Name: 13121-99-8|4-Pyridylacetonitrile|98%
Brand: Ambeed
SKU: A292957
Price: 7.0 USD
Availability: InStock
Rating: 99 (29 reviews)

1
[ 13121-99-8 ]
[ 5451-38-7 ]

Yield	Reaction Conditions	Operation in experiment
76%	With hydrogen sulfide; ammonia In methanol at 0 - 25℃; for 16.5h;	3.1 2-(Pyridin-4-ylmethyl)-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine hydrochloride (AMN-02)Stage 1 : 2-(Pyridin-4-yl)ethanethioamideHydrogen sulfide was passed through a solution of 2-(pyridin-4-yl)acetonitrile (2.5 g) in 30 % strength ammoniacal methanol (12 ml) at 0 0C for 30 minutes. The reaction mixture obtained was stirred at 25 0C for 16 hours. The solid which had precipitated out was filtered off, washed with ether and dried. The desired product was obtained in a yield of 76 %.
	With ammonia Einleiten von Schwefelwasserstoff;

Reference： [1]Current Patent Assignee: Gruenenthal Pharma GmbH & Co. Kommanditgesellschaft - WO2009/124746, 2009, A1 Location in patent: Page/Page column 196
[2]Gardner et al. [Journal of Organic Chemistry, 1954, vol. 19, p. 753,755]

2
[ 1120-87-2 ]
[ 75-05-8 ]
[ 13121-99-8 ]

Yield	Reaction Conditions	Operation in experiment
48%	Stage #1: acetonitrile With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.75h; Stage #2: 4-bromopyridin In tetrahydrofuran; hexane at -78 - 20℃; for 2.5h;
60 % Chromat.	With potassium amide In diethyl ether at -70℃; for 0.666667h; Irradiation;

Reference： [1]Skerlj; Bogucki; Bridger [Synlett, 2000, # 10, p. 1488 - 1490]
[2]Yakubov, A. P.; Belen'kii, L. I.; Gol'dfarb, Ya. L. [Bulletin of the Academy of Sciences of the USSR Division of Chemical Science, 1981, vol. 30, # 12, p. 2344 - 2347][Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1981, # 12, p. 2812 - 2815]

3
[ 13121-99-8 ]
[ 4637-24-5 ]
[ 103851-89-4 ]

Yield	Reaction Conditions	Operation in experiment
95%	In N,N-dimethyl-formamide at 110℃; for 5h;	8.2 (2) Synthesis of 3-dimethylamino-2-pyridineacrylonitrile (4) Add 3 0.5 g (4.0 mmol) and 5 mL of DMF to the dried eggplant-shaped bottle,Stir until dissolved;8 mL of N, N-dimethylformamide dimethyl acetal was added, and the mixture was heated to 110 ° C for 5 hours (TLC monitoring).After cooling to room temperature, 30 mL of water was added, and the mixture was extracted with ethyl acetate (3 × 10 mL). The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate.Filtration and the filtrate removed the organic phase under reduced pressure.The obtained oil was purified by silica gel column chromatography (eluent: A = 40: 1) to obtain 4 0.70 g of a brown solid with a yield of 95%;
	With methanol 2.) RT, 1 h; Yield given. Multistep reaction;
	In toluene at 100℃; for 2h;	10.1 To a solution of 2-(4-pyridyl)acetonitrile (2 g) in toluene (20 mL) was added N,N-dimethylformamide dimethyl acetal (6.72 g) and the mixture was heated at 100°C for 2 hours. The reaction mixture was concentrated to give 3-(dimethylamino)-2-(4-pyridyl)prop-2-enenitrile, which was used without further purification. NMR (400 MHz, DMSO-de) 8.34 (d, 2H), 7.81 (s, 1 H), 7.27 (d, 2H), 3.22 - 3.31 (m, 6H)

Reference： [1]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES - CN110496127, 2019, A Location in patent: Paragraph 0191; 0198-0199
[2]Lipinski; LaMattina; Oates [Journal of Medicinal Chemistry, 1986, vol. 29, # 11, p. 2154 - 2163]
[3]Current Patent Assignee: Syngenta (in: Sinochem Holdings); SINOCHEM HOLDINGS CORPORATION LTD - WO2021/64073, 2021, A1 Location in patent: Page/Page column 86-87

4
[ 13121-99-8 ]
[ 78-84-2 ]
(E)-4-Methyl-2-pyridin-4-yl-pent-2-enenitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	With piperidine; acetic acid In benzene for 4h; Heating;

Reference： [1]Bernhart; Condamine; Demarne; Roncucci; Gagnol; Gautier; Serre [Journal of Medicinal Chemistry, 1983, vol. 26, # 3, p. 451 - 455]

5
[ 10429-82-0 ]
[ 13121-99-8 ]
[ 751462-82-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,1997,vol. 7,p. 2531 - 2536

6
[ 13121-99-8 ]
[ 107-13-1 ]
[ 263272-74-8 ]

Yield	Reaction Conditions	Operation in experiment
60%	With tetraethylammonium hydroxide In ethanol at 20℃; for 4h;

Reference： [1]Fadda; Refat, Hala M. [Synthetic Communications, 2000, vol. 30, # 2, p. 341 - 350]

7
[ 54730-30-2 ]
[ 13121-99-8 ]
3-(2,2-dimethyl-2<i>H</i>-chromen-6-yl)-2-pyridin-4-yl-acrylonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-hydroxy-3-C-prenylbenzaldehyde With polystyrene-based selenenyl bromide resin In dichloromethane at 0 - 25℃; for 0.333333h; Stage #2: pyridin-4-ylacetonitrile With potassium ethoxide In tetrahydrofuran; ethanol at 25℃; for 3h; Stage #3: With dihydrogen peroxide In tetrahydrofuran at 25℃; for 0.333333h; Further stages.;

Reference： [1]Nicolaou; Pfefferkorn; Roecker; Cao; Barluenga; Mitchell [Journal of the American Chemical Society, 2000, vol. 122, # 41, p. 9939 - 9953]

8
[ 18423-13-7 ]
[ 13121-99-8 ]
3-(8-methoxy-2,2-dimethyl-2<i>H</i>-chromen-6-yl)-2-pyridin-4-yl-acrylonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-hydroxy-3-methoxy-5-(3-methylbut-2-en-1-yl)benzaldehyde With polystyrene-based selenenyl bromide resin In dichloromethane at 0 - 25℃; for 0.333333h; Stage #2: pyridin-4-ylacetonitrile With potassium ethoxide In tetrahydrofuran; ethanol at 25℃; for 3h; Stage #3: With dihydrogen peroxide In tetrahydrofuran at 25℃; for 0.333333h; Further stages.;

Reference： [1]Nicolaou; Pfefferkorn; Roecker; Cao; Barluenga; Mitchell [Journal of the American Chemical Society, 2000, vol. 122, # 41, p. 9939 - 9953]

9
[ 1448-87-9 ]
[ 13121-99-8 ]
[ 59563-77-8 ]

Yield	Reaction Conditions	Operation in experiment
48%	Stage #1: 2-chloroquinoxaline; pyridin-4-ylacetonitrile With sodium hexamethyldisilazane In tetrahydrofuran at 20℃; for 10h; Stage #2: With sodium peroxide; ammonium acetate In tetrahydrofuran at 20℃; for 10h;

Reference： [1]Yin, Zhiwei; Zhang, Zhongxing; Kadow, John F.; Meanwell, Nicholas A.; Wang, Tao [Journal of Organic Chemistry, 2004, vol. 69, # 4, p. 1364 - 1367]

10
[ 459-57-4 ]
[ 13121-99-8 ]
(E)-3-(4-fluorophenyl)-2-(pyridin-4-yl)acrylonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	In N,N-dimethyl-formamide at 120℃; for 24h;
40.2%	With potassium carbonate In methanol at 80℃; for 4h;
40.2%	With potassium carbonate In methanol at 80℃; for 4h;

Reference： [1]Location in patent: experimental part Percino, M. Judith; Chapela, Victor M.; Perez-Gutierrez, Enrique; Ceron, Margarita; Soriano, Guillermo [Chemical Papers, 2011, vol. 65, # 1, p. 42 - 51]
[2]Current Patent Assignee: GRITSCIENCE BIOPHARMACEUTICALS - WO2021/190615, 2021, A1 Location in patent: Paragraph 00402-00405
[3]Current Patent Assignee: GRITSCIENCE BIOPHARMACEUTICALS - WO2021/190616, 2021, A1 Location in patent: Paragraph 00265-00268
[4]Bullington, James; Argentieri, Dennis; Averill, Kristin; Carter, Demetrius; Cavender, Druie; Fahmy, Bohumila; Fan, Xiaodong; Hall, Daniel; Heintzelman, Geoffrey; Jackson, Paul; Leung, Wai-Ping; Li, Xun; Ling, Ping; Olini, Gilbert; Razler, Thomas; Reuman, Michael; Rupert, Kenneth; Russell, Ronald; Siekierka, John; Wadsworth, Scott; Wolff, Russell; Xiang, Bangping; Zhang, Yue-Mei [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 23, p. 6102 - 6106]

11
[ 13121-99-8 ]
[ 175532-12-4 ]

Yield	Reaction Conditions	Operation in experiment
	With hydroxylamine hydrochloride; triethylamine In methanol at 20℃;

Reference： [1]Fish, Paul V.; Allan, Gillian A.; Bailey, Simon; Blagg, Julian; Butt, Richard; Collis, Michael G.; Greiling, Doris; James, Kim; Kendall, Jackie; McElroy, Andrew; McCleverty, Dawn; Reed, Charlotte; Webster, Robert; Whitlock, Gavin A. [Journal of Medicinal Chemistry, 2007, vol. 50, # 15, p. 3442 - 3456]

12
[ 13121-99-8 ]
[ 292638-85-8 ]
C₁₄H₁₄N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With potassium <i>tert</i>-butylate In tetrahydrofuran at 25℃; for 0.5h;

Reference： [1]DeGraffenreid, Michael R.; Bennett, Sarah; Caille, Sebastien; De Turiso, Felix Gonzalez-Lopez; Hungate, Randall W.; Julian, Lisa D.; Kaizerman, Jacob A.; McMinn, Dustin L.; Rew, Yosup; Sun, Daqing; Yan, Xuelei; Powers, Jay P. [Journal of Organic Chemistry, 2007, vol. 72, # 19, p. 7455 - 7458]

13
[ 13121-99-8 ]
[ 92788-10-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 2: acetic acid, H₂SO₄, HCl / 3.5 h / Heating
	Multi-step reaction with 3 steps 1: 61 percent / RhCl₃*3H₂O, Ph₃P, anh. NaHCO₃ / 20 h / Heating 2: Triton B / 2-methyl-propan-2-ol / 3 h 3: 4.17 g / conc. H₂SO₄ / acetic acid / 3 h / Heating

Reference： [1]Foster, Allan B.; Jarman, Michael; Leung, Chui-Sheung; Rowlands, Martin G.; Taylor, Grahame N.; et al. [Journal of Medicinal Chemistry, 1985, vol. 28, # 2, p. 200 - 204]
[2]Leung; Rowlands; Jarman; Foster; Griggs; Wilman [Journal of Medicinal Chemistry, 1987, vol. 30, # 9, p. 1550 - 1554]

14
[ 13121-99-8 ]
[ 5344-27-4 ]

Reference： [1]Helvetica Chimica Acta,1982,vol. 65,p. 1868 - 1884

15
[ 13121-99-8 ]
[ 72434-26-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 98 percent / acetic acid, piperidine / benzene / 4 h / Heating 2: H₂ / 5 percent Pd/C / ethanol / 760 Torr / Ambient temperature

Reference： [1]Bernhart; Condamine; Demarne; Roncucci; Gagnol; Gautier; Serre [Journal of Medicinal Chemistry, 1983, vol. 26, # 3, p. 451 - 455]

16
[ 13121-99-8 ]
[ 83918-25-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 98 percent / acetic acid, piperidine / benzene / 4 h / Heating 2: H₂ / 5 percent Pd/C / ethanol / 760 Torr / Ambient temperature 3: sodamide / toluene / 2 h / Heating

Reference： [1]Bernhart; Condamine; Demarne; Roncucci; Gagnol; Gautier; Serre [Journal of Medicinal Chemistry, 1983, vol. 26, # 3, p. 451 - 455]

17
[ 13121-99-8 ]
[ 78833-26-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 98 percent / acetic acid, piperidine / benzene / 4 h / Heating 2: H₂ / 5 percent Pd/C / ethanol / 760 Torr / Ambient temperature 3: sodamide / toluene / 2 h / Heating 4: 16 percent / conc. H₂SO₄ / 1 h / 120 °C

Reference： [1]Bernhart; Condamine; Demarne; Roncucci; Gagnol; Gautier; Serre [Journal of Medicinal Chemistry, 1983, vol. 26, # 3, p. 451 - 455]

18
[ 13121-99-8 ]
[ 107-04-0 ]
[ 680973-08-4 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: pyridin-4-ylacetonitrile; 1-Bromo-2-chloroethane With sodium hydroxide; benzyltriethylammonium bromide In water at 20 - 50℃; for 4.25h; Stage #2: With ammonia; hydrogen In methanol; water	3 Example 3; Preparation of [(2-AMINO-1-CYCLOPROPPYRIDIN-4-YLLETHYL] A mixture [OF PYRIDIN-4-YL-ACETONITRILE] (1.2 g, 7.76 mmol), benzyl- triethylammonium bromide (63 mg, 0.23 mmol), and 1-bromo-2-chloro-ethane (16.7 g, 116.4 mmol) at [50°C] was treated with the dropwise addition of 50% aqueous sodium hydroxide over 15 minutes. Stirring continued at [50°C] for 2h then at room temperature for an additional 2h. The reaction mixture was diluted with water and extracted several times with dichloromethane. The organic layers were combined, washed with water then separated, dried (Na2SO4) and concentrated to give 1.2 g of pure product as a red brown solid. The solid was dissolved in 20 mL [OF 2N] ammonium in methanol and treated with a catalytic amount of Raney-Nickel in water. The resulting mixture was shaken overnight under 50 psi of hydrogen. The mixture was filtered and concentrated to give 740 mg of a light tan oil. [[00255]] MS (ES) m/e 149.2 [M+H] +

Reference： [1]Current Patent Assignee: PERRIGO COMPANY PUBLIC LIMITED COMPANY - WO2004/33436, 2004, A1 Location in patent: Page 69

19
[ 50-01-1 ]
[ 13121-99-8 ]
[ 456-48-4 ]
[ 518354-96-6 ]

Yield	Reaction Conditions	Operation in experiment
	With ethanol; sodium for 48h; Heating / reflux;	1 Example 1: 2-Amino-6-(3-fluorophenyl)-5-(4-pyridyl)-3,4-dihydro-4-pyrimidinone; (Method 1) Sodium (3.2 g, 139 mmol) was dissolved in ethanol (200 mL), and then 4-pyridylacetonitrile (10.0 g, 64.7 mmol), 3-fluorobenzaldehyde (7.3 mL, 68.8 mmol) and guanidine hydrochloride (7.0 g, 73.3 mmol) were successively added thereto under ice-cooling, followed by heating under reflux for two days. The insoluble matters were filtered off, and the filtrate was concentrated. The residue was subjected to silica gel column chromatography (eluent; dichloromethane, dichloromethane:methanol=20:1, 10:1, 5:1), to give the 5,6-dihydro form of the title compound (13.6 g) as a crude product. To the crude product was added sulfur (26.4 g, 82.3 mmol in terms of sulfur), followed by heating at 185°C for 2.5 hours. After standing to cool, the reaction mixture was suspended in methanol. The insoluble matters were filtered off and washed with 2N hydrochloric acid. After concentrating methanol from the filtrate, the residue was washed with ethyl acetate twice. The aqueous layer was adjusted to pH 11 with a 5N aqueous sodium hydroxide solution, and washed with ethyl acetate twice. The aqueous layer was neutralized with 2N hydrochloric acid, and the resulting crystals were collected by filtration, and washed with water and ethyl acetate, to give the title compound (6.2 g, 34%) as a colorless solid. In this process, the title compound could also be obtained by isolating (E)-3-(3-fluorophenyl)-2-(4-pyridyl)-2-propenenitrile and then subjecting it to cyclization reaction with guanidine in a manner similar to that described for Referential Example 3.

Reference： [1]Current Patent Assignee: EISAI CO LTD - EP1439176, 2004, A1 Location in patent: Page 22

20
[ 13121-99-8 ]
[ 456-48-4 ]
[ 518354-96-6 ]

Yield	Reaction Conditions	Operation in experiment
	With guanidine hydrochloride; sodium In ethanol for 48h; Heating / reflux;	12.1 (Method 1) Sodium (3.2 g, 139 mmol) was dissolved in ethanol (200 ml), and then 4-pyridylacetonitrile (10.0 g, 64.7 mmol), 3-fluorobenzaldehyde (7.3 ml, 68.8 mmol) and guanidine hydrochloride (7.0g, 73.3mmol) were successively added thereto, followed by heating under reflux for 2 days. The insoluble matters were filtered off and the filtrate was concentrated. The residue was subjected to silica gel column chromatography (elution solvent; dichloromethane, dichloromethane:methanol= 20:1, 10:1, 5:1), to give a 5,6-dihydro product (13.6 g) of the title compound as a crude product. Sulfur (26.4 g, 82.3 mmol as S) was added to the product, followed by heating at 185°C for 2.5 hours. After cooling as it was, the reaction mixture was suspended in methanol, and the insoluble matters were filtered off and washed with 2N hydrochloride. Methanol in the filtrate was concentrated and the residue was washed with ethyl acetate twice. The aqueous layer was adjusted to pH 11 with a 5N aqueous sodium hydroxide solution, washed with ethyl acetate twice and then neutralized with 2N hydrochloride. The resulting crystals were collected by filtration, and washed with water and ethyl acetate, to give the title compound (6.2 g, 34%) as a colorless solid. Furthermore, in this method, the title compound was also obtained by isolating (E)-3-(3-fluorophenyl)-2-(4-pyridyl)-2-propenenitrile and then subjecting it to a cyclization reaction with guanidine in a similar manner to Reference Example 4.

Reference： [1]Current Patent Assignee: EISAI CO LTD - EP1439175, 2004, A1 Location in patent: Page 44-45

21
[ 185400-06-0 ]
[ 13121-99-8 ]
4-(2,2-Dicyanoethenyl)-7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran [ No CAS ]
(E)-4-[2-Cyano-2-(pyridin-4-yl)ethenyl]-7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
46%	With sodium acetate In acetic acid	86 (E)-4-[2-Cyano-2-(4-pyridyl)ethenyl]-7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran (Compound 86) EXAMPLE 86 (E)-4-[2-Cyano-2-(4-pyridyl)ethenyl]-7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran (Compound 86) Compound IIa (2.3 g) obtained in Reference Example 1 was suspended in glacial acetic acid, and sodium acetate (2.3 g) and 4-pyridylacetonitrile (1.6 ml) were successively added thereto, followed by stirring at 110° C. for one hour. The reaction solution was poured into water and the mixture was extracted with ethyl acetate. The collected organic layer was washed with a saturated saline and dried over anhydrous magnesium sulfate. The residue was purified by silica gel column chromatography (ethyl acetate/toluene=1/9) and recrystallized from ethanol to give Compound 88 (1.6 g, 46%) as pale-yellow crystals. Melting point: 150-163° C. NMR(DMSO-d6, δ, ppm): 1.44(s, 6H), 3.33(s, 2H), 3.84 (s, 3H), 7.04(d, J=8.57 Hz, 1H), 7.71(d, J=5.94 Hz, 1H), 7.73(d, J=8.25 Hz, 1H), 7.98(s, 1H), 8.67(d, J=6.27 Hz, 1H) MASS(m/e): 306(M+) IR(KBr, cm-1): 2206, 1578, 1508
46%	With sodium acetate In acetic acid	86 (E)-4-[2-Cyano-2-(4-pyridyl)ethenyl]-7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran (Compound 86) EXAMPLE 86 (E)-4-[2-Cyano-2-(4-pyridyl)ethenyl]-7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran (Compound 86) Compound IIa (2.3 g) obtained in Reference Example 1 was suspended in glacial acetic acid, and sodium acetate (2.3 g) and 4-pyridylacetonitrile (1.6 ml) were successively added thereto, followed by stirring at 110° C. for one hour. The reaction solution was poured into water and the mixture was extracted with ethyl acetate. The collected organic layer was washed with a saturated saline and dried over anhydrous magnesium sulfate. The residue was purified by silica gel column chromatography (ethyl acetate/toluene=1/9) and recrystallized from ethanol to give Compound 88 (1.6 g, 46%) as pale-yellow crystals. Melting point: 150-163° C. NMR(DMSO-d6, δ, ppm): 1.44(s, 6H), 3.33(s, 2H), 3.84 (s, 3H), 7.04(d, J=8.57 Hz, 1H), 7.71(d, J=5.94 Hz, 1H), 7.73(d, J=8.25 Hz, 1H), 7.98(s, 1H), 8.67(d, J=6.27 Hz, 1H) MASS(m/e): 306(M+) IR(KBr, cm-1): 2206, 1578, 1508 Elemental analysis: C19H18N2O2 Found (%) C,74.63; H,5.95; N,9.25; Calcd.(%) C,74.49; H,5.92; N,9.14.

Reference： [1]Current Patent Assignee: Kyowa Kirin (in: Kirin Holdings); KIRIN HOLDINGS CO., LTD. - US2002/128290, 2002, A1
[2]Current Patent Assignee: Kyowa Kirin (in: Kirin Holdings); KIRIN HOLDINGS CO., LTD. - US6514996, 2003, B2

22
[ 66134-67-6 ]
[ 13121-99-8 ]
[ 148671-42-5 ]

Yield	Reaction Conditions	Operation in experiment
84%	With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 24h;	7 3-(4-Fluorophenyl)-3-oxo-2-(4-pyridyl)propionitrile (11) To a solution of 4-pyridylacetonitrile (9) (9.6 g, 81.3 mmol) and2,5-dioxopyrrolidinyl 4-fluorobenzoate (10) (19.3 g, 81.4 mmol) indimethylformamide (200 mL) was added potassium carbonate(11.2 g, 81.0 mmol), then stirred at room temperature for 24 h. The reaction solution was filtered off by Celite and the filtratewas evaporated in vacuo. The residue was added water and neutralizedwith aqueous solution of HCl. The formed precipitatewas collected by filtration and washed with water, followed bydiethyl ether and dried in a circulation dryer to afford the titlecompound 11 (16.3 g, 84%). Mp: 220.0-223.0 C; 1H NMR (CD3OD)d: 8.23-7.97 (m, 4H), 7.80-7.61 (m, 2H), 7.12 (t, J = 8.9 Hz, 2H); IR(KBr) 2180, 1636, 1608, 1542, 1492, 1408, 1374, 1342, 1222, 1202,1156, 830 cm1; MS (EI): m/z 240 (M+).
103%	With hydrogenchloride; potassium carbonate In <i>N</i>-methyl-acetamide; water	34.a (a) (a) Synthesis of 3-(4-fluorophenyl)-3-oxo-2-(4-pyridyl)propionitrile 32 g of 4-pyridylacetonitrile and 86 g of 2,5-dioxo-pyrrolidinyl 4-fluorobenzoate were dissolved in 1.3 L of dimethylformamide. After the addition of 164 g of potassium carbonate, the resulting mixture was stirred at room temperature for a day. After the reaction mixture was filtered through cerite, the filtrate was concentrated under reduced pressure. After water was added to the residue, this solution was neutralized with an aqueous solution of hydrochloric acid. The precipitated crystals were collected by filtration, washed with diethyl ether, and then dried in a stream of air to obtain 67 g (103% yield) of the title compound. Melting point: 220.0-223.0° C. (decomp.) 1H-NMR (CD3OD) δ: 8.23-7.97 (m, 4H), 7.80-7.61 (m, 2H), 7.12 (t, J=8.9 Hz, 2H) IR (KBr) ν max: 2180, 1636, 1608, 1542, 1492, 1408, 1374, 1342, 1222, 1202, 1156, 830 cm--1 Mass, m/e: 240 (M+), 123 (base)

Reference： [1]Hasumi, Koichi; Sato, Shuichiro; Saito, Takahisa; Kato, Jun-Ya; Shirota, Kazuhiko; Sato, Jun; Suzuki, Hiroyuki; Ohta, Shuji [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 15, p. 4162 - 4176]
[2]Current Patent Assignee: ASKA PHARMACEUTICAL CO., LTD. - US6511997, 2003, B1

23
[ 141-76-4 ]
[ 13121-99-8 ]
[ 438582-91-3 ]

Yield	Reaction Conditions	Operation in experiment
	In acetone	1 1-(2-carboxyethyl)-4-cyanomethyl-pyridinium Iodide EXAMPLE 1 1-(2-carboxyethyl)-4-cyanomethyl-pyridinium Iodide 4-cyanomethyl-pyridine 475 milligrams (0.004) mole were mixed with 1.0 gram of 3-iodopropionic acid (excess) in 100 ml round bottom flask. The flask was closed using a rubber septem and heated at 130 degrees Celsius using an oil bath for six hours. The flask was allowed to cool to ambient temperature and the reaction product was washed by triturating with ether. Acetone 30 ml was added and kept at room temperaturea for 12 hours. The precipitated product was filtered and washed with acetone, 755 mg (79%) of product was obtained.
	In acetone	1 1-(2-carboxyethyl)-4-cyanomethyl-pyridinium Iodide EXAMPLE 1 1-(2-carboxyethyl)-4-cyanomethyl-pyridinium Iodide 4-cyanomethyl-pyridine 475 milligrams (0.004) mole were mixed with 1.0 gram of 3-iodopropionic acid (excess) in 100 ml round bottom flask. The flask was closed using a rubber septem and heated at 130 degrees Celsius using an oil bath for six hours. The flask was allowed to cool to ambient temperature and the reaction product was washed by triturating with ether. Acetone 30 ml was added and kept at room temperatures for 12 hours. The precipitated product was filtered and washed with acetone, 755 mg (79%) of product was obtained.

Reference： [1]Current Patent Assignee: Theodoropulos, Spyros - US6617458, 2003, B2
[2]Current Patent Assignee: Theodoropulos, Spyros - US2004/47806, 2004, A1

24
[ 110-89-4 ]
[ 13121-99-8 ]
[ 4707-71-5 ]
2-(4-Pyridyl)-3-(9-phenanthryl)-2-propenenitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	In ethanol	9 2-(4-Pyridyl)-3-(9-phenanthryl)-2-propenenitrile Example 9 2-(4-Pyridyl)-3-(9-phenanthryl)-2-propenenitrile To a solution of 0.5 g (2.43 mmol) phenanthrene-9-carboxaldehyde in 40 ml absolute ethanol was added 0.375 g (2.43 mmol) 4-pyridylacetonitrile. HCl and 0.5 ml piperidine, and the reaction mixture was stirred and heated to reflux for 2 hours, at which time a yellow precipitate had formed. The reaction mixture was heated to reflux for an additional 2 hours, cooled to room temperature, and the solvent was partially evaporated. The mixture was partitioned between CH2 Cl2 and H2 O, washed with 5% NaHCO3, dried over anhydrous Na2 SO4, filtered, concentrated to give a yellow solid which was then flash chromatographed on silica gel. The material was loaded onto the column with CH2 Cl2 and eluted with EtOAc:hexane (1:1) to give 0.328 g (44% yield) of product as an amorphous yellow solid, m.p. 206°-208°.

Reference： [1]Current Patent Assignee: Yissum Research & Development (in: Hebrew University); HEBREW UNIVERSITY OF JERUSALEM - US5196446, 1993, A

25
[ 20781-06-0 ]
[ 13121-99-8 ]
pyridin-4-ylacetonitrile hydrochloride [ No CAS ]
6-Pyridin-4-yl-pyrido[2,3-d]pyrimidine-2,7-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In 2-ethoxy-ethanol; mineral oil;	EXAMPLE 109 6-Pyridin-4-yl-pyrido[2,3-d]pyrimidine-2,7-diamine To cooled (0 C.) 2-ethoxyethanol (13 mL) was added portionwise 0.30 g of sodium hydride (60% in mineral oil), and the suspension was stirred for 10 minutes. To this suspension was added 1.06 g of 4-pyridylaceto-nitrile hydrochloride, and the mixture was stirred at room temperature for 30 minutes. The neutralized solution of 4-pyridylacetonitrile in 2-ethoxyethanol was added to a reaction mixture containing sodium 2-ethoxyethoxide (prepared from 0.11 g of sodium hydride and 4.76 mL of 2-ethoxyethanol) and 0.9 g of <strong>[20781-06-0]2,4-diamino-5-pyrimidinecarboxaldehyde</strong>. The resulting mixture was heated at reflux for 2 hours, cooled, and the insoluble product washed with diethylether and ethyl acetate to afford the title compound; mp >340 C.; MS(CI). Analysis calculated for C12 H10 N6.0.05 H2 O: C, 60.27; H, 4.26; N, 35.14. Found: C, 60.35; H, 4.31; N, 34.75.

Reference： [1]Patent: US5733913,1998,A

26
[ 10429-82-0 ]
[ 14937-45-2 ]
[ 13121-99-8 ]
1-benzyl-4-cyano-4-(pyridin-4-yl)-piperidine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium hydroxide; In 1,4-dioxane;	Preparation 7 Synthesis of 4-(pyridin-4-yl)-piperidine-4-carboxylic acid amide and 4-(pyridin-4-yl)-piperidine-4-carboxylic acid amide hydrochloride Combine 4-pyridylacetonitrile (19.4 g, 125 mmol), N-benzyl-N,N-bis-(2-chloroethyl)amine hydrochloride (33.6 g, 125 mmol), and hexadecyltributylphosphonium bromide (3 g, 6 mmol) and a 50% aqueous sodium hydroxide solution. Heat to 100 C. After 1 hour, cool the reaction mixture to ambient temperature and repeatedly extract with diethyl ether. Extract the combined organic layers twice with an aqueous 10% hydrochloric acid solution (350 mL). Combine the aqueous layers and neutralize with an aqueous 50% sodium hydroxide solution. Again extract three times with diethyl ether, combine the organic layers, dry over MgSO4, and filter. Add a solution of hydrochloric acid in dioxane (60 mL 4M, 240 mmol) and evaporate in vacuo to give 1-benzyl-4-cyano-4-(pyridin-4-yl)-piperidine hydrochloride.

Reference： [1]Patent: US5824690,1998,A

27
[ 862856-15-3 ]
[ 13121-99-8 ]
Sym-N-(n-hexyl)-5-[2-cyano-2-(4-pyridyl)vinyl]triindole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With piperidine In tetrahydrofuran at 50℃; for 4h;	12 In a 50-ml, three-necked flask provided with a magnetic stirrer, a reflux condenser and a thermometer were placed 100 mg of Sym-N-(n-hexyl)-5-formyltriindole, 120 mg of 4-cyanomethylpyridine, 6.3 mg of piperidine and 15 ml of tetrahydrofuran (THF). A reaction was conducted at 50°C for 4 hours. After the completion of the reaction, the reaction mixture was subjected to silica gel column chromatography to obtain 131 mg of Sym-N-(n-hexyl)-[2-cyano-2-(4-pyridyl)vinyl]triindole. Yield: 91% Melting point: 255-260°CFAB-Mass (NBA, Positive): [(M+H)+] = 983IR (KBr, cm-1): 22101H-NMR (300 MHz, CDCl3), δ (ppm): 0.64 (t, J=7.2 Hz, 9H), 0.90-1.14 (m, 18H),1.82 (br, 6H), 4.81 (t, J=7.2 Hz, 6H),7.52 (d, J=8.7 Hz, 3H), 7.59-7.61 (m, 6H), 7.82 (s, 3H),7.96 (dd, J=1.0, 8.7 Hz, 3H), 8.63 (bs, 3H),8.71-8.73 (m, 6H)0.64 (t, J=7.2 Hz, 9H), 0.90-1.14 (m, 18H),1.82 (br, 6H), 4.81 (t, J=7.2 Hz, 6H),7.52 (d, J=8.7 Hz, 3H), 7.59-7.61 (m, 6H), 7.82 (s, 3H),7.96 (dd, J=1.0, 8.7 Hz, 3H), 8.63 (bs, 3H),8.71-8.73 (m, 6H)

Reference： [1]Current Patent Assignee: KUMIAI CHEMICAL INDUSTRY CO LTD - EP1717239, 2006, A1 Location in patent: Page/Page column 31

28
[ 111-83-1 ]
[ 534-17-8 ]
[ 13121-99-8 ]
[ 103284-57-7 ]

Yield	Reaction Conditions	Operation in experiment
69%	In acetonitrile	3 EXAMPLE 3 EXAMPLE 3 4-Pyridylacetonitrile (1.18 g, 0.01 mole) dissolved in acetonitrile (20 ml) was heated under reflux with n-octyl bromide (1.73 ml, 0.01 mole) and caesium carbonate (4 g) for 1 hour, filtered and concentrated. Elution from a column of silica gel as described in Example 1 gave 2-(4-pyridyl)decanonitrile (1.58 g, 69% yield).

Reference： [1]Current Patent Assignee: BOSTON SCIENTIFIC CORP - US4668689, 1987, A

29
[ 13121-99-8 ]
[ 72434-23-2 ]

Yield	Reaction Conditions	Operation in experiment
78.5%	With sodium carbonate; triphenylphosphine In ethanol	1 Preparation of 3-ethyl-3-(4-pyridyl)piperidine-2,6-dione EXAMPLE 1 Preparation of 3-ethyl-3-(4-pyridyl)piperidine-2,6-dione 4-Pyridylacetonitrile (5.6 g, 47.46 mmol) dissolved in ethanol (70 ml) was heated under reflux with rhodium chloride trihydrate (624 mg, 2.37 mmol), triphenylphosphine (3.11 g, 11.87 mmol) and anhydrous sodium carbonate (5.534 g, 52.2 mmol) for 20 hours, filtered and concentrated. Elution from a column (4.5, 35 cm) of silica gel (Merck 7734) with CHCl3 afforded a pure fraction of 2-(4-pyridyl)butyronitrile (5.44 g, 78.5% yield).

Reference： [1]Current Patent Assignee: BOSTON SCIENTIFIC CORP - US4668689, 1987, A

30
[ 13121-99-8 ]
[ 6674-22-2 ]
4-cyano-4-(pyridin-4-yl)pimelic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In acrylic acid methyl ester	1 (1) (1) 4-Cyano-4-(4-pyridyl)pimelic acid methyl ester To 10.4 g of methyl acrylate, there was added 0.2 g of 1,8-diazabicyclo[5.4.0]-7-undecene. Under ice-cooling, the mixture was maintained at 20 to 40°C while stirring. A solution of 14.2 g of 4-pyridylacetonitrile in 20.8 g of methyl acrylate was added. After 30 minutes, the water bath was removed and the reaction mixture was stirred at room temperature for additional one hour. Excess methyl acrylate was distilled off under reduced pressure. Purification by a silica gel column gave 35 g of 4-cyano-4-(4-pyridyl)pimelic acid methyl ester as an oily material. IR(Neat): 2950, 2230, 1740, 1590, 1430, 1200 cmmin1 NMR(100 MHz, CCl4, δ): 8.6 (2H. m); 7.4 (2H, m); 3.58 (6H,s); 1.9-2.7 (8H, m).

Reference： [1]Current Patent Assignee: MITSUI CHEMICALS,INC. - EP281661, 1988, A1

31
[ 13121-99-8 ]
[ 4637-24-5 ]
[ 493038-83-8 ]

Yield	Reaction Conditions	Operation in experiment
84.3%	In N,N-dimethyl-formamide at 125℃; for 18h;	50.1 (Z)-3-(dimethylamino)-2-(4-pyridyl)prop-2-enenitrile A mixture of 2-(4-pyridyl)acetonitrile (1.0 g, 8.46 mmol) in DMF-DMA (11.3 mL) and DMF was heated at 125° C. for 18 h. The reaction mixture was diluted with ice-water, extracted with EtOAc (6*). The combined organics were dried (Na2SO4), filtered and concentrated. The crude product was purified by silica flash chromatography (0-5% MeOH/DCM) to give the title compound (1.236 g, 84.3% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 8.38-8.27 (m, 2H), 7.80 (s, 1H), 7.32-7.22 (m, 2H), 3.26 (s, 6H). LCMS (ESI) m/z 174 [M+H+].
	With α,α,α-trifluorotoluene In N,N-dimethyl-formamide at 150℃; for 0.166667h; microwave irradiation;

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG; MORPHOSYS AG - US2015/65522, 2015, A1 Location in patent: Paragraph 0393; 0394
[2]Daniels, R. Nathan; Kim, Kwangho; Lebois, Evan P.; Muchalski, Hubert; Hughes, Mary; Lindsley, Craig W. [Tetrahedron Letters, 2008, vol. 49, # 2, p. 305 - 310]

32
[ 13121-99-8 ]
[ 292638-85-8 ]
[ 109173-38-8 ]

Yield	Reaction Conditions	Operation in experiment
88%	With N-benzyl-trimethylammonium hydroxide In <i>tert</i>-butyl alcohol for 4h; Reflux;

Reference： [1]Shen, Hong C.; Ding, Fa-Xiang; Deng, Qiaolin; Xu, Suoyu; Chen, Hsuan-shen; Tong, Xinchun; Tong, Vincent; Zhang, Xiaoping; Chen, Yuli; Zhou, Gaochao; Pai, Lee-Yuh; Alonso-Galicia, Magdalena; Zhang, Bei; Roy, Sophie; Tata, James R.; Berger, Joel P.; Colletti, Steven L. [Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 18, p. 5314 - 5320]

33
[ 109-65-9 ]
[ 13121-99-8 ]
[ 1285636-88-5 ]

Yield	Reaction Conditions	Operation in experiment
81%	Stage #1: pyridin-4-ylacetonitrile With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.666667h; Stage #2: 1-bromo-butane In tetrahydrofuran at -78 - 20℃; for 10h;

Reference： [1]Location in patent: scheme or table Tsao, Jing-Po; Tsai, Ting-Yueh; Chen, I-Chia; Liu, Hsing-Jang; Zhu, Jia-Liang; Tsao, Sheng-Wei [Synthesis, 2010, # 24, p. 4242 - 4250]

34
[ 100-39-0 ]
[ 13121-99-8 ]
[ 72434-28-7 ]

Yield	Reaction Conditions	Operation in experiment
91%	Stage #1: pyridin-4-ylacetonitrile With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.666667h; Stage #2: benzyl bromide In tetrahydrofuran at -78 - 20℃; for 10h;

Reference： [1]Location in patent: scheme or table Tsao, Jing-Po; Tsai, Ting-Yueh; Chen, I-Chia; Liu, Hsing-Jang; Zhu, Jia-Liang; Tsao, Sheng-Wei [Synthesis, 2010, # 24, p. 4242 - 4250]

35
[ 13121-99-8 ]
[ 106-95-6 ]
[ 72434-27-6 ]

Yield	Reaction Conditions	Operation in experiment
74%	Stage #1: pyridin-4-ylacetonitrile With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.666667h; Stage #2: allyl bromide In tetrahydrofuran at -78 - 20℃; for 10h;

Reference： [1]Location in patent: scheme or table Tsao, Jing-Po; Tsai, Ting-Yueh; Chen, I-Chia; Liu, Hsing-Jang; Zhu, Jia-Liang; Tsao, Sheng-Wei [Synthesis, 2010, # 24, p. 4242 - 4250]

36
[ 106-49-0 ]
[ 13121-99-8 ]
[ 1362165-59-0 ]

Yield	Reaction Conditions	Operation in experiment
76%	Stage #1: <i>p</i>-toluidine With hydrogenchloride; sodium nitrite In water Cooling in ice-salt bath; Stage #2: pyridin-4-ylacetonitrile With sodium acetate In ethanol; water Cooling in ice-salt bath;	4.1. Synthesis of arylhydrazonyl cyanide 2a-d and 4a-f General procedure: a well stirred solution of the base aromatic amine (0.1 mol) in 2 N hydrochloric acid (125 mL) was cooled in an ice-salt bath and diazotized with 1 N sodium nitrite solution (100 mL). The mixture was then tested for complete diazotization using starch iodide paper which gives a weak blue test. If the mixture does not give the test, more sodium nitrite was added dropwise until a positive test is obtained and the color is stable for few minutes. If, on the other hand, strong test for nitrite is obtained, a few drops of a dilute solution of the base hydrochloride are added until the nitrite test is nearly negative. The above cold diazonium solution was added slowly to a well stirred solution to cyanomethyl pyridine (0.1 mol) in ethanol (150 mL) containing 10% sodium acetate solution (50 mL) and the mixture was cooled in an ice-salt bath. After the addition of the diazonium salt solution, the reaction was tested for coupling reaction. A drop of the reaction mixture was placed on a filter paper and the colorless ring surrounding the spot dye was treated with a drop of an alkaline solution of a reactive coupler, such as a sodium salt of 3-hydroxy-2-naphthanilide. If unreacted diazonium salt is present, a dye is formed. The presence of unreacted coupler can be determined in a similar manner using a diazonium salt solution to test the colorless ring. After the coupling reaction was complete, the reaction mixture was stirred for 15 min at room temperature to coagulate the dye particles. The crude product was filtered, dried and recrystallized from ethanol to give N-arylpicolino and/or isonicotinohydrazonyl cyanide derivatives 2a-d and 4a-f (Table 2).