
	With p-toluenesulfonylanhydride In chloroform at 0℃;	4.2 Synthesis of methyl 2-aminoisonicotinate (15) To an ice-cooled solution of the above product (4-(methoxycarbonyl)pyridine 1-oxide, 300 mg, 1.96 mmol) in CHCl3 was added tosyl anhydride (2877 mg, 8.82 mmol) and the mixture was stirred for 5 min. Next, t-BuNH2 (1.24 ml, 11.8 mmol) was added dropwise via syringe to the activated N-oxide while maintaining the reaction temperature below 5 °C. The reaction was monitored by TLC and until complete consumption of starting material (∼30 min) was observed. TFA (10.0 ml, 131 mmol) was added to the reaction mixture and the reaction was stirred at 70 °C overnight. The mixture was diluted with water (5 mL) and DCM (10 mL) and carefully neutralized with saturated NaHCO3. The aqueous layer was extracted using DCM (4 × 10 mL). The combined organic layers were washed once with brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography using a CombiFlash instrument and a solvent gradient from 100% hexanes to 100% EtOAc and then to 25% MeOH in EtOAc (all eluents contained 0.1% triethylamine) to yield the desired methyl 2-aminoisonicotinate product obtained as reddish/brown crystals (153.3 mg, 51%).

Reference： [1]Balicki, Roman [Synthesis, 1989, # 8, p. 645 - 646]
[2]Balicki, Roman; Kaczmarek, Lukasz [Gazzetta Chimica Italiana, 1994, vol. 124, # 9, p. 385 - 386]
[3]Rajesh [Journal of Heterocyclic Chemistry, 2018, vol. 55, # 2, p. 486 - 491]
[4]Balicki, Roman [Chemische Berichte, 1990, vol. 123, p. 647 - 649]
[5]Balicki, Roman; Maciejewski, Grzegorz [Synthetic Communications, 2002, vol. 32, # 11, p. 1681 - 1683]
[6]Chandrasekhar; Reddy, Ch. Raji; Rao, R. Jagadeeshwar; Rao, J. Madhusudana [Synlett, 2002, # 2, p. 349 - 351]
[7]Balicki, Roman; Cybulski, Marcin; Maciejewski, Grzegorz [Synthetic Communications, 2003, vol. 33, # 23, p. 4137 - 4141]
[8]Cardinale, Luana; Jacobi Von Wangelin, Axel; Konev, Mikhail O. [Organic Letters, 2020]
[9]De Schutter, Joris W.; Shaw, Joseph; Lin, Yih-Shyan; Tsantrizos, Youla S. [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 18, p. 5583 - 5591]

4
[ 3783-38-8 ]
[ 58481-11-1 ]

Yield	Reaction Conditions	Operation in experiment
95%	With trichlorophosphate In chloroform for 12h; Heating;

Reference： [1]Amat, Mercedes; Hadida, Sabine; Pshenichnyi, Grigorii; Bosch, Joan [Journal of Organic Chemistry, 1997, vol. 62, # 10, p. 3158 - 3175]

5
[ 3783-38-8 ]
[ 19075-68-4 ]

Yield	Reaction Conditions	Operation in experiment
24%	With copper(II) sulfate In water Irradiation;
	With copper(II) sulfate In water Irradiation;

Reference： [1]Campbell, Shirley E.; Comer, Murray C.; Derbyshire, Paul A.; Despinoy, Xavier L. M.; McNab, Hamish; Morrison, Roderick; Sommerville, Craig C.; Thornley, Craig [Journal of the Chemical Society. Perkin transactions I, 1997, # 15, p. 2195 - 2202]
[2]Despinoy; Harris; McNab; Parsons; Withell [Acta Crystallographica, Section C: Crystal Structure Communications, 1998, vol. 54, # pt 2, p. 231 - 233]

6
[ 3783-38-8 ]
[ 89937-77-9 ]

Yield	Reaction Conditions	Operation in experiment
41%	With acetic anhydride Heating;
13%	Stage #1: methyl isonicotinate N-oxide With acetic anhydride for 16h; Heating / reflux; Stage #2: With methanol for 0.5h; Heating / reflux;	7.a Example 7; 1-MethyI-2-oxo-l,2-dihydro-pyridine-4-carboxyIic acid [5-(3-pyridin-3-yl-5-trifluoromethyl-pyrazol-l-yl)-pyridin-2-yl]-amide; Step a; A solution of methyl isonicotinate-iV-oxide (3 g, 19.59 nxmol) in acetic anhydride (30 mJL) is heated at reflux for 16 hours. The reaction mixture is allowed to cool to room temperature, concentrated under vacuo, diluted with methanol and with celite added, the mixture is heated at reflux for 30 min. The reaction mixture is filtered, reduced under vacuo and triturated with methanol to give 2-hydroxy-isonicotinic acid methyl ester (400 mg, 13 %).

Reference： [1]Taylor, Scott D.; Mirzaei, Farzad; Sharifi, Ali; Bearne, Stephen L. [Journal of Organic Chemistry, 2006, vol. 71, # 25, p. 9420 - 9430]
[2]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - WO2007/67836, 2007, A2 Location in patent: Page/Page column 102

7
[ 67-56-1 ]
[ 13602-12-5 ]
[ 3783-38-8 ]

Yield	Reaction Conditions	Operation in experiment
97%	With diazomethyl-trimethyl-silane In hexane at 0℃; for 1h;
91.2%	With sulfuric acid at 64℃; for 8h;	1.2; 3.2 (2) Preparation of Intermediate 2: Intermediate 1 (10.0 g, 71.9 mmol, 1.0 eq) was dissolved in methanol (80 mL), concentrated sulfuric acid (5.0 g) was added dropwise, the reflux reaction temperature was controlled to be 64°C, and the reflux reaction was performed for 8 h. TLC showed that a small amount of raw materials remained and stopped. Heating, cooling in an ice-water bath, adding sodium carbonate solid in batches, controlling the temperature not to exceed 20 °C, adjusting the pH to 7, filtering, rinsing the filter cake twice with a small amount of methanol, and evaporating the methanol to dryness under reduced pressure at 45 °C, the obtained solid It was dissolved in dichloromethane (100 mL), washed with 15 mL of 5% sodium carbonate aqueous solution, the dichloromethane phase was separated, dried with a little sodium sulfate, and evaporated to dryness under reduced pressure at 45 ° C to obtain 10.10 g of the product, yield : 91.2%.
72%	With thionyl chloride at 20℃; for 2h;

45%

With sulfuric acid In toluene Reflux; Dean-Stark;

4.2 Synthesis of methyl 2-aminoisonicotinate (15) Isonicotinic acid N-oxide (3.00 g, 21.6 mmol) was dissolved in 20 ml 1:1 methanol/toluene, a catalytic amount H2SO4 was added and the flask was equipped with a Dean Stark trap filled with toluene. The mixture was refluxed overnight. The reaction was terminated by cooling in an ice bath, and neutralized with satd. sodium carbonate. The solution was extracted using (5 × 20 ml) DCM; the organic phases were combined, washed with brine, dried with MgSO4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography using a CombiFlash instrument and a solvent gradient from 100% hexanes to 100% EtOAc to give 4-(methoxycarbonyl)pyridine 1-oxide as a white powder (1.46 g, 45%). 1H NMR (300 MHz, CDCl3) δ 8.24-8.16 (m, 2H), 7.93-7.79 (m, 2H), 3.94 (s, 3H).

Reference： [1]Yin, Jingjun; Xiang, Bangping; Huffman, Mark A.; Raab, Conrad E.; Davies, Ian W. [Journal of Organic Chemistry, 2007, vol. 72, # 12, p. 4554 - 4557]
[2]Current Patent Assignee: SHANDONG UNIVERSITY - CN113801099, 2021, A Location in patent: Paragraph 0061; 0066-0068; 0087-0090
[3]Rassadin, Valentin A.; Zimin, Dmitry P.; Raskil'dina, Gulnara Z.; Ivanov, Alexander Yu.; Boyarskiy, Vadim P.; Zlotskii, Semen S.; Kukushkin, Vadim Yu. [Green Chemistry, 2016, vol. 18, # 24, p. 6630 - 6636]
[4]De Schutter, Joris W.; Shaw, Joseph; Lin, Yih-Shyan; Tsantrizos, Youla S. [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 18, p. 5583 - 5591]

8
[ 3783-38-8 ]
[ 6937-03-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: Ts₂O / various solvent(s) / 0.25 h 2: TFA / various solvent(s) / 70 °C
	Multi-step reaction with 3 steps 1: p-toluenesulfonylanhydride / chloroform / 5 min / 0 °C 2: chloroform / 0.5 h / 5 °C 3: trifluoroacetic acid / chloroform / 70 °C

Reference： [1]Yin, Jingjun; Xiang, Bangping; Huffman, Mark A.; Raab, Conrad E.; Davies, Ian W. [Journal of Organic Chemistry, 2007, vol. 72, # 12, p. 4554 - 4557]
[2]De Schutter, Joris W.; Shaw, Joseph; Lin, Yih-Shyan; Tsantrizos, Youla S. [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 18, p. 5583 - 5591]

9
[ 13602-12-5 ]
[ 16357-59-8 ]
[ 3783-38-8 ]

Yield	Reaction Conditions	Operation in experiment
		Example 12. 5-(2-Cyano-4-pyridyl)-3-(4-pyridyl)-1,2,4-triazole1) Production of methyl isonicotinate N-oxide 13.9 g of isonicotinic acid N-oxide was added to 209 ml of methylene chloride, 29.7 g of 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline was further added thereto, and the mixture was stirred under argon atmosphere at room temperature for one hour. 32.1 g of methanol was added to this mixture, which was stirred at room temperature for 17 hours. After the solvent was evaporated under reduced pressure, the residue was subjected to silica gel column chromatography. Chloroform-acetone (3:1) was used as an eluent to yield 11.1g of a white powder.1H-NMR(CDCl3) delta ppm: 3.95(3H, s), 7.88(2H, d, J=7.25Hz), 8.22(2H, J=7.25Hz)

Reference： [1]Patent: EP1471065,2004,A1 .Location in patent: Page 7

10
[ 3783-38-8 ]
[ 94413-64-6 ]

Yield	Reaction Conditions	Operation in experiment
	With trimethylsilyl cyanide; triethylamine; In acetonitrile; for 16h;reflux;	2) Production of methyl 2-cyanoisonicotinate 11.1 g of the crystal obtained in 1) was dissolved in 170 ml of acetonitrile, 14.6 g of triethylamine and 21.5 g of trimethylsilylnitrile were added thereto, and the mixture was refluxed under argon atmosphere for 16 hours. After the solvent was evaporated under reduced pressure, the residue was subjected to silica gel column chromatography. Chloroform-acetone (95:5) was used as an eluent to yield 8.44 g of a pale yellow powder.1H-NMR(CDCl3) delta ppm: 4.01(3H, s), 8.08(1H, d, J=5.45Hz), 8.24(1H, s), 8.90(1H, d, J=5.45 Hz)

Reference： [1]Patent: EP1471065,2004,A1 .Location in patent: Page 7

11
[ 3783-38-8 ]
[ 7677-24-9 ]
[ 79-44-7 ]
[ 94413-64-6 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In dichloromethane;	Step 2 Preparation of Methyl 2-Cyanoisonicotinate: To a solution of methyl isonicotinate N-oxide (20.0 g, 0.26 mol) in 200 mL of methylene chloride was added trimethylsilyl cyanide (16.1 g, 0.32 mol), followed by a solution of dimethylcarbamyl chloride (17.82 g, 0.32 mol) in 50 mL of methylene chloride at room temperature. The reaction mixture was stirred overnight (about eighteen hours) and then treated with 500 mL of 10percent potassium carbonate solution. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated to 15.2 g of crude product as a brown solid, which was used without further purification.

Reference： [1]Patent: US6509361,2003,B1

12
[ 3783-38-8 ]
[ 108-24-7 ]
[ 1160938-15-7 ]

Yield	Reaction Conditions	Operation in experiment
26%	at 14℃; for 6h;	I.20 A mixture of methyl isonicotinate λ/-oxide (15.0 g, 97.9 mmol) and acetic anhydride (150 ml_) was heated to 140C for 6 h. The mixture was concentrated, and the residue was heated to 6O0C with methanol and activated charcoal (Darco G-60) for 15 min, then filtered through a bed of Celite. The filtrate was concentrated, and the residue was triturated with diethyl ether. The solid was filtered to provide recovered methyl isonicotinate λ/-oxide (4.0 g, 26%). The filtrate was washed with saturated aqueous sodium bicarbonate, brine, and dried over sodium sulfate. The solution was concentrated and purified by column chromatography on silica gel, eluting with 2% methanokdichloromethane, to afford the title compound as a pale yellow solid (5.0 g, 26%): 1H NMR (400 MHz, DMSOd6) δ ppm 8.56 (d, J = 5.0 Hz, 1 H), 7.77 (d, J = 5.0 Hz, 1 H), 7.65 (s, 1 H), 3.89 (s, 3H), 2.30 (s, 3H).

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2009/76387, 2009, A1 Location in patent: Page/Page column 29

13
[ 104-92-7 ]
[ 3783-38-8 ]
[ 1127561-75-4 ]

Yield	Reaction Conditions	Operation in experiment
88%	With palladium diacetate; potassium carbonate; tri tert-butylphosphoniumtetrafluoroborate In toluene at 110℃; Inert atmosphere;

Reference： [1]Campeau, Louis-Charles; Stuart, David R.; Leclerc, Jean-Philippe; Bertrand-Laperle, Megan; Villemure, Elisia; et al. [Journal of the American Chemical Society, 2009, vol. 131, p. 3291 - 3306]

14
[ 3783-38-8 ]
[ 556-96-7 ]
[ 1127561-73-2 ]

Yield	Reaction Conditions	Operation in experiment
97%	With palladium diacetate; potassium carbonate; tri tert-butylphosphoniumtetrafluoroborate In toluene at 110℃; Inert atmosphere;
97%	With palladium diacetate; potassium carbonate; tri tert-butylphosphoniumtetrafluoroborate In toluene at 110℃;

15
[ 3783-38-8 ]
[ 99747-74-7 ]
[ 1174000-47-5 ]

Yield	Reaction Conditions	Operation in experiment
59%	With rubidium carbonate; palladium diacetate; tricyclohexylphosphine tetrafluoroborate; Trimethylacetic acid In toluene at 100℃; for 15h; Inert atmosphere;

Reference： [1]Location in patent: experimental part Schipper, Derek J.; El-Salfiti, Mohamed; Whipp, Christopher J.; Fagnou, Keith [Tetrahedron, 2009, vol. 65, # 26, p. 4977 - 4983]

16
[ 3783-38-8 ]
[ 146397-87-7 ]
[ 1174000-61-3 ]

Reference： [1]Tetrahedron,2009,vol. 65,p. 4977 - 4983

17
[ 773837-37-9 ]
[ 3783-38-8 ]
[ 94413-64-6 ]

Yield	Reaction Conditions	Operation in experiment
71.6%	With copper(l) iodide; N,N-Dimethylcarbamoyl chloride; In acetonitrile; at 90℃; for 7h;	The formula (5) compound methyl isobutyl niacin-N-oxide 1.53g (10mmol), b a carbamic chloride (0.11 ml, 11mmol), sodium cyanide (0.98g, 20mmol), cuprous iodide 0.19g (1mmol) dissolved in 50 ml of acetonitrile, mixtures in 90 °C reaction under 7 hours, detecting reaction TLC (hexane/ethyl acetate = 1 the [...] 1), after the reaction, cooling to room temperature, add 20 ml water to stir reaction 5-30 minutes, removed the organic layer, the aqueous layer extracted with ethyl acetate three times, each 50 ml, combined with the organic layer, anhydrous sodium sulfate for drying, distilling solvent under reduced pressure, to obtain crude products, crude product using normal hexane/ethyl acetate = 4 the [...] 1 column chromatography, to obtain strawcoloured solid 1.16g, yield 71.6percent.

Reference： [1]Patent: CN104151297,2016,B .Location in patent: Paragraph 0039; 0040
[2]Journal of Medicinal Chemistry,2009,vol. 52,p. 3385 - 3396

18
[ 3783-38-8 ]
[ 100-59-4 ]
[ 4634-14-4 ]

Yield	Reaction Conditions	Operation in experiment
63%	Stage #1: methyl isonicotinate N-oxide; phenylmagnesium chloride With methanol In tetrahydrofuran at -78 - 20℃; Inert atmosphere; Stage #2: With trifluoroacetic anhydride In tetrahydrofuran at 20℃; for 0.333333h; regioselective reaction;
63%	Stage #1: methyl isonicotinate N-oxide; phenylmagnesium chloride In tetrahydrofuran at -40℃; Stage #2: With methanol; trifluoroacetic anhydride In tetrahydrofuran at -40 - 20℃;

Reference： [1]Andersson, Hans; Sainte-Luce Banchelin, Thomas; Das, Sajal; Olsson, Roger; Almqvist, Fredrik [Chemical Communications, 2010, vol. 46, # 19, p. 3384 - 3386]
[2]Wang, Youliang; Zhang, Liming [Synthesis, 2015, vol. 46, # 4]

19
[ 3783-38-8 ]
[ 98-54-4 ]
[ 1274856-71-1 ]

Yield	Reaction Conditions	Operation in experiment
83%	With N-ethyl-N,N-diisopropylamine; bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate In tetrahydrofuran at 25℃; for 15h;

Reference： [1]Londregan, Allyn T.; Jennings, Sandra; Wei, Liuqing [Organic Letters, 2011, vol. 13, # 7, p. 1840 - 1843]

20
[ 3783-38-8 ]
[ 5183-78-8 ]
[ 1274856-70-0 ]

Yield	Reaction Conditions	Operation in experiment
53%	With N-ethyl-N,N-diisopropylamine; bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate In dichloromethane at 25℃; for 15h;

Reference： [1]Londregan, Allyn T.; Jennings, Sandra; Wei, Liuqing [Organic Letters, 2011, vol. 13, # 7, p. 1840 - 1843]

21
[ 109-04-6 ]
[ 3783-38-8 ]
[ 1355019-38-3 ]

Yield	Reaction Conditions	Operation in experiment
54%	With palladium diacetate; potassium carbonate; tri tert-butylphosphoniumtetrafluoroborate In toluene at 20 - 120℃;
47%	Stage #1: 2-bromo-pyridine; methyl isonicotinate N-oxide With zinc chloride-2,2,6,6-tetramethylpiperidin-1-ide lithium chloride complex In tetrahydrofuran Inert atmosphere; Stage #2: With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ In tetrahydrofuran at 60℃; for 18h; Inert atmosphere; regioselective reaction;

Reference： [1]Gu, Yifan; Lewis, Jared C.; Liu, Bingqing; Sahoo, Dipankar; Zubi, Yasmine S. [Chemical Science, 2022, vol. 13, # 5, p. 1459 - 1468]
[2]Gosselin, Francis; Savage, Scott J.; Blaquiere, Nicole; Staben, Steven T. [Organic Letters, 2012, vol. 14, # 3, p. 862 - 865]

22
[ 5315-25-3 ]
[ 3783-38-8 ]
[ 1355019-39-4 ]

Yield	Reaction Conditions	Operation in experiment
52%	Stage #1: 2-bromo-6-methylpyridine; methyl isonicotinate N-oxide With zinc chloride-2,2,6,6-tetramethylpiperidin-1-ide lithium chloride complex In tetrahydrofuran Inert atmosphere; Stage #2: With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ In tetrahydrofuran at 60℃; for 18h; Inert atmosphere; regioselective reaction;

Reference： [1]Gosselin, Francis; Savage, Scott J.; Blaquiere, Nicole; Staben, Steven T. [Organic Letters, 2012, vol. 14, # 3, p. 862 - 865]

23
[ 3783-38-8 ]
[ 4595-60-2 ]
[ 1355019-40-7 ]

Yield	Reaction Conditions	Operation in experiment
31%	Stage #1: methyl isonicotinate N-oxide; 2-bromopyrimidine With zinc chloride-2,2,6,6-tetramethylpiperidin-1-ide lithium chloride complex In tetrahydrofuran Inert atmosphere; Stage #2: With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ In tetrahydrofuran at 60℃; for 18h; Inert atmosphere; regioselective reaction;

Reference： [1]Gosselin, Francis; Savage, Scott J.; Blaquiere, Nicole; Staben, Steven T. [Organic Letters, 2012, vol. 14, # 3, p. 862 - 865]

24
[ 3783-38-8 ]
[ 55102-99-3 ]
[ 1367127-21-6 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; tri tert-butylphosphoniumtetrafluoroborate In toluene at 100℃;	51 A suspension of compound 83 (576 mg, 3.76 mmol), compound 14 (500 mg, 1.9 mmol), Pd(OAc)2 (43 mg, 0.19 mmol, Aldrich), P(tBu)3HBF4 (165 mg, 0.57 mmol, Aldrich) and K2C03 (524 mg, 3.8 mmol) in toluene (6 mL) was heated to reflux for 24 h. After cooling to room temperature, the reaction mixture was purified without work-up by column chromatography (40 g silica, EtOAc) to give compound 84 (265 mg, 0.78 mmol).

Reference： [1]Current Patent Assignee: PURDUE PHARMA L.P. - WO2012/35421, 2012, A2 Location in patent: Page/Page column 238

25
[ 3783-38-8 ]
[ 7677-24-9 ]
[ 94413-64-6 ]

Yield	Reaction Conditions	Operation in experiment
57%	In chloroform; at 50℃;Inert atmosphere;	A mixture of 4-(methoxycarbonyl)pyridine 1-oxide (2 g, 13.06 mmol, 1.00 equiv), N,N-dimethylcarbamoyl chloride (6 g, 55.79 mmol, 4.27 equiv) and trimethylsilanecarbonitrile (6 g, 60.48 mmol, 4.63 equiv) in chloroform (60 g) was stirred overnight under nitrogen at 50 °C. The reaction mixture was concentrated under vacuum and the residue was purified on a silica gel column eluted with ethyl acetate/petroleum ether ( 1 :20) to give 1.2 g (57percent) of methyl 2-cyanopyridine-4-carboxylate as a light yellow solid. LC MS (Method F, ESI): RT= 1.22 min, m/z = 163.0 [M+H]+.
33%	With N,N-Dimethylcarbamoyl chloride; In dichloromethane; at 20℃; for 12h;	Trimethylsilyl cyanide (3.8 g, 0.0386 mol) and dimethylcarbamyl chloride (5.0 g, 0.0483 mol) were added to a solution of methylisonicotinate N-oxide (5.0 g, 0.0322 mol) in dry CH2Cl2 (50 mL) at room temperature. The reaction mixture was stirred at room temperature for 12 h and then quenched with 10percent K2CO3 solution. The organic product was extracted with CH2Cl2 and the organic layer was washed with H2O and brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash column chromatography (silica 230-400 mesh, eluent 1-2percent MeOH in CH2Cl2) to afford methyl 2-cyanoisonicotinate (1.75 g, yield 33percent) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) delta 8.97 - 8.95 (d, J = 5.0 Hz, 1 H), 8.41 (m, 1 H), 8.15 - 8.13 (dd, J = 4.8 Hz, 1.6 Hz, 1 H), 3.92 (s, 3H).
	With triethylamine; In acetonitrile; at 150℃; under 6000.6 Torr;Flow reactor;	A solution of methyl 4-carboxypyridine (1M in MeCN) and a solution of mCPBA (1M in MeCN) were flowed via a T-mixer into a 10mL flow reactor at 95°C at a rate of 1.0mL per minute (Scheme 3). The solution of methyl 4-carboxypyridine N-oxide exiting the first reactor was combined with TMSCN/NEt3 (1:2.5, 1M in MeCN) via a second T-mixer. This solution was flowed into a 5mL reactor at 150°C at a rate of 0.2mL per minute. The solution exiting the reactor was collected and the solvent evaporated to provide methyl 2-cyanoisonicotinate (4).

Reference： [1]Patent: WO2013/127268,2013,A1 .Location in patent: Page/Page column 71; 72
[2]Patent: EP2533783,2015,B1 .Location in patent: Paragraph 0425-0426
[3]Tetrahedron,2018,vol. 74,p. 3165 - 3170

26
[ 26218-75-7 ]
[ 3783-38-8 ]
4-methoxycarbonyl-2-(6-methoxycarbonylpyridin-2-yl)pyridine N-oxide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With tri-tert-butylphosphonium tetrafluoroborate; palladium diacetate; potassium carbonate In toluene at 110℃; for 24h; Inert atmosphere;	10.4 4.10.4. 4-Methoxycarbonyl-2-(6-methoxycarbonylpyridin-2-yl)pyridine N-oxide Pd(OAc)2 (15.6 mg, 0.070 mmoles), [P(t-Bu)3H]BF4 (60.4 mg,0.21 mmoles), K2CO3 (384 mg, 2.8 mmoles), methyl 2-bromopicolinate(300 mg, 1.4 mmoles), and 4-methoxycarbonylpyridine Noxide(858 mg, 5.6 mmoles) were added to a dried flask. The flaskwas fitted with a reflux condenser capped with a septum, evacuated,and purged with N2(g) (5 times). Dry toluene (9.0 mL) wasadded via syringe, and the reaction mixture was stirred at 110 Cfor 24 h. The reaction mixture was cooled to room temperatureand filtered through Celite, and the filtrate was concentratedunder reduced pressure. The crude product was purified by chromatographyon silica (1% v/v MeOH in EtOAc) to afford the titlecompound (266 mg, 66%) as a pale yellow solid with mp 193.3-197.0 C. 1H NMR (400 MHz, CDCl3, d): 8.88 (d, J = 8.0 Hz, 1H),8.74 (d, J = 2.4 Hz, 1H), 8.31 (d, J = 6.8 Hz, 1H), 8.18, (d, J = 7.6 Hz,1H), 7.99 (t, J = 7.6 Hz, 1H), 7.87 (dd, J = 2.4, 6.8 Hz, 1H); 13C NMR(100 MHz, CDCl3, d): 165.3, 163.4, 150.2, 149.9, 149.4, 141.9,138.0, 128.9, 127.7, 125.7, 124.9, 124.1, 53.1, 52.8; HRMS (ESI)m/z 289.0818 [calc’d for C14H13N2O5 (M+H)+ 289.0819

Reference： [1]Vasta, James D.; Raines, Ronald T. [Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 13, p. 3081 - 3090]

27
[ 3783-38-8 ]
[ 577778-58-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: hydrazine hydrate / methanol / 2 h / 60 °C / Inert atmosphere 2.1: sodium methylate / methanol / 2 h / 40 °C / Inert atmosphere 2.2: 3 h 3.1: carbamic chloride / N,N-dimethyl-formamide / 1 h / 40 °C / Inert atmosphere 3.2: 1.5 h / 5 °C 4.1: phosphoric acid / water; iso-butanol / 8 h / 80 °C
	Multi-step reaction with 4 steps 1.1: hydrazine hydrate / methanol / 2 h / 60 °C / Inert atmosphere 2.1: sodium methylate / methanol / 2 h / 40 °C / Inert atmosphere 2.2: 3 h 3.1: N,N-Dimethylcarbamoyl chloride / N,N-dimethyl-formamide / 1 h / 40 °C 3.2: 1.5 h 4.1: phosphoric acid / water; butan-1-ol / 8 h / 80 °C
	Multi-step reaction with 4 steps 1.1: hydrazine hydrate / methanol / 2 h / 60 °C / Inert atmosphere 2.1: sodium methylate / methanol / 2 h / 40 °C / Inert atmosphere 2.2: 3 h 3.1: N,N-Dimethylcarbamoyl chloride / N,N-dimethyl-formamide / 1 h / 40 °C 3.2: 1.5 h 4.1: phosphoric acid / water; butan-1-ol / 8 h / 80 °C

	Multi-step reaction with 3 steps 1: N,N-Dimethylcarbamoyl chloride; copper(l) iodide / acetonitrile / 5 h / 80 °C 2: hydrazine hydrate / ethanol / 5 h / 80 °C 3: sodium methylate / methanol / 10 h / Reflux
	Multi-step reaction with 3 steps 1: N,N-Dimethylcarbamoyl chloride; copper(l) iodide / acetonitrile / 7 h / 90 °C 2: hydrazine hydrate / ethanol / 5 h / 80 °C 3: sodium methylate / methanol / 10 h / Reflux
	Multi-step reaction with 3 steps 1: N,N-Dimethylcarbamoyl chloride; copper(l) iodide / acetonitrile / 8 h / 90 °C 2: hydrazine hydrate / ethanol / 5 h / 80 °C 3: sodium methylate / methanol / 10 h / Reflux
	Multi-step reaction with 4 steps 1.1: hydrazine hydrate / methanol / 8 h / 50 °C / Large scale 2.1: sodium methylate / methanol / 1 h / 20 °C 2.2: 20 h / 90 °C 3.1: isopropyl alcohol / 2 h / Reflux 4.1: N,N-Dimethylcarbamoyl chloride / N,N-dimethyl-formamide / 1 h / 5 - 10 °C 4.2: 2 h / 50 °C

Reference： [1]Current Patent Assignee: CHINA NATIONAL PHARMACEUTICAL GROUP CORPORATION - CN105367490, 2016, A
[2]Current Patent Assignee: CHINA NATIONAL PHARMACEUTICAL GROUP CORPORATION - CN105348264, 2016, A
[3]Current Patent Assignee: CHINA NATIONAL PHARMACEUTICAL GROUP CORPORATION - CN105348264, 2016, A
[4]Current Patent Assignee: ZHUANG YAN - CN104151297, 2016, B
[5]Current Patent Assignee: ZHUANG YAN - CN104151297, 2016, B
[6]Current Patent Assignee: ZHUANG YAN - CN104151297, 2016, B
[7]Current Patent Assignee: BEIJING CHENGJI PHARMACEUTICAL - CN108250184, 2018, A

28
[ 557-21-1 ]
[ 3783-38-8 ]
[ 94413-64-6 ]

Yield	Reaction Conditions	Operation in experiment
65%	With N,N-Dimethylcarbamoyl chloride; In toluene; for 6h;Reflux; Inert atmosphere;	A reaction mixture of 4-(methoxycarbonyl)pyridine-1-oxide27 (0.20 g, 1.30 mmol), dimethylcarbamoyl chloride (DMCC, 0.12 mL, 1.30 mmol) and Zn(CN)2 (0.23 g, 1.96 mmol) in toluene (15 mL) was heated to reflux under an argon atmosphere for 6 h. The reaction mixture was cooled to room temperature and deionised H2O (10 mL) was added, and stirring was continued for 15 min. The organic layer was separated, washed with brine, dried over MgSO4 and concentrated under reduced pressure to yield an orange solid (0.21 g, 65percent) which required no further purification. m.p. 100-103 °C; numax (KBr) 2958, 2852, 2237, 1726, 1441, 1397, 1298, 1209, 1116, 974, 934, 882, 869, 765 cm-1; deltaH (300 MHz, CDCl3) 8.90 (1 H, dd, J 4.9, 0.8 Hz, pyr-H), 8.24 (1 H, dd, J 1.5, 0.8 Hz, pyr-H), 8.07 (1 H, dd, J 4.9, 1.5 Hz, pyr-H), 4.01 (3 H, s, OCH3); deltaC (75 MHz, CDCl3) 162.6 (C=O), 151.0, 137.7, 133.8, 126.6, 125.0, 115.5 (CN), 52.3 (OCH3); HRMS (ESI): [M+H]+, found 163.0509. C8H7N2O2 requires 163.0502. NMR data is in agreement with literature data.13

Reference： [1]Tetrahedron,2016,vol. 72,p. 8470 - 8478

29
[ 3783-38-8 ]
[ 135048-32-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N,N-Dimethylcarbamoyl chloride; copper(l) iodide / acetonitrile / 5 h / 80 °C 2: hydrazine hydrate / ethanol / 5 h / 80 °C
	Multi-step reaction with 2 steps 1: N,N-Dimethylcarbamoyl chloride; copper(l) iodide / acetonitrile / 7 h / 90 °C 2: hydrazine hydrate / ethanol / 5 h / 80 °C
	Multi-step reaction with 2 steps 1: N,N-Dimethylcarbamoyl chloride; copper(l) iodide / acetonitrile / 8 h / 90 °C 2: hydrazine hydrate / ethanol / 5 h / 80 °C

Reference： [1]Current Patent Assignee: ZHUANG YAN - CN104151297, 2016, B
[2]Current Patent Assignee: ZHUANG YAN - CN104151297, 2016, B
[3]Current Patent Assignee: ZHUANG YAN - CN104151297, 2016, B

30
[ 3783-38-8 ]
[ 748101-41-9 ]
[ 94413-64-6 ]

Yield	Reaction Conditions	Operation in experiment
94%	With copper(l) iodide; N,N-Dimethylcarbamoyl chloride; In acetonitrile; at 80℃; for 5h;	The formula (5) compound methyl isobutyl niacin-N-oxide 1.53g (10mmol), b a carbamic chloride (0.11 ml, 11mmol), zinc cyanide (1.40g, 12mmol), cuprous iodide 0.19g (1mmol) dissolved in 50 ml of acetonitrile, mixtures in 80 °C reaction under 5 hours, TLC detection reaction (hexane/ethyl acetate = 1 the [...] 1), after the reaction, cooling to room temperature, add 20 ml water to stir reaction 5-30 minutes, removed the organic layer, the aqueous layer extracted with ethyl acetate three times, each 50 ml, combined with the organic layer, anhydrous sodium sulfate for drying, distilling solvent under reduced pressure, to obtain crude products, crude product using normal hexane/ethyl acetate = 4 the [...] 1 column chromatography, to obtain strawcoloured solid 1.53g, yield 94percent, HPLC purity ( unitary method ): 97.7percent ; melting point: 107.5-108.7 °C.

Reference： [1]Patent: CN104151297,2016,B .Location in patent: Paragraph 0037; 0038

31
potassium cyanide [ No CAS ]
[ 3783-38-8 ]
[ 94413-64-6 ]

Yield	Reaction Conditions	Operation in experiment
70.8%	With copper(l) iodide; N,N-Dimethylcarbamoyl chloride; In acetonitrile; at 90℃; for 8h;	The compound of formula (5), methyl isonicotinic acid-N-oxide, 1. 53 g (10 mmol), dimethylcarbamoyl chloride (0.1 mmol, 11 mmol), potassium cyanide (1.3 g, 20 mmol) and cuprous iodide 0.19 g (1 mmol) were dissolved in 50 ml of acetonitrile and mixed The reaction was carried out at 90 ° C for 8 hours. The reaction was monitored by TLC (n-hexane / ethyl acetate = 1: 1). After completion of the reaction, The reaction was stirred for 5 - 30 minutes at room temperature, the organic layer was discarded and the aqueous layer was extracted three times with 50 mL each of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure to give the crude product which was recrystallized from n-hexane / ethyl acetate = 4: 1 Column chromatography to give 1.15 g of a light yellow solid, yield 70.8

Reference： [1]Patent: CN104151297,2016,B .Location in patent: Paragraph 0041; 0042

32
[ 3783-38-8 ]
[ 77-78-1 ]
N-methoxy-4-(methoxycarbonyl)pyridinium methylsulfate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	In neat (no solvent) at 0 - 60℃; for 4h; Inert atmosphere;

Reference： [1]Ma, Xiaoshen; Dang, Hester; Rose, John A.; Rablen, Paul; Herzon, Seth B. [Journal of the American Chemical Society, 2017, vol. 139, # 16, p. 5998 - 6007]

33
[ 3783-38-8 ]
[ 1467-79-4 ]
methyl 2-(3,3-dimethylureido)isonicotinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With methanesulfonic acid at 60℃; for 2h; Green chemistry; regioselective reaction;

Reference： [1]Rassadin, Valentin A.; Zimin, Dmitry P.; Raskil'dina, Gulnara Z.; Ivanov, Alexander Yu.; Boyarskiy, Vadim P.; Zlotskii, Semen S.; Kukushkin, Vadim Yu. [Green Chemistry, 2016, vol. 18, # 24, p. 6630 - 6636]

34
[ 3783-38-8 ]
potassium (trifluoromethyl)trifluoroborate [ No CAS ]
C₈H₇BF₅NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With boron trifluoride diethyl etherate In dichloromethane at 20℃; for 16h; Inert atmosphere; Cooling with ice;

Reference： [1]Smirnov, Vladimir O.; Maslov, Anton S.; Kokorekin, Vladimir A.; Korlyukov, Alexander A.; Dilman, Alexander D. [Chemical Communications, 2018, vol. 54, # 18, p. 2236 - 2239]

35
[ 3783-38-8 ]
[ 103-54-8 ]
[ 75961-62-5 ]

Yield	Reaction Conditions	Operation in experiment
40%	With tetrafluoroboric acid; 10-phenyl-9-(2,4,6-trimethylphenyl)acridinium tetrafluoroborate In dichloromethane; water at 20℃; for 48h; Inert atmosphere; Sealed tube; Irradiation;

Reference： [1]Zhou, Wang; Miura, Tomoya; Murakami, Masahiro [Angewandte Chemie - International Edition, 2018, vol. 57, # 18, p. 5139 - 5142][Angew. Chem., 2018, vol. 130, # 18, p. 5233 - 5236,4]

36
[ 887144-97-0 ]
[ 3783-38-8 ]
[ 82113-66-4 ]
4-(methoxycarbonyl)-N-(trifluoromethoxy)pyridinium triflimide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	Stage #1: methyl isonicotinate N-oxide; trimethylsilyl bis(trifluoromethanesulfonyl)imide In dichloromethane at 20℃; Schlenk technique; Inert atmosphere; Glovebox; Stage #2: Togni's reagent In dichloromethane at 20℃; for 12h; Schlenk technique; Inert atmosphere; Glovebox;

Reference： [1]Jelier, Benson J.; Tripet, Pascal F.; Pietrasiak, Ewa; Franzoni, Ivan; Jeschke, Gunnar; Togni, Antonio [Angewandte Chemie - International Edition, 2018, vol. 57, # 42, p. 13784 - 13789][Angew. Chem., 2018, vol. 130, p. 13980 - 13985,6]

37
[ 3783-38-8 ]
[ 4450-76-4 ]
4-(methoxycarbonyl)-1-(pentyloxy)pyridin-1-ium 4-methylbenzenesulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	In acetonitrile at 60 - 70℃;

Reference： [1]Kim, Inwon; Park, Bohyun; Kang, Gyumin; Kim, Jiyun; Jung, Hoimin; Lee, Hyeonyeong; Baik, Mu-Hyun; Hong, Sungwoo [Angewandte Chemie - International Edition, 2018, vol. 57, # 47, p. 15517 - 15522][Angew. Chem., 2018, vol. 130, # 47, p. 15743 - 15748,6]

38
[ 3783-38-8 ]
[ 17178-11-9 ]
1-(2-ethoxyethoxy)-4-(methoxycarbonyl)pyridin-1-ium 4-methylbenzenesulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	In acetonitrile at 60 - 70℃;

39
[ 3783-38-8 ]
[ 21336-37-8 ]
1-(2-cyclohexylethoxy)-4-(methoxycarbonyl)pyridin-1-ium 4-methylbenzenesulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	In acetonitrile at 60 - 70℃;

40
[ 3783-38-8 ]
[ 26831-48-1 ]
1-(2-((3r,5r,7r)-adamantan-1-yl)ethoxy)-4-(methoxycarbonyl)pyridin-1-ium 4-methylbenzenesulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	In acetonitrile at 60 - 70℃;

41
[ 3783-38-8 ]
C₂₀H₂₆N₄O₅S [ No CAS ]
(1-((6-(3,7-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)hexan-2-yl)oxy)-4-(methoxycarbonyl)pyridin-1-ium) (4-methylbenzenesulfonate) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	In acetonitrile at 60 - 70℃;

42
[ 888329-88-2 ]
[ 3783-38-8 ]
methyl 2-[2-oxo-2-(2-oxooxazolidin-3-yl)-1-phenylethyl]isonicotinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With 9-(2-mesityl)-10-methylacridinium perchlorate In acetonitrile at 20℃; for 16h; Irradiation;

Reference： [1]Markham, Jonathan P.; Wang, Ban; Stevens, Edwin D.; Burris, Stuart C.; Deng, Yongming [Chemistry - A European Journal, 2019, vol. 25, # 26, p. 6638 - 6644]

43
[ 3783-38-8 ]
[ 501-65-5 ]
methyl 2-(2-oxo-1,2-diphenylethyl)isonicotinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With 9-(2-mesityl)-10-methylacridinium perchlorate In acetonitrile at 20℃; for 24h; Irradiation;

Reference： [1]Markham, Jonathan P.; Wang, Ban; Stevens, Edwin D.; Burris, Stuart C.; Deng, Yongming [Chemistry - A European Journal, 2019, vol. 25, # 26, p. 6638 - 6644]

44
[ 3783-38-8 ]
C₂₃H₃₃IO₄ [ No CAS ]
2-cyclohexyl-4-(methoxycarbonyl)pyridine 1-oxide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
18%	With bathophenanthroline; copper(l) chloride In dichloromethane at 20℃; for 12h; Irradiation;

Reference： [1]Liu, Duan-Yang; Liu, Xu; Gao, Yan; Wang, Chao-Qun; Tian, Jie-Sheng; Loh, Teck-Peng [Organic Letters, 2020, vol. 22, # 22, p. 8978 - 8983]

45
[ 1530-87-6 ]
[ 3783-38-8 ]
methyl 2-(piperidine-1-carboxamido)isonicotinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With methanesulfonic acid at 60℃; for 3h;

Reference： [1]Baykov, Sergey V.; Boyarskaya, Irina A.; Boyarskiy, Vadim P.; Geyl, Kirill K.; Kasatkina, Svetlana O. [Organic and Biomolecular Chemistry, 2021, vol. 19, # 27, p. 6059 - 6065]

46
[ 3783-38-8 ]
[ 2089-33-0 ]
C₁₆H₁₆N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With N-ethyl-N,N-diisopropylamine; bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate In tetrahydrofuran at 25℃; for 12h;

Reference： [1]Yuan, Changping; Han, Fuzhong; Jia, Lina; Hu, Xiangping [Tetrahedron Letters, 2021, vol. 78]

47
[ 100-64-1 ]
[ 3783-38-8 ]
C₁₃H₁₆N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With N-ethyl-N,N-diisopropylamine; bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate In tetrahydrofuran at 25℃; for 12h;

Reference： [1]Yuan, Changping; Han, Fuzhong; Jia, Lina; Hu, Xiangping [Tetrahedron Letters, 2021, vol. 78]

48
[ 3783-38-8 ]
[ 28150-91-6 ]
C₂₂H₁₇N₃O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With potassium phosphate; bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate In tetrahydrofuran at 25℃; for 12h;

Reference： [1]Yuan, Changping; Han, Fuzhong; Jia, Lina; Hu, Xiangping [Tetrahedron Letters, 2021, vol. 78]

49
[ 3783-38-8 ]
[ 98820-73-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: palladium diacetate; potassium carbonate; tri tert-butylphosphoniumtetrafluoroborate / toluene / 20 - 120 °C 2: palladium on activated charcoal; hydrogen / ethanol / 4 h / 20 °C

Reference： [1]Gu, Yifan; Lewis, Jared C.; Liu, Bingqing; Sahoo, Dipankar; Zubi, Yasmine S. [Chemical Science, 2022, vol. 13, # 5, p. 1459 - 1468]

50
[ 3783-38-8 ]
[ 220340-37-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: palladium diacetate; potassium carbonate; tri tert-butylphosphoniumtetrafluoroborate / toluene / 20 - 120 °C 2: palladium on activated charcoal; hydrogen / ethanol / 4 h / 20 °C 3: lithium borohydride / tetrahydrofuran / 13 h / 0 - 20 °C

Reference： [1]Gu, Yifan; Lewis, Jared C.; Liu, Bingqing; Sahoo, Dipankar; Zubi, Yasmine S. [Chemical Science, 2022, vol. 13, # 5, p. 1459 - 1468]

51
[ 3783-38-8 ]
C₃₁H₂₆N₆ORu⁽²⁺⁾ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: palladium diacetate; potassium carbonate; tri tert-butylphosphoniumtetrafluoroborate / toluene / 20 - 120 °C 2: palladium on activated charcoal; hydrogen / ethanol / 4 h / 20 °C 3: lithium borohydride / tetrahydrofuran / 13 h / 0 - 20 °C 4: ammonium hexafluorophosphate / ethanol; water / Reflux

Reference： [1]Gu, Yifan; Lewis, Jared C.; Liu, Bingqing; Sahoo, Dipankar; Zubi, Yasmine S. [Chemical Science, 2022, vol. 13, # 5, p. 1459 - 1468]

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Code	Phrase
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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. 3783-38-8 ]

Quality Control of [ 3783-38-8 ]

Related Doc. of [ 3783-38-8 ]

Product Details of [ 3783-38-8 ]

Safety of [ 3783-38-8 ]

Application In Synthesis of [ 3783-38-8 ]

[ 3783-38-8 ] Synthesis Path-Upstream 1~12

[ 3783-38-8 ] Synthesis Path-Downstream 1~51

Related Functional Groups of [ 3783-38-8 ]

Esters

Related Parent Nucleus of [ 3783-38-8 ]

Pyridines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 3783-38-8 ]

Related Parent Nucleus of
[ 3783-38-8 ]