Name: 4556-23-4|Pyridine-4-thiol|97%
Brand: Ambeed
SKU: A676901
Rating: 93 (22 reviews)

1
[ 4556-23-4 ]
[ 2645-22-9 ]

Yield	Reaction Conditions	Operation in experiment
93%	With dihydrogen peroxide; In water; ethyl acetate; at 20℃; for 1.16667h;Green chemistry;	General procedure: In another study, a mixture of the VO-AMPD(at)SBA-15 (0.004 g), thiol (1 mmol) and H2O2 (0.4 mL) was stirred at room temperature in ethyl acetate (2 mL). The progress was monitored by TLC. After completion of the reaction, VO-AMPD(at)SBA-15 catalyst was separated from the mixture by filtration. Then products were extracted with ethyl acetate and dried, and the solvent was removed to give the pure disulfides.

Reference： [1]Journal of Chemical Research - Part S,2002,p. 547 - 549
[2]Research on Chemical Intermediates,2018,vol. 44,p. 4259 - 4276
[3]Phosphorus, Sulfur and Silicon and the Related Elements,2009,vol. 184,p. 1920 - 1923
[4]Phosphorus, Sulfur and Silicon and the Related Elements,2003,vol. 178,p. 1277 - 1281
[5]Journal of Chemical Research,2004,p. 286 - 287
[6]Journal of Chemical Research - Part S,2003,p. 28 - 29
[7]European Journal of Organic Chemistry,2014,vol. 2014,p. 4795 - 4804
[8]Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry,2013,vol. 43,p. 264 - 272
[9]Angewandte Chemie - International Edition,2016,vol. 55,p. 10781 - 10785
Angew. Chem.,2016,vol. 128,p. 10939 - 10943,5
[10]Chemische Berichte,1921,vol. 54,p. 1359
[11]Polish Journal of Chemistry,1992,vol. 66,p. 787 - 790
[12]Bulletin of the Chemical Society of Japan,1989,vol. 62,p. 616 - 617
[13]Journal of Sulfur Chemistry,2012,vol. 33,p. 187 - 195
[14]RSC Advances,2014,vol. 4,p. 33399 - 33407

2
[ 4556-23-4 ]
[ 74-88-4 ]
[ 22581-72-2 ]

Yield	Reaction Conditions	Operation in experiment
82%	With sodium hydroxide for 2h; Ambient temperature;
	Yield given;
	With sodium hydroxide	22 EXAMPLE 22 4-Methylsulfanylpyridine may be prepared by carrying out the procedure as described in Example 20, starting with 11.0 g of 4-mercaptopyridine, 105 cm3 of 1 N sodium hydroxide and 6.2 cm3 of methyl iodide. The crude oil obtained is purified by distillation under reduced pressure. 4.0 g of 4-methylsulfanylpyridine are obtained in the form of a white paste, b.p.=120° C./45 mm of mercury.

6.77 g (26.7 mmol, y. 53.5%)	In ethanol	9.A A. A. 4-Methylthiopyridine* STR176 Preparation of this compound was reported in King and Ware, J. Chem. Socl, 873(1939). The procedure, described in this reference was followed. 4-Mercaptopyridine (5.55 g, 50.0 mmol; Aldrich) was dissolved in boiling abs. EtOH (50 mL). The insoluble material was removed by filtration over Celite. The filtrate was heated to re-dissolve, and when it cooled to ca. 50° C., methyl iodide (3.17 mL, 51.0 mmol; Aldrich) was added at once. The mixture was cooled to crystallize. Filtration of the solid gave 6.77 g (26.7 mmol, y. 53.5%) of the title compound as the hydriodide: 1 Hmr (D2 O) δ: 2.70 (3H, s, --SCH3) and 7.65-7.77-8.35-8.48 ppm (4H, A2 B2 type, aromatic-Hs); ir (Nujol) νmax: 1615, 1585 (aromatic) and 780 cm-1; uv (H2 O) λmax: 227 (ε2.02104) and 298 nm (ε1.64*104).
	With potassium carbonate; triethylamine In dichloromethane at 0℃;
	With potassium hydroxide In methanol at 20℃; for 24h;	4.4. Preparation of pyridine derivatives 4-Mercaptopyridine (9 mmol) was dissolved in 100 mL of 1% methanolicKOH solution and one equivalent iodomethane was added. Thereaction mixture was stirred at room temperature for 24 h. After evaporatingthe solvent, the residue was extracted with CH2Cl2 and concentratedunder vacuum to give 4-methylthiopyridine.

Reference： [1]Dunne, Simon J.; Summers, Lindsay A.; Nagy-Felsobuky, Ellak I. von [Phosphorus, Sulfur and Silicon and the Related Elements, 1992, vol. 72, # 1-4, p. 103 - 120]
[2]Testaferri, L.; Tiecco, M.; Tingoli, M.; Chianelli, D.; Montanucci, M. [Synthesis, 1983, # 9, p. 751 - 755]
[3]Current Patent Assignee: SANOFI - US2001/27193, 2001, A1
[4]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US4552696, 1985, A
[5]Location in patent: experimental part Rioz-Martinez, Ana; De Gonzalo, Gonzalo; Pazmino, Daniel E. Torres; Fraaije, Marco W.; Gotor, Vicente [European Journal of Organic Chemistry, 2010, # 33, p. 6409 - 6416]
[6]Yang, Rui; Chen, Yu; Pan, Liangkun; Yang, Yanyan; Zheng, Qiang; Hu, Yue; Wang, Yuxi; Zhang, Liangren; Sun, Yang; Li, Zhongjun; Meng, Xiangbao [Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 17, p. 4886 - 4897]

3
[ 4556-23-4 ]
[ 116008-37-8 ]

Yield	Reaction Conditions	Operation in experiment
80%	With dihydrogen peroxide; sodium hydroxide In ethanol; water at 20℃; Schlenk technique; Inert atmosphere;
74%	With sodium hydroxide; dihydrogen peroxide In ethanol; water for 0.166667h; Ambient temperature;
11%	With dihydrogen peroxide; sodium hydroxide In methanol; water at 0 - 20℃; for 16h; Inert atmosphere;

Reference： [1]Wei, Jun; Liang, Huamin; Ni, Chuanfa; Sheng, Rong; Hu, Jinbo [Organic Letters, 2019]
[2]Kamiyama, Tsutomu; Enomoto, Saburo; Inoue, Masami [Chemical and pharmaceutical bulletin, 1988, vol. 36, # 7, p. 2652 - 2653]
[3]Davis, Christopher J.; De Gombert, Antoine; McKay, Alasdair I.; Wheelhouse, Katherine M.; Willis, Michael C. [Journal of the American Chemical Society, 2020]

4
[ 2645-22-9 ]
Thiophosphoric acid S-octyl ester O-((1S,2R,3R,4S,5S,6R)-2,3,4,5,6-pentahydroxy-cyclohexyl) ester [ No CAS ]
[ 4556-23-4 ]
[ 41158-67-2 ]

Reference： [1]Journal of Organic Chemistry,1996,vol. 61,p. 8016 - 8023

5
[ 4556-23-4 ]
[ 6940-78-9 ]
[ 142792-77-6 ]

Yield	Reaction Conditions	Operation in experiment
89.7%	With triethylamine In ethanol; chloroform	R.3 Synthesis of 4-(4-chlorobutylthio)pyridine REFERENCE EXAMPLE 3 Synthesis of 4-(4-chlorobutylthio)pyridine To a suspension of 33.35 g (0.30 mol) of 4-mercaptopyridine and 51.44 g (0.30 mol) of 1-bromo-4-chlorobutane in 500 ml of ethanol, 41.9 ml (0.30 mol) of triethylamine was added, and the mixture was stirred at room temperature for 5 hours. The solvent was distilled off and chloroform was added to the residue. The mixture was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off and the residue was purified by column chromatography (eluent: ethyl acetate/n-hexane =1:1) to give 54.27 g of the desired compound (89.7% yield, colorless oil). NMR (200 MHz, CDCl3) δ: 1.92 (4H, m), 3.02 (2H, t, J=6.8 Hz), 3.59 (2H, t, J=6.2 Hz), 7.12 (2H, dd, J=4.6, 1.6 Hz), 8.40 (2H, dd, J=4.0, 1.6 Hz).
78%	With potassium carbonate In acetone

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US5246948, 1993, A
[2]Boschelli, Diane H.; Connor, David T.; Lesch, Mark E.; Schrier, Denis J. [Bioorganic and Medicinal Chemistry, 1996, vol. 4, # 4, p. 557 - 562]

6
[ 4556-23-4 ]
[ 5460-29-7 ]
[ 116741-00-5 ]

Yield	Reaction Conditions	Operation in experiment
48%	With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 3.5h;	3.2. General procedure (A) for preparation of phthalimide derivatives: preparation of 2-[2'-(pyridin-2-sulfanyl)ethyl]-1H-isoindole-1,3(2H)-dione (3a) General procedure: The phthalimides 3a-d were prepared by modifying the procedure outlined by Boschelli et al.25 as described below for the preparation of phthalimide 3a.N-(2-Bromoethyl)phthalimide (6.86 g, 27.0 mmol) and K2CO3 (6.84 g, 49.5 mmol) were added to a solution of 2-mercaptopyridine (2.50 g, 22.5 mmol) in dry acetone (75 mL). The resulting mixture was stirred at reflux for 2 h and then allowed to cool to ambient temperature. The solid was collected by filtration and washed with EtOAc. The filtrate was concentrated in vacuo to give a brown oil. A precipitate formed on standing and the resulting mixture was triturated with 40% EtOAc/hexane to afford the title compound 3a as a white solid (4.10 g, 64%).
34%	With potassium carbonate In acetone for 0.333333h; Heating;

Reference： [1]Location in patent: experimental part Mountford, Simon J.; Campi, Eva M.; Robinson, Andrea J.; Hearn, Milton T.W. [Tetrahedron, 2011, vol. 67, # 2, p. 471 - 485]
[2]Boschelli, Diane H.; Connor, David T.; Lesch, Mark E.; Schrier, Denis J. [Bioorganic and Medicinal Chemistry, 1996, vol. 4, # 4, p. 557 - 562]

7
[ 2645-22-9 ]
[ 4556-23-4 ]

Reference： [1]Journal of the Chemical Society. Perkin Transactions 2 (2001),2001,p. 13 - 17
[2]Journal of the American Chemical Society,2017,vol. 139,p. 9136 - 9139

8
[ 4556-23-4 ]
[ 7496-46-0 ]
[ 658072-05-0 ]

Reference： [1]Dalton Transactions,2003,p. 4742 - 4748

9
[ 4556-23-4 ]
[ 7733-29-1 ]
[ 657411-69-3 ]

Reference： [1]Journal of Organic Chemistry,2005,vol. 70,p. 7512 - 7519
[2]Tetrahedron,2003,vol. 59,p. 10541 - 10549

10
[ 4556-23-4 ]
[ 892-48-8 ]
(2R,3R,4S,5S)-2-(6-Amino-purin-9-yl)-5-(pyridin-4-ylsulfanylmethyl)-tetrahydro-furan-3,4-diol [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 2829 - 2833

11
[ 4556-23-4 ]
[ 18226-42-1 ]
[ 862014-52-6 ]

Yield	Reaction Conditions	Operation in experiment
90%	With triethylamine In acetonitrile at 0℃; for 18h;
	With triethylamine In acetonitrile at 0 - 20℃; for 12h;	3.2. Synthesis of Ligand (L) and Adsorbent (MOF 1) The L and MOF 1 were prepared according to our paper and reported previously [30].Specifically, a mixture of 4-mercaptopyridine (15 mmol, 1.67 g), 1,3,5-tris(bromomethyl)benzene(5 mmol, 1.78 g) and Et3N (20 mmol, 2.0 g) in acetonitrile (30 mL) was stirred at 0 C for 12 h, and thenslowly warmed to room temperature. After the reaction was completed, the reaction solution wasfiltered to obtain a solid, and then washed with acetonitrile, deionized water, and ether three times.The residue was vacuum dried to obtain L. After obtaining the organic L, the acetonitrile solution(1.5 mL) of ZnCl2 (0.030 mmol) was layered on a DMF solution (1.5 mL) of the L (0.02 mmol) in a testtube. Then 1.5 mL of 1:1 acetonitrile/DMF buer solution was layered between the top and bottomlayers to allow slow diusion for 3 days. Following this, MOF 1 was obtained.

Reference： [1]Bray, David J.; Liao, Li-Ling; Antonioli, Bianca; Gloe, Karsten; Lindoy, Leonard F.; McMurtrie, John C.; Wei, Gang; Zhang, Xiao-Yi [Dalton Transactions, 2005, # 12, p. 2082 - 2083]
[2]Di, Bin; Li, Jing-Jing; Li, Kan; Ma, Ying; Zhao, Ni [Molecules, 2020, vol. 25, # 6]

12
[ 4556-23-4 ]
4-[(2-fluoro-4-nitrophenyl)sulfanyl]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With potassium carbonate In DMF (N,N-dimethyl-formamide); 3,4-difluoronitrobenzene at 40℃; for 3h;	VII Example VII; 4- [ (2-fluoro-4-nitorphenyl)]sulfanyl]pyridine 21 g (188.9 mmol) 4-Mercaptopyridin, 30.05 g (188.9 mmol) 3, [4-DIFLUOMITROBENZOL] und 60.05 g (434.5 mmol) Kaliumcarbonat werden in Dimethylformamid gelöst und 3 Stunden bei [40°C] gerührt. Anschließend wird die Reaktionslösung mit 500 ml Ethylacetat und 300 ml Wasser verdünnt. Die wässrige Phase wird fünfmal mit je 100 ml Ethylacetat extrahiert. Die vereinigten organischen Phasen werden mit 200 ml gesättigter Natriumchloridlösung gewaschen, über Natriumsulfat getrocknet und im Vakuum einrotiert. Der Rückstand wird über eine MPLC gereinigt (Laufmittel : Ethylacetat-Cyclohexan 1 : 1) Es werden 37.3 g (79 % d. Th. ) Produkt erhalten. [IH-NMR] (300 MHz, DMSO-d6) : [8] = 7.28 (dd, 2H), 7.79 (t, 1H), 8.15 (dd, 1H), 8.30 (dd, [1H),] 8.50 (dd, 2H) LC-MS (Methode 4) : Rt = 2.68 min MS (ESIpos) : [M/Z= 251 (M+H) +]

Reference： [1]Current Patent Assignee: BAYER AG - WO2003/106450, 2003, A1 Location in patent: Page column 42,43

13
[ 4556-23-4 ]
[ 400-74-8 ]
[ 228401-26-1 ]

Yield	Reaction Conditions	Operation in experiment
54%	With potassium carbonate; In N,N-dimethyl-formamide;	Step 1. 3-(Trifluoromethyl)-4-(4-pyridinylthio)nitrobenzene A solution of 4-mercaptopyridine (2.8 g, 24 mmoles), 2-fluoro-5-nitrobenzotrifluoride (5 g, 23.5 mmoles), and potassium carbonate (6.1 g, 44.3 mmoles) in anhydrous DMF (80 mL) was stirred at room temperature and under argon overnight. TLC showed complete reaction. The mixture was diluted with Et2O (100 mL) and water (100 mL) and the aqueous layer was back-extracted with Et2O (2*100 mL). The organic layers were washed with a saturated NaCl solution (100 mL), dried (MgSO4), and concentrated under reduced pressure. The solid residue was triturated with Et2O to afford the desired product as a tan solid (3.8 g, 54percent): TLC (30percent EtOAc/70percent hexane) Rf 0.06; 1H-NMR (DMSO-d6) delta 7.33 (dd, J=1.2, 4.2 Hz, 2H), 7.78 (d, J=8.7 Hz, 1H), 8.46 (dd, J=2.4, 8.7 Hz, 1H), 8.54-8.56 (m, 3H).
54%	With potassium carbonate; In N,N-dimethyl-formamide;	Step 1 3-(Trifluoromethyl)-4-(4-pyridinylthio)nitrobenzene A solution of 4-mercaptopyridine (2.8 g, 24 mmoles), 2-fluoro-5-nitrobenzotrifluoride (5 g, 23.5 mmoles), and potassium carbonate (6.1 g, 44.3 mmoles) in anhydrous DMF (80 mL) was stirred at room temperature and under argon overnight. TLC showed complete reaction. The mixture was diluted with Et2O (100 mL) and water (100 mL) and the aqueous layer was back-extracted with Et2O (2*100 mL). The organic layers were washed with a saturated NaCl solution (100 mL), dried (MgSO4), and concentrated under reduced pressure. The solid residue was triturated with Et2O to afford the desired product as a tan solid (3.8 g, 54percent): TLC (30percent EtOAc/70percent hexane) R.f. 0.06; 1H-NMR (DMSO-d6) delta 7.33 (dd, J=1.2, 4.2 Hz, 2H), 7.78 (d, J=8.7 Hz, 1H), 8.46 (dd, J=2.4, 8.7 Hz, 1H), 8.54-8.56 (m, 3H).
54%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	Step 1. 3-(Trifluoromethyl)-4-(4-pyridinylthio)nitrobenzene A solution of 4-mercaptopyridine (2.8 g, 24 mmoles), 2-fluoro-5-nitrobenzotrifluoride (5 g, 23.5 mmoles), and potassium carbonate (6.1 g, 44.3 mmoles) in anhydrous DMF (80 ml) was stirred at room temperature and under argon overnight. TLC showed complete reaction. The mixture was diluted with Et2O (100 mL) and water (100 mL) and the aqueous layer was back-extracted with Et2O (2*100 muL). The organic layers were washed with a saturated NaCl solution (100 ml), dried (MgSO4), and concentrated under reduced pressure. The solid residue was triturated with Et2O to afford the desired product as a tan solid (3.8 g, 54percent): TLC (30percent EtOAc/70percent hexane) Rf 0.06; 1H-NMR (DMSO-d6) delta 7.33 (dd, J=1.2, 4.2 Hz, 2H), 7.78 (d, J=8.7 Hz, 1H), 8.46 (dd, J=2.4, 8.7 Hz, 1H), 8.54-8.56 (m, 3H).

54%	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃;	A solution of 4-mercaptopyridine (2.8 g, 24 mmoles), 2-fluoro-5-nitrobenzotrifluoride (5 g, 23.5 mmoles), and potassium carbonate (6.1 g, 44.3 mmoles) in anhydrous DMF (80 mL) was stirred at room temperature and under argon overnight. TLC showed complete reaction. The mixture was diluted with Et2O (100 mL) and water (100 mL) and the aqueous layer was back-extracted with Et2O (2 x 100 mL). The organic layers were washed with a saturated NaCl solution (100 mL), dried (MgSO4), and concentrated under reduced pressure. The solid residue was triturated with Et2O to afford the desired product as a tan solid (3.8 g, 54percent): TLC (30percent EtOAc/70percent hexane) Rf 0.06;1H-NMR (DMSO-d6) ? 7.33 (dd, J=1.2, 4.2 Hz, 2H), 7.78 (d, J=8.7 Hz, 1H), 8.46 (dd,J=2.4, 8.7Hz, 1H), 8.54-8.56 (m, 3H).
54%	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃;	A13b. General Method for Substituted Aniline Formation via Nitroarene Formation Through Nucleophilic Aromatic Substitution, Followed by Reduction; [] Step 1. 3-(Trifluoromethyl)-4-(4-pyridinylthio)nitrobenzene: A solution of 4-mercaptopyridine (2.8 g, 24 mmoles), 2-fluoro-5-nitrobenzotrifluoride (5 g, 23.5 mmoles), and potassium carbonate (6.1 g, 44.3 mmoles) in anhydrous DMF (80 mL) was stirred at room temperature and under argon overnight. TLC showed complete reaction. The mixture was diluted with Et2O (100 mL) and water (100 mL) and the aqueous layer was back-extracted with Et2O (2 x 100 mL). The organic layers were washed with a saturated NaCl solution (100 mL), dried (MgSO4), and concentrated under reduced pressure. The solid residue was triturated with Et2O to afford the desired product as a tan solid (3.8 g, 54percent): TLC (30percent EtOAc/70percent hexane) Rf 0.06; 1H-NMR (DMSO-d6) delta 7.33 (dd, J=1.2, 4.2 Hz, 2H), 7.78 (d, J=8.7 Hz, 1H), 8.46 (dd, J=2.4, 8.7Hz, 1H), 8.54-8.56 (m, 3H).
54%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	B3b. General Method for Substituted Aniline Formation Via Nitroarene Formation Through Nucleophilic Aromatic Substitution, Followed by Reduction; Step 1. 3-(Trifluoromethyl)-4-(4-pyridinylthio)nitrobenzene; A solution of 4-mercaptopyridine (2.8 g, 24 mmoles), 2-fluoro-5-nitrobenzotrifluoride (5 g, 23.5 mmoles), and potassium carbonate (6.1 g, 44.3 mmoles) in anhydrous DMF (80 mL) was stirred at room temperature and under argon overnight. TLC showed complete reaction. The mixture was diluted with Et2O (100 mL) and water (100 mL) and the aqueous layer was back-extracted with Et2O (2.x.100 mL). The organic layers were washed with a saturated NaCl solution (100 mL), dried (MgSO4), and concentrated under reduced pressure. The solid residue was triturated with Et2O to afford the desired product as a tan solid (3.8 g, 54percent): TLC (30percent EtOAc/70percent hexane) Rf 0.06; 1H-NMR (DMSO-d6) delta 7.33 (dd, J=1.2, 4.2 Hz, 2H), 7.78 (d, J=8.7 Hz, 1H), 8.46 (dd, J=2.4, 8.7 Hz, 1H), 8.54-8.56 (m, 3H).
54%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	Step 1. 3-(Trifluoromethyl)-4-(4-pyridinylthio)nitrobenzene A solution of 4-mercaptopyridine (2.8 g, 24 mmoles), 2-fluoro-5-nitrobenzotrifluoride (5 g, 23.5=rnoles), and potassium carbonate (6.1 g, 44.3 mmoles) in anhydrous DNIF (80 mL) was stirred at room temperature and under argon overnight. TLC showed complete reaction. The mixture was diluted with Et2O (100 mL) and water (100 mL) and the aqueous layer was back-extracted with Et2O (2*100 mL). The organic layers were washed with a saturated NaCl solution (100 mL), dried (MgSO4), and concentrated under reduced pressure. The solid residue was triturated with Et2O to afford the desired product as a tan solid (3.8 g, 54percent): TLC (30percent EtOAc/70percent hexane) Rf 0.06; 1H-NMR (DMSO-d6) delta 7.33 (dd, J=1.2, 4.2 Hz, 2H), 7.78 (d, J=8.7 Hz, 1H), 8.46 (dd, J=2.4, 8.7 Hz, 1H), 8.54-8.56 (m, 3H).
54%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere;	Step 1.3-(Trifluoromethyl)-4-(4-pyridinylthio)nitrobenzene A solution of 4-mercaptopyridine (2.8 g, 24 mmoles), 2-fluoro-5-nitrobenzotrifluoride (5 g, 23.5 mmoles), and potassium carbonate (6.1 g, 44.3 mmoles) in anhydrous DMF (80 mL) was stirred at room temperature and under argon overnight. TLC showed complete reaction.The mixture was diluted with Et2O (100 mL) and water (100 mL) and the aqueous layer was back-extracted with Et2O (2*100 mL).The organic layers were washed with a saturated NaCl solution (100 mL), dried (MgSO4), and concentrated under reduced pressure.The solid residue was triturated with Et2O to afford the desired product as a tan solid (3.8 g, 54percent): TLC (30percent EtOAc/70percent hexane) Rf 0.06; 1H-NMR (DMSO-d6) delta 7.33 (dd, J=1.2, 4.2 Hz, 2H), 7.78 (d, J=8.7 Hz, 1H), 8.46 (dd, J=2.4, 8.7 Hz, 1H), 8.54-8.56 (m, 3H).
54%	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃;	A solution of 4-mercaptopyridine (2.8 g, 24 mmoles), 2-fluoro-5-nitrobenzotrifluoride (5 g, 23.5 mmoles), and potassium carbonate (6.1 g, 44.3 mmoles) in anhydrous DMF (80 mL) was stirred at room temperature and under argon overnight. TLC showed complete reaction. The mixture was diluted with Et2O (100 mL) and water (100 mL) and the aqueous layer was back-extracted with Et2O (2 x 100 mL). The organic layers were washed with a saturated NaCl solution (100 mL), dried (MgSO4), and concentrated under reduced pressure. The solid residue was triturated with Et2O to afford the desired product as a tan solid (3.8 g, 54percent): TLC (30percent EtOAc/70percent hexane) Rf 0.06;1H-NMR (DMSO-d6) delta 7.33 (dd, J=1.2, 4.2 Hz, 2H), 7.78 (d, J=8.7 Hz, 1H), 8.46 (dd,J=2.4, 8.7Hz, 1H), 8.54-8.56 (m, 3H).

Reference： [1]Patent: US2002/65296,2002,A1
[2]Patent: US2004/102636,2004,A1
[3]Patent: US2008/269265,2008,A1 .Location in patent: Page/Page column 14
[4]Patent: EP1449834,2004,A2 .Location in patent: Page 23
[5]Patent: EP1042305,2005,B1 .Location in patent: Page/Page column 28
[6]Patent: US2007/244120,2007,A1 .Location in patent: Page/Page column 17
[7]Patent: US2003/207914,2003,A1 .Location in patent: Page/Page column 8-9
[8]Patent: US2012/46290,2012,A1 .Location in patent: Page/Page column 17
[9]Patent: EP1047418,2005,B1 .Location in patent: Page/Page column 28

14
[ 4556-23-4 ]
[ 459-57-4 ]
C₁₂H₁₂N₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
37%	Stage #1: pyridine-4-thiol; 4-fluorobenzaldehyde With potassium carbonate In 1-methyl-pyrrolidin-2-one at 70℃; for 3h; Stage #2: With sodium tetrahydroborate In methanol at 20℃; for 3h; Stage #3: With ammonia; phosphorus tribromide more than 3 stages;	86.a Example 86 6-Methyl-2-oxo-N-[[4-(4-pyridinylsulfonyl)phenyl]methyl]-1-[3- (trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxyamide; a) L-F4- (PYNDIN-4-YLSULFONYDPHENYL1METHANAMINE To a mixture of 4-mercaptopyridine (0.8 g, 7.2 mmol) and K2CO3 (2.0 g, 14.4 mmol) in NMP, 4-fluorobenzaldehyde (0.99 g, 8.0 mmol) was added. The mixture was then stirred at 70 °C for 3 h. After cooling, the reaction mixture was diluted with water (5. 0 ml) and extracted with EtOAc. The organic solvent was evaporated and the residue dissolved in methanol. Sodium borohydride (0.57 g, 15 mmol) was added and the mixture stirred for 3 h at room temperature. After addition of water, the methanol was removed in vacuo and the residue extracted with CH2C12. The organic phase was dried over MGSO4, filtered, and evaporated and the residue was dissolved in toluene (10 ml). The toluene solution was heated to 40 °C, phosphorus tribromide (0.25 g, 0.92 mmol) was added and the temperature increased to 100 °C for 30 minutes. After cooling, water (50 ml) was added and the mixture extracted with EtOAc. The organic phase was evaporated, the residue dissolved in methanol and slowly added to a mixture of 25% ammonia (15 ml) in methanol (10 ML). After stirring for 3 h at room temperature the subtitle compound was obtained. (0.30 g, 37%) as a white solid. APCI-MS M/Z : 217.2 [MH+]

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2004/43924, 2004, A1 Location in patent: Page 168-169

15
[ 4556-23-4 ]
[ 75-26-3 ]
[ 794533-49-6 ]

Yield	Reaction Conditions	Operation in experiment
63%	Stage #1: pyridine-4-thiol; isopropyl bromide With potassium carbonate at 20℃; Stage #2: With hydrogenchloride In diethyl ether	35 4-Isopropylsulfanylpyridine A mixture of 4-mercaptopyridine (7 g, 63 mmol), 2-bromopropane (7.0 ml, 75.6 mmol), and potassium carbonate (10.2 g, 73.7 mmol) was stirred at room temperature for 6 hours and left overnight. The solid was filtered off and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica gel (i-hexane:ethyl acetate) to give the title product (7.4 g, 63%). The hydrochloride salt was prepared by treatment of the title compound with ethereal HCl. [0253] δH (360 MHz, CDCl3): 8.40 (2H, d, J 5.9 Hz), 7.12 (2H, d, J 6.3 Hz), 3.60 (1H, heptet, J 6.7 Hz), 1.39 (6H, d, J 6.7 Hz); m/z (ES+) 154 (M+H)+.

Reference： [1]Current Patent Assignee: MERCK & CO INC - US2004/229864, 2004, A1 Location in patent: Page/Page column 10

16
[ 4556-23-4 ]
[ 636-98-6 ]
[ 746630-21-7 ]

Yield	Reaction Conditions	Operation in experiment
86.5%	With potassium carbonate In N,N-dimethyl-formamide at 100 - 120℃; for 4h;	Method of Preparation of 4-(Pyridin-4-ylsulfinyl)nitrobenzene (4b) To a solution of 4-mercaptopyridine 3 (1.8 mmol) in dimethylformamide was added anhydrous potassium carbonate (3.6 mmol) and 4-iodonitrobenzene (1.9 mmol) and heated at 100-120°C for 4 hours. The reaction mixture was cooled, diluted with ethyl acetate and washed with water. The organic layer was again washed with brine and dried over anhydrous sodium sulphate. The organic solvent was evaporated and the crude product obtained was used in subsequent reaction without purification.
54%	In DMF (N,N-dimethyl-formamide) at 128℃; for 5h;	W.1 First, 4- (4-NITRO-PHENYLTHIO)-PYRIDINE, which has the structural formula was prepared. 1-LODO-4-NITRO-BENZENE (ALDRICH, 1.24 g, 5.00 MMOL) and pyridine-4-thiol (Aldrich, 0.55 g, 5.0 MMOL) in DMF was heated at 128 °C for 5 hours. The solvent was removed under reduced pressure and ethyl acetate added. The solution was washed with 0.1 N NAOH, dried over MGS04, and evaporated. Purification via column chromatography gave 0.62 G (54% yield) of a yellow solid, which was used without any further purification. 1HNMR : 8 8.52 (2H, d, J = 6.5 Hz), 8.22 (2H, d, J = 8.6 Hz), 7.56 (2H, d, J = 8. 6 HZ), 7.20 (2H, d, J = 6. 5 HZ). 4-(4-LSOTHIOCYANATO-PHENYLTHIO)-PYRIDINE, which has the structural formula was prepared as follows. A solution OF 4- (4-NITRO-PHENYLTHIO)- pyridine (500 mg, 2.15 MMOL) in concentrated HCI (0.5 mL) and methanol (50 mL) was hydrogenated at 20 psi in the presence of 10% Pd/C for 2hours, then filtered through Celite. The filtrate was concentrated (free base previously known, mp 169-71 C, see Takahashi, et al, Pharm Bull., 30 (1954)), immediately a portion (0.46 g, 2.0 MMOL) was combined with Et3N (0.5 g, 5 MMOL) and CH2CI2, and cooled to 0 C. Thiophosgene (0.26 g, 2.2 MMOL) was added dropwise and the mixture allowed to warm to ambient temperature over 1 hours. More CH2Cl2 was added, washed with sat. aq. NAHCO3 and brine, dried over MGS04, and concentrated in vacuo to give a crude product, which was purified by column chromatography to provide 0.20 G (40% yield) of a yellow solid, which was used without any further purification. H NMR : 8 8. 35 (2H, d, J = 6. 5 HZ), 7.54 (2H, d, J = 8. 6 HZ), 7.26 (2H, d, J = 8. 6 HZ), 6.95 (2H, d, J = 6.5 Hz). FTIR (KBR) : 2180 (s) CM~1. The title compound was prepared in the same manner that was described for 4- [4- AMINO-5- (2, 6-DIFLUORO-BENZOYL)-THIAZOL-2-YLAMINO]-BENZENESULFONYL FLUORIDE from Example A (1). 4-(4-Isothicyanato-phenylthio)-pyridine and 2-bromo-2', 6'-dichloro-acetophenone (from World Patent Application WO 99/21845 and MLOTKOWSKA, et AL., Pol. J. Chem. , 55,631- 642 (1981) ) gave 10 mg (3%) of a yellow solid. H NMR : 8 8. 36 (2H, d, J = 6. 5 HZ), 7.50 (2H, d, J = 8. 6 HZ), 7.42 (2H, d, J = 9. 2 HZ), 7.32 (2H, d, J = 8. 6 HZ), 7.24 (1H, m), 6.92 (2H, d, J = 6. 5 HZ). HRFABMS calcd. for C21H15N4OS2Cl2 (M+H+) : 473.0064. Found: 473.0070.

Reference： [1]Kulkarni, Ravindra G.; Laufer, Stefan; Mangannavar, Chandrashekhar; Garlapati, Achaiah [Medicinal Chemistry, 2013, vol. 9, # 2, p. 213 - 221]
[2]Current Patent Assignee: PFIZER INC - WO2004/72070, 2004, A1 Location in patent: Page 84-85

17
[ 4556-23-4 ]
[ 5402-20-0 ]

Yield	Reaction Conditions	Operation in experiment
	With dihydrogen peroxide; In H20; acetic acid; at 80℃; for 1.5h;	4-Mercaptopyridine (500 mg) was dissolved in glacial acetic acid (18ml_), followed by the addition of 35% hydrogen peroxide (6ml_). The solution was warmed at 80 deg C for 90 min. and then concentrated to dryness. The product was re-crystallized from methanol :water, dried in a vacuo and used in the next step.
	With dihydrogen peroxide; acetic acid; In water; at 80℃; for 1.5h;	4.42 Pyridine 4-sulphonic acid; 4-Mercaptopyridine (500 mg) was dissolved in glacial acetic acid (18 ml), followed by the addition of 35% hydrogen peroxide (6 ml). The solution was warmed at 80 0C for 90 min. and <n="55"/>then concentrated to dryness. The product was re-crystallized from methanokwater, dried in a vacuo and used in the next step.

Reference： [1]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 1307 - 1324
[2]Patent: WO2006/64286,2006,A1 .Location in patent: Page/Page column 118
[3]Patent: WO2007/144379,2007,A1 .Location in patent: Page/Page column 53-54

18
[ 4556-23-4 ]
[ 773071-03-7 ]
[ 937709-24-5 ]

Yield	Reaction Conditions	Operation in experiment
67%	With triethylamine In dichloromethane at 20℃; for 12h;	4 Subsequently, methyl 5-bromo-2-[3-(chloromethyl)benzoyl]aminobenzoate (1.5 g) was dissolved in anhydrous methylene chloride. Triethylamine (2.0 ml) and 4-mercaptopyridine (compound B') (880 mg) were added to the solution at room temperature, and the mixture was stirred at that temperature for 12 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution, was dried over sodium sulfate, and was then concentrated. Diethyl ether was added to the residue for crystallization. The crystals were filtered through Kiriyama Rohto (21 mm) and were washed with diethyl ether to give methyl 5-bromo-2-(3-[(4-pyridylsulfanyl)methyl]benzoylamino)benzoate (1.20 g, yield 67%) as a useful intermediate.

Reference： [1]Current Patent Assignee: Kyowa Kirin (in: Kirin Holdings); KIRIN HOLDINGS CO., LTD. - EP1614676, 2006, A1 Location in patent: Page/Page column 61

19
[ 4556-23-4 ]
[ 86265-88-5 ]
4-chloro-3-(pyridin-4-ylthio)-benzaldehyde dimethyl acetal [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In N-methyl-acetamide; methanol; dichloromethane; water; mineral oil;	(D) A solution of 222 mg of 4-mercaptopyridine in 2 ml of anhydrous dimethylformamide was added dropwise to a suspension of 80 mg of a 60% dispersion of sodium hydride in mineral oil in 15 ml of anhydrous dimethylformamide at below 5 C. After 50 minutes a solution of 0.5 g of <strong>[86265-88-5]3-bromo-4-chlorobenzaldehyde</strong> in 1 ml of anhydrous dimethylformamide was added dropwise and the mixture was heated at 150 C. for 29 hours. The mixture was then cooled to below 5 C. and 5 ml of a 1M solution of hydrochloric acid were added cautiously. The mixture was diluted with 50 ml of water and then extracted twice with 100 ml of ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulphate, filtered and evaporated to dryness. The residue was purified by column chromatography on silica gel using methanol/dichloromethane (5:95) as the eluent to give 120 mg of 4-chloro-3-(4-pyridylthio)-benzaldehyde dimethyl acetal as a pale yellow oil, mass spectrum (CI) m/e 296 [M+].

Reference： [1]Patent: US5969139,1999,A

20
[ 4556-23-4 ]
[ 627-18-9 ]
[ 156009-54-0 ]

Yield	Reaction Conditions	Operation in experiment
83.9%	With sodium hydroxide; triethylamine In dichloromethane; water	51.i i) i) Synthesis of 4-(3-hydroxypropylthio)pyridine In 100 ml of methylene chloride were dissolved 11.1 g (100 mmol) of 4-mercaptopyridine and 13.9 ml (100 mmol) of triethylamine, and 9.04 ml (100 mmol) of 3-bromo-1-propanol was added. The mixture was stirred at room temperature for 2 hours. The reaction mixture was washed with a 1N aqueous solution of sodium hydroxide and water and dried. Then the solvent was distilled off. The residue was purified by column chromatography (eluent: ethyl acetate) to obtain 14.2 g of the desired compound (yield: 83.9%, yellow oil). NMR (200MHz, CDCl3) δ:1.97 (2 H, quint., J=7 Hz), 3.12 (2 H, t, J=7 Hz), 3.81 (2 H, t, J=7 Hz), 7.14 (2 H, dd, J=5, 2 Hz), 8.37 (2 H, dd, J=5, 2 Hz). IR (neat)cm-1: 3350, 2940, 1580.
62.9%	With sodium hydroxide; triethylamine In dichloromethane; water	73.i i) i) Synthesis of 4-(3-hydroxypropylthio)pyridine In 250 ml of methylene chloride was dissolved 22.2 g (200 mmol) of 4-mercaptopyridine and 27.9 ml (200 mmol) of triethylamine. Thereto was added 18.1 g (200 mmol) of 3-bromo-1-propanol. The mixture was stirred at room temperature for 3 hours. The reaction mixture was washed with a 1N aqueous solution of sodium hydroxide and water and dried. Then the solvent was distilled off. The residue was purified by column chromatography (eluent: ethyl acetate) to obtain 21.3 g of the desired compound (yield: 62.9%, yellow oil). NMR (200 MHz, CDCl3) δ:1.97 (2 H, quint., J=7 Hz), 3.12 (2 H, t, J=7 Hz), 3.81 (2 H, t, J=7 Hz), 7.14 (2 H, dd, J=5, 2 Hz), 8.37 (2 H, dd, J=5, 2 Hz). IR (neat)cm-1: 3350, 2940, 1580.

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US5246948, 1993, A
[2]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US5246948, 1993, A

21
[ 4556-23-4 ]
[ 3569-99-1 ]
4-(3-picolinoylaminomethylthio)pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
15.9%	With trifluoroacetic acid; In ethanol; water;	EXAMPLE 138 Synthesis of 4-(3-picolinoylaminomethylthio)pyridine To a mixture of 1.11 g (10 mmol) of 4-mercaptopyridine and 1.52 g (10 mmol) of N-(hydroxymethyl)nicotinamide, 30 ml of trifluoroacetic acid was added, and the mixture was stirred at room temperature for 1 hour. The solvent was distilled off and 30 ml of ethanol was added to the residue. The solvent was distilled off and water was added to the residue. The mixture was neutralized with saturated aqueous sodium bicarbonate, followed by extraction with chloroform. After washing with saturated saline, the extract was dried over anhydrous magnesium sulfate. The solvent was distilled off and the residue was purified by column chromatography (eluent: ethyl acetate/ethanol =5:1) to give 390 mg of the desired compound (15.9% yield, yellow solid). NMR (200 MHz, CDCl3) delta: 5.06 (2H, d, J=6 Hz), 7.27 (2H, dd, J=4.6, 1.6 Hz), 7.37 (1H, m), 7.71 (1H, br), 8.14 (1H, m), 8.36 (2H, dd, J=4.6, 1.6 Hz), 8.70 (1H, dd, J=4.8, 1.6 Hz), 8.97 (1H, m). IR (KBr) cm-1: 1655, 1620, 1585, 1540.

Reference： [1]Patent: US5246948,1993,A

22
[ 4556-23-4 ]
N-(4-Mesyloxybutyl)-caprylamide [ No CAS ]
4-[4-(caprylamino)butylthio]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94.6%	With sodium hydroxide; sodium methylate In methanol; chloroform; water	8.iii iii) iii) Synthesis of 4-[4-(caprylamino)butylthio]pyridine 4-Mercaptopyridine (415 mg, 3.73 mmol) was dissolved in 30 ml of anhydrous methanol, 4.1 M sodium methylate solution in methanol (0.91 ml, 3.71 mmol) was added and the mixture was stirred for 30 minutes. N-(4-Mesyloxybutyl)-caprylamide 1.00 g, 3.11 mmol) was added and the mixture was refluxed for 3 hours. After cooling, the solvent was distilled off and the residue was dissolved in chloroform. The solution was washed with 1 N aqueous solution of sodium hydroxide and water and dried. The solvent was distilled off. The residue was purified by column chromatography (eluent: ethyl acetate) to obtain the powder which was washed with ether and dried to obtain 990 mg of the desired compound (94.6%, colorless powder), mp: 72.0-73.0° C. Anal. for C19 H32 N2 OS. Calcd. C; 67.81, H; 9.58, N; 8.32. Found: C; 67.70,H; 9.73, N; 8.26. NMR (200 MHz, CDCl3) δ: 0.84 (3H, t, J=7Hz), 1.23 (12H, m), 1.40-1.90 (6H, m), 2.12 (2H, t, J=7Hz), 2.97 (2H, t, J=7Hz), 3.27 (2H, q, J=7Hz), 5.48 (1H, m), 7.07 (2H, dd, J=5, 2Hz), 8.35 (2H, dd, J=5, 2Hz). IR (KBr)cm-1: 3290, 3100, 1630, 1570.

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US5246948, 1993, A

23
[ 4556-23-4 ]
N-(6-Methanesulfonyloxyhexyl)caprylamide [ No CAS ]
4-[6-(caprylamino)hexylthio]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87.4%	With sodium hydroxide; sodium methylate In methanol; chloroform; water	10.iii iii) iii) Synthesis of 4-[6-(caprylamino)hexylthio]pyridine 4-Mercaptopyridine (381 mg, 3.43 mmol) was dissolved in 30 ml of anhydrous methanol and 4.1 M sodium methylate solution in methanol (0.84 ml, 3.43 mmol) was added thereto. The mixture was stirred for 30 minutes. N-(6-Methanesulfonyloxyhexyl)caprylamide (1.00 g, 2.86 mmol) was added and refluxed for 3 hours. After cooling, the solvent was distilled off, the residue was dissolved in chloroform. The solution was washed with 1 N aqueous solution of sodium hydroxide and water and dried. The solvent was distilled off. The residue was purified by column chromatography (eluent: ethyl acetate) to obtain the powder which was washed with ether, and dried to obtain 870 mg of the desired compound (87.4%, colorless powder), mp: 72.0-73.0° C. Anal. for C21 H36 N2 OS. Calcd.: C; 69.18, H; 9.95, N; 7.68. Found: C; 69.14, H; 10.13, N; 7.61. NMR (200 MHz, CDCl3) δ: 0.88 (3H, t, J=7Hz), 1 26 (12H, m), 1.00-2.00 (10H, m), 2.15 (2H, t, J=7Hz), 2.97 (2H, t, J=7Hz), 3.25 (2H, q, J=7Hz), 5.48 (1H, m), 7.10 (2H, dd, J=5, 2Hz), 8.38 (2H, dd, J=5, 2Hz). IR (KBr)cm-1: 3290, 3100, 2920, 2850, 1630, 1570.

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US5246948, 1993, A

24
[ 4556-23-4 ]
[ 155967-70-7 ]
4-[cis-(1,2,3,6-tetrahydrophthalimido)methylthio]pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With triethylamine In ethanol	96.iii iii) iii) Synthesis of 4-[cis-(1,2,3,6-tetrahydrophthalimido)methylthio]pyridine To a suspension of 110 mg (1.0 mmol) of 4-mercaptopyridine and 0.14 ml (1.2 mmol) of triethylamine in 5 ml of ethanol, 2.93 mg (1.2 ml) of cis-(N-bromomethyl)-1,2,3,6-tetrahydrophthalimide was added under ice-cooling with stirring. The mixture was stirred at room temperature for 16 hours. The solvent was distilled off and then the residue was purified by column chromatography (eluent: ethyl acetate) to obtain 250 mg of the desired compound (yield: 91.0%, yellow oil). NMR (200 MHz, CDCl3) δ:2.17-2.27 (2 H, m), 2.53-2.64 (2 H, m), 3.11 (2 H, m), 4.93 (2 H, m), 5.80 (2 H, m), 7.34 (2 H, dd, J=1.2, 4.2 Hz), 8.44 (2 H, bd, J=4.2 Hz). IR (neat)cm-1: 3040, 2950, 1710, 1570.

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US5246948, 1993, A

25
[ 4556-23-4 ]
[ 111992-61-1 ]
[ 6674-22-2 ]
[ 155966-84-0 ]

Yield	Reaction Conditions	Operation in experiment
71.6%	In N-methyl-acetamide; water;	EXAMPLE 145 Synthesis of 4-(2,2-dimethyl-3-phthalimidopropylthio)pyridine To a solution of 0.56 g (5.0 mmol) of 4-mercaptopyridine and 1.48 g (5.0 mmol) of <strong>[111992-61-1](N-3-bromo-2,2-dimethylpropyl)phthalimide</strong> in 20 ml of dimethylformamide, 0.75 ml (5.0 mmol) of 1,8-diazabicyclo[5.4.0]-7-undecene was added, and the mixture was stirred at 80 C. for 8 hours. Water was added, and the mixture was extracted with ethyl acetate. The extract was dried and the solvent was distilled off. The residue was purified by column chromatography (eluent: ethyl acetate) to give 12.0 g of the desired compound (71.6% yield, colorless columns). NMR (200 MHz, CDCl3) delta: 1.13 (6H, s), 3.03 (2H, s), 3.70 (2H, s), 7.17 (2H, dd, J=1.6, 4.6 Hz), 7.72-7.92 (4H, m), 8.38 (2H, dd, J=1.6, 4.6 Hz). IR (KBr) cm-1: 3030, 2960, 1715, 1580, 800, 720.

Reference： [1]Patent: US5246948,1993,A

26
[ 4556-23-4 ]
[ 1316275-31-6 ]
[ 7783-06-4 ]
[ 7787-70-4 ]
3,4-Dihydro-2,6-dimethyl-4-oxo-5-(4-pyridylthio)-quinazoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.7 g (48% theory)	With NaH; In methanol; N,N-dimethyl acetamide; mineral oil;	Preparation of Compound (9) (Compound 8A)--3,4-Dihydro-2,6-dimethyl-4-oxo-5-(4-pyridylthio)-quinazoline To a solution of 3.2 g 4-mercaptopyridine (28.8 mmol) in ml of anhydrous N,N-Dimethylacetamide at 0 C. was added 1.24 g (28.8 mmol) NaH (60% dispersion in mineral oil), and the mix was stirred for 1 hr. To this reaction mixture was added 3.1 g <strong>[1316275-31-6]bromoquinazoline</strong> (6) (0.012 mol), 1.4 g copper (I) bromide, and 0.70 g of copper (I) oxide. The mix was heated at 90 C. for 4 hrs. The reaction mixture was evaporated to dryness, 50 ml of an H2 S/methanol solution (10 g/l) was added to the residue, and the mixture was stirred for 1 hr. The mixture was filtered, and the filtrate was evaporated to dryness. The solid was purified via flash chromatography on silica gel using MeOH/CH2 Cl2 (5:95) to yield 1.7 g (48% theory) of a tan solid: M.P. 235-238 C.; IR (KBr) 3430, 1670, 1633, 1575, 1460, 1408, 1300, 841, 820, 714 cm-1; 1 H NMR (DMSO-d6) delta2.28 (s, 3H), 2.40 (s, 3H), 6.80 (d, 2H, J=5.9 Hz), 7.60 (d, 1H, J=8.3 Hz), 7.80 (d, 1H, J=8.5 Hz), 8.24 (d, 2H, J=6.5 Hz), 12.10 (bs, 1H). Anal. Calcd. for C15 H13 N3 OS.H2 O: C, 59.80; H, 4.98; N, 13.95; S, 10.63. Found: C, 59.58; H, 4.90; N, 13.89; S, 10.62. HRMS Calcd. for C15 H13 N3 OS: 283.0773. Found: 283.0779.

Reference： [1]Patent: US5430148,1995,A

27
[ 4556-23-4 ]
[ 838-85-7 ]
[ 2524-64-3 ]
[ 37968-97-1 ]

Yield	Reaction Conditions	Operation in experiment
85%	With 2-(Dimethylamino)pyridine; sodium iodide; triethylamine In <i>N</i>-methyl-acetamide; dichloromethane	B.10 EXAMPLE B-12 (diphenyl phosphate) EXAMPLE B-12 (diphenyl phosphate) R1 =1-(tertbutyldimethylsilyloxy)ethyl, R2 =methyl, OR6 =OPO(OPh)2 →SHet, R7 =p-methoxybenzyl, Het=4-pyridyl. To a solution of diol (a) (4.28 g; 9.0 millimoles) and dimethylaminopyridine (550 mg; 0.3 equivalents) in dimethylformamide stirring at -70° C. is dropwise added a solution of triethylamine (2.1 ml; 1.1 equivalents) and diphenyl chlorophosphate (3.1 ml) in dichloromethane (10 ml) over 15 minutes. The mixture is stirred for 1 hour to give a solution of diphenyl phosphate (a). This product (a) is treated with 4-mercaptopyridine (1.2 equivalents), triethylamine (1.1 equivalents), sodium iodide (1.2 equivalents) and dimethylformamide (30 ml) at room temperature for 2 hours as in Example F-6 to give the corresponding 4-pyridyl sulfide (b) (4.4 g) in 85% yield.
85%	With 2-(Dimethylamino)pyridine; sodium iodide; triethylamine In <i>N</i>-methyl-acetamide; dichloromethane	F.6 EXAMPLE F-6 EXAMPLE F-6 R1 =1-(tert-butyldimethylsilyloxy)ethyl, R2 =methyl, OR6 =OH→OPO(OPh)2 →SHet, R7 =p-methoxybenzyl, Het=4-pyridyl. Diol (a) (4.28 g; 9.0 millimoles) is treated with dimethylaminopyridine (550 mg; 0.3 equivalents), triethylamine (2.1 ml; 1.1 equivalents), and diphenyl chlorophosphate (3.1 ml) in dimethylformamide and dichloromethane (10 ml) at -70° C. for about 1 hour as in Example B-12 to give a solution of starting diphenyl phosphate (a). To this solution of ester (a) are added 4-mercaptopyridine (1.2 equivalents), triethylamine (1.1 equivalents), sodium iodide (1.2 equivalents) and dimethylformamide. The mixture is warmed to room temperature, stirred for 2 hours, and poured into aqueous sodium hydrogen carbonate-ethyl acetate. The organic layer is separated, washed with water, dried, and concentrated in vacuum. The residue is purified by chromatography over silica gel (Lober B, ethyl acetate) to give 4-pyridyl sulfide (b) (4.4 g). Yield: 85%.
71.6%	With dmap; chloro-trimethyl-silane; triethylamine In dichloromethane; acetonitrile	B.10 EXAMPLE B-10 (chloro) EXAMPLE B-10 (chloro) R1 =1-(triethylsilyloxy)ethyl, R2 =methyl, OR6 =Cl→SHet, R7 =p-methoxybenzyl, Het=4-pyridyl. To a solution of alcohol (a) (800 mg; 1.68 millimoles) in dichloromethane (10 ml) at -60° C. with stirring are dropwise added 4-(dimethylamino)pyridine (40 mg; 0.2 equivalents), triethylamine (0.28 ml; 1.2 equivalents), and diphenyl chlorophosphate (0.42 ml; 1.2 equivalents). After 30 minutes' stirring, the mixture is treated with trimethylsilyl chloride (0.75 ml; 3.9 equivalents) and stirred for 1 hour to give a chloride of (a, R6 =H). This chloride (a) is treated with 4-mercaptopyridine (280 mg; 1.5 equivalents) and triethylamine (0.35 ml; 1.5 equivalents) in acetonitrile (10 ml) for 1 hour at -20° C. as in Example F-4 to give 4-pyridyl sulfide (b) (680 mg). Yield: 71.6%.

33.7%	With 2-(Dimethylamino)pyridine; sodium iodide; triethylamine In <i>N</i>-methyl-acetamide; dichloromethane	B.10 EXAMPLE B-11 (diphenyl phosphate) EXAMPLE B-11 (diphenyl phosphate) R1 =1-hydroxyethyl, R2 =methyl, OR6 =OPO(OPh)2 →SHet, R7 =p-methoxybenzyl, Het=4-pyridyl. To a solution of diol (a) 5.42 g (15.0 millimoles) and dimethylaminopyridine (550 mg; 0.3 equivalents) in dichloromethane (20 ml) stirring at -70° C. is dropwise added a solution of triethylamine (2.1 ml; 1.1 equivalents) and diphenyl chlorophosphate (3.1 ml) in dichloromethane (10 ml) over 15 minutes. The mixture is stirred for 1 hour to give a solution of diphenyl phosphate (a). This product (a) is treated with 4-mercaptopyridine (2.00 g; 1.2 equivalents), triethylamine (2.1 ml; 1.1 equivalents), sodium iodide (2.7 g; 1.2 equivalents), and dimethylformamide (30 ml) at room temperature for 2 hours as in Example F-5 to give 4-pyridyl sulfide (b) (2.30 g). Yield: 33.7%. IR (CHCl3)ν: 3370-3130br, 1766, 1708, 1614, 1580 cm-1.
33.7%	With 2-(Dimethylamino)pyridine; sodium iodide; triethylamine In <i>N</i>-methyl-acetamide; dichloromethane	F.5 EXAMPLE F-5 EXAMPLE F-5 R1 =1-hydroxyethyl, R2 =methyl, OR6 =OH→OPO(OPh)2 →SHet, R7 =p-methoxybenzyl, Het=4-pyridyl. Diol (a) (5.42 g; 15.0 millimoles) in dichloromethane (30 ml) is treated with dimethylaminopyridine (550 mg; 0.3 equivalents), diphenyl chlorophosphate (3.1 ml), and triethylamine (2.1 ml; 1.1 equivalents) for 75 minutes at -70° C. as in Example B-11 to give a solution of starting diphenyl phosphate (a). This solution is mixed with 4-mercaptopyridine (2.00 g; 1.2 equivalents), triethylamine (2.1 ml; 1.1 equivalents), sodium iodide (2.7 g; 1.2 equivalents), and dimethylformamide (30 ml), warmed up to room temperature, and stirred for 2 hours. The mixture is poured onto aqueous sodium hydrogen carbonate-ethyl acetate. The organic layer is separated, washed with water, dried, and concentrated in vacuum. The residue is chromatographed over Lober B eluding with ethyl acetate to give 4-pyridyl sulfide (b) (2.30 g). Yield: 33.7%. IR (CHCl3)ν: 3370-3130br, 1766, 1708, 1614, 1580 cm-1. NMR (VXR-200, CDCl3)δ: 1.18 (3H, d, J=7.2 Hz), 1.32 (3H, d, J=6.4 Hz), 1.76 (>1H, brs), 3.25 (1H, dd, J=6.5 Hz), J=3.0 Hz), 3.30-3.39 (1H, m), 3.48 (1H, ABq, J=14.4 Hz), 3.80 (3H, s), 4.13 (1H, dd, J=10.2 Hz, J=3 Hz), 4.22 (1H, t-type, J=6.3 Hz), 4.94 (1H, ABq, J=14.4 Hz), 5.22, 5.28 (2H, d, J=11.8 Hz), 6.88, 7.39 (4H, A2 B2 q, J=8.8 Hz), 7.06, 8.31 (4H, dA2 B2 q, J=4.6 J=1.6 Hz) ppm.

Reference： [1]Current Patent Assignee: SHIONOGI & CO., LTD. - US4960879, 1990, A
[2]Current Patent Assignee: SHIONOGI & CO., LTD. - US4960879, 1990, A
[3]Current Patent Assignee: SHIONOGI & CO., LTD. - US4960879, 1990, A
[4]Current Patent Assignee: SHIONOGI & CO., LTD. - US4960879, 1990, A
[5]Current Patent Assignee: SHIONOGI & CO., LTD. - US4960879, 1990, A

28
[ 4556-23-4 ]
7β-phenylacetamido-3-chloromethyl-3-cephem-4-carboxylic acid p-methoxybenzyl ester [ No CAS ]
p-methoxybenzyl 7β-phenylacetamido-3-(4-pyridyl)thiomethyl-3-cephem-4-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93.4%	With sodium bicarbonate In ethyl acetate; N,N-dimethyl-formamide	C.1 Preparation C-1 STR17 To a stirred and ice cold solution of 7β-phenylacetamido-3-chloromethyl-3-cephem-4-carboxylic acid p-methoxybenzyl ester (1) (4.87 g; 10 mMol.) and 4-mercaptopyridine (1.45 g; 1.3 Eq.) in N,N-dimethylformamide (15 ml) is added sodium hydrogen carbonate (1.09 g; 1.3 Eq.), and the mixture is stirred at room temperature for 1 hour. The reaction mixture is diluted with ice water and separating solidis collected by filtration, dissolved in ethyl acetate, washed with water, dried, and concentrated under reduced pressure. The residue is washed with ether to give p-methoxybenzyl 7β-phenylacetamido-3-(4-pyridyl)thiomethyl-3-cephem-4-carboxylate (2) (5.25 g). mp. 142°-144° C. Yield: 93.4%.

Reference： [1]Current Patent Assignee: SHIONOGI & CO., LTD. - US5134138, 1992, A

29
[ 4556-23-4 ]
7β-[2-(2-t-butoxycarbonylamino-4-thiazolyl)-2-methoxyiminoacetamido]-3-bromomethyl-3-cephem-4-carboxylic acid diphenylmethyl ester 1β-oxide [ No CAS ]
7β-[2-(2-t-butoxycarbonylamino-4-thiazolyl)-2-methoxyiminoacetamido]-3-(4-pyridyl)thiomethyl-3-cephem-4-carboxylic acid diphenylmethyl ester 1β-oxide [ No CAS ]
[ 66134-95-0 ]

Yield	Reaction Conditions	Operation in experiment
86%	With sodium methylate In N,N-dimethyl-formamide	C.4 Preparation C-4 STR20 To a solution of 4-mercaptopyridine sodium salt prepared from 4-mercaptopyridine (135 mg; 1.3 Eq.) and sodium methoxide in N,N-dimethylformamide (5 ml) is added to a solution of 7β-[2-(2-t-butoxycarbonylamino-4-thiazolyl)-2-methoxyiminoacetamido]-3-bromomethyl-3-cephem-4-carboxylic acid diphenylmethyl ester 1β-oxide (1) (710 mg; 0.94 mMol.) in N,N-dimethylformamide (5 ml), and the mixture is stirred at -30° C. for 30 minutes. The reaction mixture is diluted with ethyl acetate, washed with water, dried, and concentrated in vacuum. The residue is purified by silica gel chromato-graphy (ethyl acetate) to give 7β-[2-(2-t-butoxycarbonylamino-4-thiazolyl)-2-methoxyiminoacetamido]-3-(4-pyridyl)thiomethyl-3-cephem-4-carboxylic acid diphenylmethyl ester 1β-oxide (2) (640 mg). Yield: 86%.

Reference： [1]Current Patent Assignee: SHIONOGI & CO., LTD. - US5134138, 1992, A

30
[ 4556-23-4 ]
7β-[2-(2-t-butoxycarbonylamino-4-thiazolyl)-2-methoxyiminoacetamido]-3-chloromethyl-3-cephem-4-carboxylic acid p-methoxybenzyl ester [ No CAS ]
7β-[2-(2-t-butoxycarbonylamino-4-thiazolyl)-2-methoxyiminoacetamido]-3-(4-pyridyl)thiomethyl-3-cephem-4-carboxylic acid p-methoxybenzyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With sodium methylate In methanol; N,N-dimethyl-formamide	C.3.2 Preparation C-3 2) To a solution of 4-mercaptopyridine (222 mg; 2 Eq.) in N,N-dimethylformamide (10 ml) keeping at 0° C. is added a solution of sodium methoxide in methanol (1.5 Eq.). To this mixture is added 7β-[2-(2-t-butoxycarbonylamino-4-thiazolyl)-2-methoxyiminoacetamido]-3-chloromethyl-3-cephem-4-carboxylic acid p-methoxybenzyl ester (2) (652 mg; 1 mMol.), and the mixture is stirred for 10 minutes. The reaction mixture is diluted with ethyl acetate, washed with water, dried, and concentrated under reduced pressure. The residue is purified by silica gel chromatography (toluene:ethyl acetate) to give 7β-[2-(2-t-butoxycarbonylamino-4-thiazolyl)-2-methoxyiminoacetamido]-3-(4-pyridyl)thiomethyl-3-cephem-4-carboxylic acid p-methoxybenzyl ester (3) (708 mg). Yield: 97%.

Reference： [1]Current Patent Assignee: SHIONOGI & CO., LTD. - US5134138, 1992, A

31
[ 4556-23-4 ]
6-(2-bromoacetamido)-2,2-dimethyl-3-(5-tetrazolyl)penam [ No CAS ]
6-(2-[4-pyridylthio]acetamido)-2,2-dimethyl-3-(5-tetrazolyl)penam [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With triethylamine In dichloromethane	6-(2-[4-Pyridylthio]acetamido)-2,2-dimethyl-3-(5-tetrazolyl)penam 6-(2-[4-Pyridylthio]acetamido)-2,2-dimethyl-3-(5-tetrazolyl)penam To a stirred suspension of 1.0 g (0.0028 mole) of 6-(2-bromoacetamido)-2,2-dimethyl-3-(5-tetrazolyl)penam in 25 ml of methylene chloride is added 0.28 g (0.0028 mole) of triethylamine. The mixture is stirred at ambient temperature until a clear solution is obtained, and then 0.39 g of 4-mercaptopyridine is added. Stirring is continued for a further 4 hours at ambient temperature, and then the solid which has precipitated is filtered off. It is washed with methylene chloride, followed by ether, to give 0.68 g (78% yield) of 6(2-[4-pyridylthio]acetamido)-2,2-dimethyl-3-(5-tetrazolyl)penam, m.p. 120° C. (dec.). The infrared spectrum of the product (KBr disc) shows absorption bands at 1790 cm-1 (β-lactam), 1670 cm-1 (amide II). The NMR spectrum (DMSO-d6) shows absorption bands at 9.0-7.0 ppm (multiplet, pyridine hydrogens), 5.9-5.5 ppm (multiplet, C-5 and C-6 hydrogen), 4.0 ppm (singlet, methylene hydrogens), 1.7 ppm (singlet, C-2 methyl hydrogens) and 1.1 (singlet, C-2 methyl hydrogens).
78%	With triethylamine In dichloromethane	6-(2-[4-Pyridylthio]acetamido)-2,2-dimethyl-3-(5-tetrazolyl)penam 6-(2-[4-Pyridylthio]acetamido)-2,2-dimethyl-3-(5-tetrazolyl)penam To a stirred suspension of 1.0 g (0.0028 mole) of 6-(2-bromoacetamido)-2,2-dimethyl-3-(5-tetrazolyl)penam in 25 ml of methylene chloride is added 0.28 g (0.0028 mole) of triethylamine. The mixture is stirred at ambient temperature until a clear solution is obtained, and then 0.39 g of 4-mercaptopyridine is added. Stirring is continued for a further 4 hours at ambient temperature, and then the solid which has precipitated is filtered off. It is washed with methylene chloride, followed by ether, to give 0.68 g (78% yield) of 6(2-[4-pyridylthio]acetamido)-2,2-dimethyl-3-(5-tetrazolyl)penam, m.p. 120° C. (dec.). The infrared spectrum of the product (KBr disc) shows absorption bands at 1790 cm-1 (β-lactam), 1670 cm-1 (amide II). The NMR spectrum (DMSO-d6) shows absorption bands at 9.0-7.0 ppm (multiplet, pyridine hydrogens), 5.9-5.5 ppm (multiplet, C-5 and C-6 hydrogen), 4.0 ppm (singlet, methylene hydrogens), 1.7 ppm (singlet, C-2 methyl hydrogens) and 1.1 (singlet, C-2 methyl hydrogens).

Reference： [1]Current Patent Assignee: PFIZER INC - US4115385, 1978, A
[2]Current Patent Assignee: PFIZER INC - US4143039, 1979, A

32
[ 4556-23-4 ]
1-[2-(benzyloxy)-4-(4-bromobutoxy)-3-methylphenyl]-3-methylbutan-1-one [ No CAS ]
[ 875455-74-6 ]

Yield	Reaction Conditions	Operation in experiment
83%	With potassium carbonate In acetone at 45℃; for 16h;	136 Potassium carbonate (91 mg, 0.66 mmol) was added to a stirred solution of l-[2-(benzyloxy)-4-(4-bromobutoxy)-3-methylphenyl]-3-methylbutan-l-one (95 mg, 0.22 mmol) and 4-mercaptopyridine (61 mg, 0.55 mmol) in acetone (10 mL) at 45 0C. The reaction mixture was stirred for 16 hr, then the acetone was removed in vacuo. The residue was then mixed with dichloromethane (50 mL) and water (50 mL). The organic layer was separated, dried over MgSO4 and then concentrated in vacuo to give a residue that was purified via column chromatography on silica gel (eluting 0-60% ethyl acetate/hexanes) to give 85 mg (83%) of l-{2-(benzyloxy)-3-methyl-4-[4-(pyridin-4-ylthio)butoxy]phenyl}-3-methylbutan-l- one as a colorless oil. 1H NMR (CDCl3, 500MHz), δ 8.41 (d, 2H), 7.50-7.36 (m, 6H), 7.13 (d, 2H), 6.68 (d, IH), 4.83 (s, 2H), 4.08 (t, 2H), 3.09 (t, 2H), 2.83 (d, 2H), 2.20-2.16 (m, 4H), 2.04-1.95 (m, 4H), 0.90 (d, 6H). MS (ESI): 464 (M + H)+.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2006/14918, 2006, A2 Location in patent: Page/Page column 84

33
[ 4556-23-4 ]
[ 134479-04-2 ]

Yield	Reaction Conditions	Operation in experiment
72%	With sodium hypochlorite; sulfuric acid; sodium chloride In water at -15 - 0℃; for 1h; Inert atmosphere;
	Stage #1: pyridine-4-thiol With hydrogenchloride; dihydrogen peroxide In water at 0℃; for 0.5h; Stage #2: With chlorine In water for 1.5h;	13 Description 13: 4-Pyridylsulfonyl chlorideTo a cooled (0° C.) solution of 4-mercaptopyridine (250 mg, 2.25 mmol) in conc. HCl (2 mL) was added 35% H2O2 solution (0.25 mL, 2.57 mmol) with stirring. After 30 min, chlorine gas was passed through the solution for 1.5 h then ice was added and the volume adjusted by addition of water to 10 mL. A portion of this crude mixture was used immediately for the preparation of Example 12.
	Stage #1: pyridine-4-thiol With sulfuric acid; chlorine at -10℃; for 0.75h; Stage #2: With calcium carbonate In chloroform at -10℃;	5 Pyridine-4-sulfonyl chloride Pyridine-4-sulfonyl chloride 4-Mercaptopyridine (available from Sigma-Aldrich; 1.10 g, 1 mmol) was added to H2SO4 (7.5 mL) and the mixture was cooled to about -10° C. Chlorine gas was bubbled through the solution for 45 minutes, and then calcium carbonate (1.0 g) was added slowly. The reaction mixture was added to CHCl3 (20 mL) and the mixture was cooled to -10° C. More calcium carbonate (7.0 g) was added in portions. The organic layer was decanted and the residue was washed with CHCl3 (2*20 mL). The combined organic layers were dried over Na2SO4, filtered, and evaporated under reduced pressure to give crude pyridine-4-sulfonyl chloride which was used directly in the next step without further purification.

	With hydrogenchloride; water; chlorine at 0℃; for 1h;	127.1 (Step 1) Methyl 2,6-Difluoro-4-[(pyridin-4-ylsulfonyl)amino]benzoate Pyridine-4-thiol (16.7 g, 150 mmol) was dissolved in concentrated hydrochloric acid (110 ml) and water (30 ml). After cooling to 0° C., chlorine gas was bubbled for 1 hour. The reaction solution was diluted with ice-water (75 g), and neutralized by gradually adding sodium hydrogen carbonate. After extraction with methylene chloride (150 ml×3) cooled to 5 to 10° C., the organic layers were combined and dried over anhydrous sodium sulfate. Then, the solvent was removed under reduced pressure to obtain the corresponding sulfonyl chloride. In another reaction vessel, methyl 4-amino-2,6-difluorobenzoate (16.9 g, 90.3 mmol) and pyridine (10 ml) were dissolved in methylene chloride (200 ml). After cooling to -10° C., the above-described solution of the sulfonyl chloride in methylene chloride was added thereto, followed by stirring at room temperature for 6 hours. The organic layer was washed with 0.1 N hydrochloric acid (200 ml×2), and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate=2:1 to 1:1) to obtain the title compound (11.2 g, 38% over two steps).
	With sodium hypochlorite; sulfuric acid at -78 - 0℃; for 4h;	19 Synthesis of pyridine-4-sulfonyl chloride (105): To a stirred solution of pyridine-4-thiol 104 (500 mg, 3.96 mmol) in sulfuric acid (5 mL) under argon atmosphere was added 10-15% sodium hypochlorite solution (60 mL) at -78 °C; warmed to 0 °C and stirred for 4 h at 0 °C. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was diluted with ice cold water (40 mL) and extracted with ice cold CH2C12 (2 x 30 mL). The combined organic extracts were dried over sodium sulfate and concentrated in vacuo to obtain the crude compound 105 (200 mg) as yellow oil. TLC: 10% CH3OH/ CH2C12 (Rf. 0.1).
	With hydrogenchloride; sodium hypochlorite In dichloromethane; water at -5℃; for 1h;	1 Step-1: A mixture of 4-mercapto pyridine (1.5 g, 13.51 mmol), conc. HCI (18 mL) and dichloromethane (18 mL) were stirred at -5 °C and 5 % solution of NaOCI (3.33 g, 44.93 mmol) was added drop wise to the reaction mixture. After completion of the addition, the reaction mixture was slowly stirred for 1 h at -5 °C. After completion of the reaction, the reaction mixture was diluted with water and extracted with dichloromethane (3 x 25 mL). The combined organic layer was used for next step without evaporation.
	With sodium hypochlorite; sulfuric acid In water at 0℃; for 4h;

Reference： [1]Location in patent: experimental part Mun, Jiyoung; Jabbar, Adnan Abdul; Devi, Narra Sarojini; Yin, Shaoman; Wang, Yingzhe; Tan, Chalet; Culver, Deborah; Snyder, James P.; Van Meir, Erwin G.; Goodman, Mark M. [Journal of Medicinal Chemistry, 2012, vol. 55, # 15, p. 6738 - 6750]
[2]Current Patent Assignee: MERCK & CO INC - US2009/54440, 2009, A1 Location in patent: Page/Page column 15
[3]Current Patent Assignee: ROCHE HOLDING AG - US2013/150407, 2013, A1 Location in patent: Paragraph 0198
[4]Current Patent Assignee: EISAI CO LTD - US2015/51395, 2015, A1 Location in patent: Paragraph 0838
[5]Current Patent Assignee: ASSEMBLY BIOSCIENCES, INC. - WO2016/168619, 2016, A1 Location in patent: Paragraph 00207
[6]Current Patent Assignee: OXFORD DRUG DESIGN - WO2021/123237, 2021, A1 Location in patent: Page/Page column 206
[7]Bahadori, Maryam; Brykczyńska, Daria; Chatelain, Paul; Moran, Joseph; Muller, Cyprien; Rowley, Christopher N.; Sau, Abhijit [Angewandte Chemie - International Edition, 2021, vol. 60, # 48, p. 25307 - 25312][Angew. Chem., 2021, vol. 133, # 48, p. 25511 - 25516]

34
[ 4556-23-4 ]
[ 5122-82-7 ]
[ 1185752-26-4 ]

Yield	Reaction Conditions	Operation in experiment
86%	With triethylamine In acetonitrile at 20℃;
86%	With triethylamine In acetonitrile at 20℃;	27 To a solution of adamantan-1-yl bromomethyl ketone (514 mg, 2.0 mmol) in acetonitrile (10 mL) was added pyridine-4-thiol (244 mg, 2.2 mmol), followed by triethylamine (1 mL). The mixture was stirred at ambient temperature overnight, partitioned between ethyl acetate and saturated sodium carbonate. The organic phase was washed with brine, dried over MgSO4 and concentrated in vacuo to give the crude product. Purification with flash column (hexane-ethyl acetate; gradient elution) yielded the title compound as white solid (494 mg, 86 %). mp 114-115 °C; TLC single spot at Rf 0.32 (25 % EtOAc/DCM); 1H NMR (270 MHz, CDCl3) δ 1.70-1.82 (6H, m, 3 x CH2), 1.90 (6H, d, J = 2.8 Hz, 3 x CH2), 2.08 (3H, broad, 3 x CH), 4.01 (2H, s, CH2), 7.08 (2H, dd, J = 4.7, 1.8 Hz, ArH) and 8.38 (2H, dd, J= 4.7, 1.8 Hz, ArH); LC/MS (ESI) m/z 288 (M+H-H); tr = 1.12 min in 5 % water-methanol; HRMS (ESI) calcd. for C17H22NOS (M+H-H) 288.1422, found 288.1420; HPLC tr = 2.64 min (>99 %) in 10% water-acetonitrile.

Reference： [1]Location in patent: experimental part Su, Xiangdong; Pradaux-Caggiano, Fabienne; Vicker, Nigel; Thomas, Mark P.; Halem, Heather; Culler, Michael D.; Potter, Barry V.L. [ChemMedChem, 2011, vol. 6, # 9, p. 1616 - 1629]
[2]Current Patent Assignee: IPSEN SA - WO2009/106817, 2009, A2 Location in patent: Page/Page column 74

35
[ 4556-23-4 ]
[ 138500-85-3 ]
[ 950201-42-0 ]

Yield	Reaction Conditions	Operation in experiment
92%	Stage #1: pyridine-4-thiol With potassium carbonate In N,N-dimethyl-formamide for 0.2h; Stage #2: 4-bromomethylphenylboronic acid pinacol ester In N,N-dimethyl-formamide for 2h;	A.9 To a solution of 4-pyridine thiol (149 mg, 1.35 mmol) in dimethyformamide (5 ml) was added K2CO3 (186 mg, 1.35 mmol) ; the resulting solution was stirred for 12 min and to this subsequently was added a solution of 2-(4-bromomethyl-phenyl)-4,4,5,5- tetramethyl-[l,3,2]dioxaborolane (400 mg, 1.35 mmol) and the resulting solution was stirred for 2 hours. The mixture was then diluted by the addition of water (30 ml) and extracted with AcOEt (3 x 15 ml) ; the organic layer was subsequently dried over Na2SO4 and concentrated in vacuo to yield the crude product. The crude reaction mixture was subsequently purified by Biotage purification (eluting with DCM) to yield intermediate compound 9. (406.0 mg, 1.24 mmol, 92 %).

Reference： [1]Current Patent Assignee: ADDEX THERAPEUTICS SA; JOHNSON & JOHNSON INC - WO2007/104783, 2007, A2 Location in patent: Page/Page column 42

36
[ 4556-23-4 ]
[ 4530-18-1 ]
S-pyridin-4-yl 2-((tert-butoxycarbonyl)amino)-3-phenylpropanethioate [ No CAS ]

Reference： [1]Organic Letters,2010,vol. 12,p. 4716 - 4719

37
[ 4556-23-4 ]
[ 117997-81-6 ]
C₂₂H₂₆N₂O₅S [ No CAS ]

Reference： [1]Organic Letters,2010,vol. 12,p. 4716 - 4719

38
[ 4556-23-4 ]
[ 52071-65-5 ]
(2S)-tert-butyl 2-((1-oxo-3-phenyl-1-(pyridin-4-ylthio)propan-2-yl)carbamoyl)pyrrolidine-1-carboxylate [ No CAS ]

Reference： [1]Organic Letters,2010,vol. 12,p. 4716 - 4719

39
[ 4556-23-4 ]
[ 5241-64-5 ]
S-pyridin-4-yl 2-((tert-butoxycarbonyl)amino)-3-(1H-indol-3-yl)propanethioate [ No CAS ]

Reference： [1]Organic Letters,2010,vol. 12,p. 4716 - 4719

40
[ 4556-23-4 ]
2-amino-5-bromo-6-methyl-3H-quinazolin-4-one hydrochloride [ No CAS ]
[ 2645-22-9 ]
3,4-dihydro-2-amino-6-methyl-4-oxo-5-(4-pyridylthio)quinazoline [ No CAS ]

Reference： [1]Organic Process Research and Development,2010,vol. 14,p. 346 - 350

41
[ 4556-23-4 ]
[ 470-17-7 ]
[ 1245719-01-0 ]

Reference： [1]Chemistry and biodiversity,2010,vol. 7,p. 1681 - 1697

42
[ 4556-23-4 ]
[ 546-43-0 ]
[ 1245719-02-1 ]

Reference： [1]Chemistry and biodiversity,2010,vol. 7,p. 1681 - 1697

43
[ 4556-23-4 ]
[ 536-74-3 ]
[ 1372796-33-2 ]

Yield	Reaction Conditions	Operation in experiment
84%	With indium(III) triflate In toluene for 1h; Reflux;
53%	With palladium diacetate; copper(II) bis(trifluoromethanesulfonate) In 5,5-dimethyl-1,3-cyclohexadiene at 120℃; for 4h; Inert atmosphere;	Typical procedure for the preparation of 2-((1-phenylvinyl)thio)pyridine (3a) General procedure: A test tube was charged with pyridine-2-thiol (0.2 mmol), Pd(OAc)2 (0.004 mmol), Cu(OTf)2 (0.01 mmol), phenylacetylene (0.24 mmol), in xylene (1 mL). The reaction tube was evacuated and back-filled with N2 (3 times, balloon). Then the reaction mixture was stirred at 120°C (oil bath temperature) under N2 balloon for 4 h. After cooling to room temperature, the solvent was extracted with ethyl acetate and washed with brine. After the solvent was evaporated in vacuo, the residues were purified by column chromatography, eluting with petroleum ether/EtOAc to afford pure 2-((1-phenylvinyl)thio)pyridine.

Reference： [1]Sarma, Rupam; Rajesh, Nimmakuri; Prajapati, Dipak [Chemical Communications, 2012, vol. 48, # 33, p. 4014 - 4016]
[2]Ma, Haojie; Ren, Xiaoyu; Zhou, Xiaoqiang; Ma, Chaowei; He, Yongqin; Huang, Guosheng [Tetrahedron Letters, 2015, vol. 56, # 44, p. 6022 - 6029]

44
[ 4556-23-4 ]
[ 766-97-2 ]
[ 1372796-34-3 ]

Yield	Reaction Conditions	Operation in experiment
86%	With indium(III) triflate In toluene for 2h; Reflux;
55%	With palladium diacetate; copper(II) bis(trifluoromethanesulfonate) In 5,5-dimethyl-1,3-cyclohexadiene at 120℃; for 4h; Inert atmosphere;	Typical procedure for the preparation of 2-((1-phenylvinyl)thio)pyridine (3a) General procedure: A test tube was charged with pyridine-2-thiol (0.2 mmol), Pd(OAc)2 (0.004 mmol), Cu(OTf)2 (0.01 mmol), phenylacetylene (0.24 mmol), in xylene (1 mL). The reaction tube was evacuated and back-filled with N2 (3 times, balloon). Then the reaction mixture was stirred at 120°C (oil bath temperature) under N2 balloon for 4 h. After cooling to room temperature, the solvent was extracted with ethyl acetate and washed with brine. After the solvent was evaporated in vacuo, the residues were purified by column chromatography, eluting with petroleum ether/EtOAc to afford pure 2-((1-phenylvinyl)thio)pyridine.

Reference： [1]Sarma, Rupam; Rajesh, Nimmakuri; Prajapati, Dipak [Chemical Communications, 2012, vol. 48, # 33, p. 4014 - 4016]
[2]Ma, Haojie; Ren, Xiaoyu; Zhou, Xiaoqiang; Ma, Chaowei; He, Yongqin; Huang, Guosheng [Tetrahedron Letters, 2015, vol. 56, # 44, p. 6022 - 6029]

45
[ 4556-23-4 ]
[ 20781-20-8 ]
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Yield	Reaction Conditions	Operation in experiment
65%	Stage #1: pyridine-4-thiol With trichloroisocyanuric acid; benzyltrimethylammonium chloride In methanol; dichloromethane at -70℃; for 1.06667h; Stage #2: 2,4-Dimethoxybenzylamine With triethylamine at -70 - 20℃; for 4.16667h;	14.a Reference Example 14N-[4-(1-butylcyclopropyl)benzyl]pyridin-4-ylsulfonamide14-(a): N-(2,4-dimethoxybenzyl)-S-(pyridin-4-yl)thiohydroxylamineTo 18 ml of a methylene chloride solution containing 2.00 g (10.8 mmol) of benzyltrimethyl ammonium chloride were added 836 mg (3.60 mmol) of trichloroisocyanuric acid and 90 μl of methanol, and the mixture was stirred at room temperature for 30 minutes. This solution was added dropwise to 36 ml of a methylene chloride solution containing 1.00 g (9.00 mmol) of 4-mercaptopyridine at -70° C. over 4 minutes, and the mixture was stirred at the same temperature for 1 hour. Then, 4.75 ml (31.6 mmol) of 2,4-dimethoxybenzylamine was added dropwise to the mixture at -70° C. over 10 minutes, then, 1.25 ml (8.97 mmol) of triethylamine was added to the same, and the temperature of the mixture was raised to room temperature over 4 hours. After completion of the reaction, water was added to the reaction mixture under ice-cooling and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was applied to silica gel column chromatography (eluent; n-hexane:ethyl acetate=1:1→0:1 (V/V)), and the fractions containing the objective material were concentrated under reduced pressure to obtain 1.62 g of the title compound as yellowish brown oil. (Yield: 65%)Mass Spectrum (CI, m/z): 277 (M++1).1H-NMR Spectrum (CDCl3, δ ppm): 8.40 (dd, J=4.6, 1.5 Hz, 2H), 7.23 (dd, J=4.6, 1.5 Hz, 2H), 7.14 (d, J=8.2 Hz, 1H), 6.48 (d, J=2.3 Hz, 1H), 6.45 (dd, J=8.2, 2.3 Hz, 1H), 4.03 (d, J=6.1 Hz, 2H), 3.86 (s, 3H), 3.82 (s, 3H), 3.22 (t, J=6.1 Hz, 0.9H).

Reference： [1]Current Patent Assignee: UBE INDUSTRIES LIMITED - US2012/259123, 2012, A1 Location in patent: Page/Page column 97

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Reference： [1]Inorganic Chemistry,2014,vol. 53,p. 1699 - 1711

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Reference： [1]Inorganic Chemistry,2014,vol. 53,p. 1699 - 1711

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5,10,15,20-tetrakis[2,3,5,6-tetrafluoro-4-(4-pyridylsulfanyl)phenyl]porphyrin [ No CAS ]