Name: 1758-46-9|2-Phenoxyethylamine|98%
Brand: Ambeed
SKU: A262607
Price: 8.0 USD
Availability: InStock
Rating: 96 (30 reviews)

1
[ 621-88-5 ]
[ 1758-46-9 ]

Yield	Reaction Conditions	Operation in experiment
88%	With dimethylsulfide borane complex In tetrahydrofuran at 90℃; for 16h; Inert atmosphere;
59%	With dimethylsulfide borane complex In diethylene glycol dimethyl ether at 90℃; for 18h;
	With lithium aluminium tetrahydride; diethyl ether

Multi-step reaction with 2 steps 1: 1 h / 300 °C 2: hydrogen / ethanol / 1 h / 90 °C / 52505.3 Torr

Reference： [1]Valhondo, Margarita; Marco, Isabel; Martín-Fontecha, Mar; Vázquez-Villa, Henar; Ramos, José A.; Berkels, Reinhard; Lauterbach, Thomas; Benhamú, Bellinda; López-Rodríguez, María L. [Journal of Medicinal Chemistry, 2013, vol. 56, # 20, p. 7851 - 7861]
[2]Brasili, Livio; Sorbi, Claudia; Franchini, Silvia; Manicardi, Massimo; Angeli, Piero; Marucci, Gabriella; Leonardi, Amedeo; Poggesi, Elena [Journal of Medicinal Chemistry, 2003, vol. 46, # 8, p. 1504 - 1511]
[3]Uffer; Schlittler [Helvetica Chimica Acta, 1948, vol. 31, p. 1397,1399]
[4]Current Patent Assignee: CHINA PETROCHEMICAL CORPORATION - CN104557610, 2018, B

2
[ 98-59-9 ]
[ 1758-46-9 ]
[ 37075-71-1 ]

Yield	Reaction Conditions	Operation in experiment
92%	With 1-hydroxybenzotriazole supported on polymer In dichloromethane at 60℃;
	With alkali
	With triethylamine In dichloromethane at 0 - 20℃; for 1h; Inert atmosphere;

Reference： [1]Aldrich-Wright, Janice R.; Dankers, Christian; Gordon, Christopher P.; Jurisinec, Ashley; Menti-Platten, Maria; Tadros, Joseph [Chemistry - An Asian Journal, 2022, vol. 17, # 5]
[2]Current Patent Assignee: Marckwald; Chain - DE120047, 1800, C [Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 6, p. 1158][Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 6, p. 1158]
[3]Hajiloo Shayegan, Mojtaba; Li, Zhong-Yuan; Cui, Xin [Chemistry - A European Journal, 2022, vol. 28, # 1]

3
[ 3449-48-7 ]
[ 1758-46-9 ]
[ 121594-01-2 ]

Reference： [1]Pharmaceutical Chemistry Journal,1989,vol. 23,p. 231 - 234
Khimiko-Farmatsevticheskii Zhurnal,1989,vol. 23,p. 299 - 302

4
[ 3598-14-9 ]
[ 1758-46-9 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen; In ethanol; at 90℃; under 52505.3 Torr; for 1h;	(4) In a 1L hydrogenation tank, 100g of <strong>[3598-14-9]phenoxyacetonitrile</strong> and 3g of Raney-Ni, 400mL of ethanol are added and H2 is continuously charged, so that the pressure of the system during the reaction is always maintained at 7MPa. After the reaction was performed at a reaction temperature of 90C for 1 hour, the temperature was lowered. After the temperature in the reactor was lowered to room temperature, the mixture was purged, and phenoxyethylamine (purity of 99% or more) was obtained by filtration and recrystallization. The yield was 93% by weight.

Reference： [1]Collection of Czechoslovak Chemical Communications,1968,vol. 33,p. 1880 - 1894
[2]Journal of the American Chemical Society,1987,vol. 109,p. 4036 - 4046
[3]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 4689 - 4693
[4]Patent: CN104557610,2018,B .Location in patent: Paragraph 0272; 0279

5
[ 83725-61-5 ]
[ 1758-46-9 ]

Yield	Reaction Conditions	Operation in experiment
91%	With hydrazine hydrate In ethanol at 76℃; for 3h;
90%	With hydrazine hydrate In ethanol at 50℃; for 4h;	General procedure: To a solution of 5a,b (3mmol) in ethanol (30mL) was added 85% hydrazine hydrate (0.19mL, 3.3mmol) at 50°C. The reaction mixture was stirred at the same temperature for 4h, cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure to give crude 6a,b (90%).
60%	With hydrazine hydrate; acetic acid In methanol for 4h; Reflux;

39.5 g	With hydrazine hydrate In methanol for 2h; Heating;
	With hydrazine hydrate In ethanol for 4h; Reflux;	4.4. General procedures for the preparation of 4a-4g General procedure: An solution of 3a-3g (11 mmol) and hydrazine hydrate(80%) (9 mL, 142 mmol) in ethanol (60 mL) was refluxed for 4 h, and then cooled to room temperature. The mixture was filtered and the solid was washed with 95% EtOH. The whole filtrate was concentrated and the solid was dissolved in CH2Cl2. The mixture was dried over MgSO4, filtered and concentrated to give the crude product, which was used in the next step without further purification.
	With hydrazine hydrate In ethanol at 50℃; for 4h;
	With hydrazine hydrate In ethanol at 50℃; for 4h;

Reference： [1]Location in patent: experimental part Harjani, Jitendra R.; Liang, Chen; Jessop, Philip G. [Journal of Organic Chemistry, 2011, vol. 76, # 6, p. 1683 - 1691]
[2]Wang, Minghua; Ye, Cheng; Liu, Mingliang; Wu, Zhaoyang; Li, Linhu; Wang, Chunlan; Liu, Xiujun; Guo, Huiyuan [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 14, p. 2782 - 2787]
[3]Location in patent: experimental part Carocci, Alessia; Catalano, Alessia; Lovece, Angelo; Lentini, Giovanni; Duranti, Andrea; Lucini, Valeria; Pannacci, Marilou; Scaglione, Francesco; Franchini, Carlo [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 17, p. 6496 - 6511]
[4]Effland; Helsley; Tegeler [Journal of Heterocyclic Chemistry, 1982, vol. 19, # 3, p. 537 - 539]
[5]Location in patent: experimental part Shan, Wen-Jun; Huang, Ling; Zhou, Qi; Meng, Fan-Chao; Li, Xing-Shu [European Journal of Medicinal Chemistry, 2011, vol. 46, # 12, p. 5885 - 5893]
[6]Wu, Zhaoyang; Lu, Yu; Li, Linhu; Zhao, Rui; Wang, Bin; Lv, Kai; Liu, Mingliang; You, Xuefu [ACS Medicinal Chemistry Letters, 2016, vol. 7, # 12, p. 1130 - 1133]
[7]Chen, Min; Geng, Chun-Wen; Han, Ling; Liu, Yu; Yu, Yong-Kai; Lu, Ai-Min; Yang, Chun-Long; Li, Guo-Hua [New Journal of Chemistry, 2021, vol. 45, # 12, p. 5621 - 5630]

6
[ 146-77-0 ]
[ 1758-46-9 ]
[ 135482-59-6 ]

Yield	Reaction Conditions	Operation in experiment
40%	With N-ethyl-N,N-diisopropylamine In i-Amyl alcohol at 140℃; for 48h;

Reference： [1]Francis, John E.; Webb, Randy L.; Ghai, Geetha R.; Hutchison, Alan J.; Moskal, Michael A.; et al. [Journal of Medicinal Chemistry, 1991, vol. 34, # 8, p. 2570 - 2579]

7
[ 3987-53-9 ]
[ 1758-46-9 ]
[ 98123-71-8 ]

Yield	Reaction Conditions	Operation in experiment
	In chloroform;	EXAMPLE X8 1-(2-Phenoxyethyl)-4-benzyl-2,6-piperazinedione 2-Phenoxyethylamine (1.37 g) and <strong>[3987-53-9]N-benzyliminodiacetic acid</strong> (2.23 g) were mixed and heated to 225, and maintained at this temperature for 15 min. After cooling, chloroform was added and the product purified by column chromatography (SiO2 /CHCl3) to give the title compound as a reddish oil (2.1 g).

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 2058 - 2062
[2]Patent: US4661489,1987,A

8
[ 6547-53-1 ]
[ 1758-46-9 ]
[ 1518-48-5 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1965,vol. 84,p. 521 - 539

9
[ 70659-90-4 ]
[ 1758-46-9 ]

Yield	Reaction Conditions	Operation in experiment
98%	With hydrogenchloride; indium In tetrahydrofuran at 20℃; for 3h;
96%	With ammonium chloride; zinc In ethanol; water for 0.166667h; Heating;
67%	With triphenylphosphine In tetrahydrofuran at 20℃;

Reference： [1]Lee, Jung Gyu; Choi, Kyung Il; Koh, Hun Yeong; Kim, Youseung; Kang, Yonghan; Cho, Yong Seo [Synthesis, 2001, # 1, p. 81 - 84]
[2]Lin, Wenqing; Zhang, Xiaomei; He, Ze; Jin, Yi; Gong, Liuzhu; Mi, Aiqiao [Synthetic Communications, 2002, vol. 32, # 21, p. 3279 - 3284]
[3]Chao, María N.; Li, Catherine; Storey, Melissa; Falcone, Bruno N.; Szajnman, Sergio H.; Bonesi, Sergio M.; Docampo, Roberto; Moreno, Silvia N. J.; Rodriguez, Juan B. [ChemMedChem, 2016, vol. 11, # 24, p. 2690 - 2702]

10
[ 106-95-6 ]
[ 1758-46-9 ]
[ 148870-57-9 ]
3-{3-[allyl-(2-phenoxy-ethyl)-amino]-propyl}-7,8-dimethoxy-1,3-dihydro-benzo[d]azepin-2-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2001,vol. 11,p. 2351 - 2354

11
[ 1758-46-9 ]
[ 148870-57-9 ]
[ 374538-44-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2001,vol. 11,p. 2351 - 2354

12
[ 1758-46-9 ]
[ 221077-37-8 ]
2-{4-[(S)-2-(3-Methoxycarbonyl-propionylamino)-2-(2-phenoxy-ethylcarbamoyl)-ethyl]-phenoxy}-malonic acid diethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane at 20℃; for 18h;
	With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In dichloromethane at 0 - 20℃; for 18h;	48 GENERAL PREPARATION OF A-5 To a mixture of A-4 (1 eq.) in CH2Cl2 (0.2 M) at 0 C. is added EDC (1 eq.) followed by the requisite amine. The reaction is warmed to room temperature and stirred for 18 h. The mixture is diluted with EtOAc and washed with 1 M HCl, sat NaHCO3, and sat. NaCl. The organic phase is dried (MgSO4) and concentrated under reduced pressure.

Reference： [1]Larsen, Scott D.; Barf, Tjeerd; Liljebris, Charlotta; May, Paul D.; Ogg, Derek; O'Sullivan, Theresa J.; Palazuk, Barbara J.; Schostarez, Heinrich J.; Stevens, F. Craig; Bleasdale, John E. [Journal of Medicinal Chemistry, 2002, vol. 45, # 3, p. 598 - 622]
[2]Current Patent Assignee: SWEDISH ORPHAN BIOVITRUM AB - US6353023, 2002, B1 Location in patent: Page column 30,31

13
[ 5503-32-2 ]
[ 1758-46-9 ]
(1,4-dioxaspiro[4,5]dec-2-ylmethyl)(2-phenoxyethyl)amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
15%	With potassium iodide In 2-methoxy-ethanol Heating;
	With potassium iodide In 2-methoxy-ethanol at 160℃; for 0.5h; Microwave irradiation;	4.6. General procedure for the synthesis of the ammines 8-15 General procedure: A 10mL microwave vial was charged with 4 or 5 or 6 (1.0 mmol), a small excess (1.2 mmol) of 2-phenoxy- or (2-methoxyphenoxy)-or (2,6-dimethoxyphenoxy)-ethanamine and a catalytic amount ofpotassium iodide in 1 mL of 2-methoxyethanol. The reaction wasstirred under microwave irradiation at 160 °C (pressure 100 PSI, power 50 W) for 30 min. Then the solvent was evaporated under reduced pressure. The residue was taken up with EtOAc, basified with 5% NaOH. The organic layer was dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The residue was purified by flash column chromatography.

Reference： [1]Brasili, Livio; Sorbi, Claudia; Franchini, Silvia; Manicardi, Massimo; Angeli, Piero; Marucci, Gabriella; Leonardi, Amedeo; Poggesi, Elena [Journal of Medicinal Chemistry, 2003, vol. 46, # 8, p. 1504 - 1511]
[2]Franchini, Silvia; Manasieva, Leda Ivanova; Sorbi, Claudia; Battisti, Umberto M.; Fossa, Paola; Cichero, Elena; Denora, Nunzio; Iacobazzi, Rosa Maria; Cilia, Antonio; Pirona, Lorenza; Ronsisvalle, Simone; Aricò, Giuseppina; Brasili, Livio [European Journal of Medicinal Chemistry, 2017, vol. 125, p. 435 - 452]

14
[ 36236-72-3 ]
[ 1758-46-9 ]
trans-(2-phenoxyethyl)(2-phenyl[1,3]dioxolan-4-ylmethyl)amine [ No CAS ]
cis-(2-phenoxyethyl)(2-phenyl[1,3]dioxolan-4-ylmethyl)amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 35% 2: 15%	With potassium iodide In 2-methoxy-ethanol Heating;

Reference： [1]Brasili, Livio; Sorbi, Claudia; Franchini, Silvia; Manicardi, Massimo; Angeli, Piero; Marucci, Gabriella; Leonardi, Amedeo; Poggesi, Elena [Journal of Medicinal Chemistry, 2003, vol. 46, # 8, p. 1504 - 1511]

15
[ 1758-46-9 ]
[ 207557-35-5 ]
(S)-1-[2-(2-Phenoxy-ethylamino)-acetyl]-pyrrolidine-2-carbonitrile [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 2774 - 2789

16
[ 132684-59-4 ]
[ 1758-46-9 ]
[ 345347-68-4 ]
5-(4-formyl-3,5-dimethoxyphenoxy)valeric aldehyde linker on a polyethylene glycol resin [ No CAS ]
2-butyl-N⁴-hydroxy-N¹-[1-(2-phenoxy-ethylcarbamoyl)-3-phenyl-propyl]-succinamide [ No CAS ]

Reference： [1]Antimicrobial Agents and Chemotherapy,2004,vol. 48,p. 250 - 261

17
[ 24424-99-5 ]
[ 1758-46-9 ]
[ 921596-28-3 ]

Reference： [1]Angewandte Chemie - International Edition,2006,vol. 45,p. 7462 - 7465

18
2-chloro-6-(5-methyl-1H-pyrazol-3-ylamino)-4-phenylnicotinonitrile [ No CAS ]
[ 1758-46-9 ]
2-(2-phenoxyethylamino)-6-(5-methyl-1H-pyrazol-3-ylamino)-4-phenylnicotinonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate In dimethyl sulfoxide at 100℃; for 27h;	1 [Example 1] Compound B (300 mg, 972 µmol), 2-phenoxyethylamine (254 µl) and sodium hydrogencarbonate (817 mg) were added to DMSO (10 ml), and the mixture was stirred at 100°C for 27 hr. After stirring, the reaction mixture was added to cold water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and concentrated, and the residue was washed by suspending in ethyl acetate to give the object compound of 2-(2-phenoxyethylamino)-6-(5-methyl-1H-pyrazol-3-ylamino)-4-phenylnicotinonitrile (130 mg). 1H-NMR (400MHz, DMSO-d6)δ(ppm): 11.87 (1H, br-s), 9.69 (1H, br-s),7.50(5H,m),7.28(2H,t),6.97-6.93(4H.m),6.38(1H,br-s),6.25(1H,br-s),4.18(2H,t),3.82(2H,q),2.06(3H,s).

Reference： [1]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - EP1876178, 2008, A1 Location in patent: Page/Page column 17

19
[ 914086-10-5 ]
[ 1758-46-9 ]
2-(2-phenoxyethylamino)-6-(5-methyl-1H-pyrazol-3-ylamino)-4-methylnicotinonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate In dimethyl sulfoxide at 100℃; for 27h;	2 [Example 2] Compound A (400 mg, 1, 63 mmol), 2-phenoxyethylamine (638 µl) and sodium hydrogencarbonate (1.37 g) were added to DMSO (12 ml), and the mixture was stirred at 100°C for 27 hr. After stirring, the reaction mixture was added to cold water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and concentrated, and the residue was washed by suspending in ethyl acetate to give the object compound of 2-(2-phenoxyethylamino)-6-(5-methyl-1H-pyrazol-3-ylamino)-4-methylnicotinonitrile (66 mg). 1H-NMR(400MHz,DMSO-d6)δ(ppm): 11.84(1H,br-s), 9.48(1H,br-s), 7.27(2H,t), 6.95-6.90(3H,m), 6.79(1H,br-s), 6.31-6.15(2H,m), 4.12(2H,t), 3.75(2H,q), 2.19(3H,s), 2.04(3H,s). m/z=349(M+H)
	With sodium hydrogencarbonate In dimethyl sulfoxide

Reference： [1]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - EP1876178, 2008, A1 Location in patent: Page/Page column 17
[2]Morioka, Masahiko [Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 24, p. 5860 - 5862]

20
2-chloro-6-(5-methyl-1H-pyrazol-3-ylamino)-4-(trifluoromethyl)nicotinonitrile [ No CAS ]
[ 1758-46-9 ]
2-(2-phenoxyethylamino)-6-(5-methyl-1H-pyrazol-3-ylamino)-4-trifluoromethylnicotinonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate In dimethyl sulfoxide at 100℃; for 27h;	3 [Example 3] Compound F (300 mg, 1.00 mmol), 2-phenoxyethylamine (261 µl) and sodium hydrogencarbonate (837 mg) were added to DMSO (10 ml), and the mixture was stirred at 100°C for 27 hr. After stirring, the reaction system was added to cold water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and concentrated, and the residue was washed by suspending in ethyl acetate to give the object compound of 2-(2-phenoxyethylamino)-6-(5-methyl-1H-pyrazol-3-ylamino)-4-trifluoromethylnicotinonitrile (80 mg). 1H-NMR(400MHz,DMSO-d6)δ(ppm): 12.04(1H,br-s), 10.23(1H,br-s), 7.38(1H,br-s), 7.27(2H,t), 6.98-6.91(3H,m), 6.52-6.35(2H,m), 4.15(2H,t), 3. 80 (2H, q), 2.06(3H,s).

Reference： [1]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - EP1876178, 2008, A1 Location in patent: Page/Page column 17

21
[ 914086-12-7 ]
[ 1758-46-9 ]
2-(2-phenoxyethylamino)-6-(5-methyl-1H-pyrazol-3-ylamino)-4-(4-methoxyphenyl)nicotinonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate In dimethyl sulfoxide at 100℃; for 27h;	4 [Example 4] Compound C (300 mg, 885 µmol), 2-phenoxyethylamine (290 µl) and sodium hydrogencarbonate (743 mg) were added to DMSO (10 ml), and the mixture was stirred at 100°C for 27 hr. After stirring, the reaction mixture was added to cold water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and concentrated, and the residue was washed by suspending in ethyl acetate to give the object compound of 2-(2-phenoxyethylamino)-6-(5-methyl-1H-pyrazol-3-ylamino)-4-(4-methoxyphenyl)nicotinonitrile (87 mg). 1H-NMR(400MHz,DMSO-d6)δ(ppm) : 11.87(1H,br-s), 9.63(1H,br-s),7.45(2H,d),7.26(2H,t),7.06(2H,d),6.98-6.91(3H,m),6.88(1H,br-s),6.41(1H,br-s),6.25(1H,br-s),4.17(2H,t),3.82(5H,m),2.05(3H,s).

Reference： [1]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - EP1876178, 2008, A1 Location in patent: Page/Page column 17-18

22
[ 914086-13-8 ]
[ 1758-46-9 ]
2-(2-phenoxyethylamino)-6-(5-methyl-1H-pyrazol-3-ylamino)-4-(pyridin-3-yl)nicotinonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate In dimethyl sulfoxide at 100℃; for 27h;	6 [Example 6] Compound D (150 mg, 483 µmol), 2-phenoxyethylamine (127 µl) and sodium hydrogencarbonate (400 mg) were added to DMSO (3 ml), and the mixture was stirred at 100°C for 27 hr. After stirring, the reaction mixture was added dropwise to cold water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and concentrated, and the residue was washed by suspending in ethyl acetate to give the object compound of 2-(2-phenoxyethylamino)-6-(5-methyl-1H-pyrazol-3-ylamino)-4-(pyridin-3-yl)nicotinonitrile (82 mg). 1H-NMR (400MHz, DMSO-d6) δ (ppm): 12.06 (1H,br-s), 10.22 (1H,br-s), 8.72-8.69(2H,m), 7.98(1H,dd), 7.65(1H,dd), 7.29-7.23(2H,m), 6.96-6.90(3H,m),6.16(1H,br-s),4.23(2H,t),3.67(2H,t),2.22(3H,s). m/z=412 (M+H)

Reference： [1]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - EP1876178, 2008, A1 Location in patent: Page/Page column 18

23
[ 914086-14-9 ]
[ 1758-46-9 ]
2-(2-phenoxyethylamino)-6-(5-methyl-1H-pyrazol-3-ylamino)nicotinonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate In dimethyl sulfoxide at 100℃; for 27h;	14 [Example 14] Compound E (400 mg, 1.72 mmol), 2-phenoxyethylamine (674 µl) and sodium hydrogencarbonate (1.44 g) were added to DMSO (12 ml), and the mixture was stirred at 100°C for 27 hr. After stirring, the reaction mixture was added to cold water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and concentrated, and the residue was washed by suspending in ethyl acetate to give the object compound of 2-(2-phenoxyethylamino)-6-(5-methyl-1H-pyrazol-3-ylamino)nicotinonitrile (85 mg). 1H-NMR (400MHz, DMSO-d6) δ (ppm): 11.86 (1H,s), 9.59 (1H,br-s), 7.50(1H,d), 7.27(2H,t), 6.96-6.90(3H,m), 6.90(1H,br-s), 6.31(1H,br-s), 6.24(1H,br-s), 4.13(2H,t), 3.76(2H,q), 2.04(3H,s).

Reference： [1]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - EP1876178, 2008, A1 Location in patent: Page/Page column 19

24
[ 1000922-87-1 ]
[ 1758-46-9 ]
2-methyl-2-[1-(2-phenoxy-ethylamino)-naphthalene-2-carbonyl]-amino}-propionic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; copper(l) iodide; N,N-diethylsalicylamide In N,N-dimethyl-formamide at 100℃; for 20h;	11.b b) 2-Methyl-2-[1-(2-phenoxy-ethylamino)-naphthalene-2-carbonyl]-amino}-propionic acid3 mg copper(l)iodide, 127 mg potassium phosphate and 105 mg 2-[(1-bromo- naphthalene-2-carbonyl)-amino]-2-methyl-propionic acid methyl ester were placed in a reaction vial, which was evaporated and backfilled with argon three times. A solution of 62 mg 2-phenoxyethylamine and 12 mg N,N-diethylsalicylaminde in 0.5 ml of dry DMF was then added via septum. Under inert conditions the reaction mixture was heated to 1000C for 20 h. It was then diluted with ethyl acetate and water, the pH was adjusted to neutral, the layers were separated and the aqueous layer was extracted with ethyl acetate twice. The combined organic layers were dried over magnesium sulphate and evaporated. After purification by RP-HPLC 12 mg 2-methyl-2-[1-(2-phenoxy- ethylamino)-naphthalene-2-carbonyl]-amino}-propionic acid were obtained.C23H24N2O4 (392.46), LCMS (ESI): 393.16 (MH+).

Reference： [1]Current Patent Assignee: SANOFI - WO2008/409, 2008, A1 Location in patent: Page/Page column 117

25
[ 621-37-4 ]
[ 1758-46-9 ]
[ 848260-72-0 ]

Yield	Reaction Conditions	Operation in experiment
	With WSC*HCl In dichloromethane
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 4h;	4 N-2-Phenoxyethyl-3-hydroxyphenylacetamide Production Example 4 N-2-Phenoxyethyl-3-hydroxyphenylacetamide 3-Hydroxyphenylacetate (1.5 g, 9.88 mmol) was dissolved in dichloromethane. WSC.HCl (2.82 g, 14.76 mmol) and 2-phenoxyethylamine (1.5 g, 10.95 mmol) were added thereto, and then the resultant mixture was stirred for 4 hours at room temperature. After completion of reaction, water was added to the reaction mixture. The resultant mixture was extracted with chloroform, followed by washing with brine. The resultant mixture was subjected to drying over anhydrous sodium sulfate, concentration under reduced pressure, and purification by chromatography, whereby 2.85 g, a stoichiometric amount, of the target compound was obtained as a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ 3.38 (s, 2H) 3.61 (q, J=5 Hz, 2H) 4.00 (t, J=5 Hz, 2H), 5.97 (br, 1H), 6.72 (m, 4H), 6.96 (t, J=8 Hz, 1H), 7.26 (m, 4H).

Reference： [1]Yamazaki, Yukiyoshi; Abe, Kazutoyo; Toma, Tsutomu; Nishikawa, Masahiro; Ozawa, Hidefumi; Okuda, Ayumu; Araki, Takaaki; Oda, Soichi; Inoue, Keisuke; Shibuya, Kimiyuki; Staels, Bart; Fruchart, Jean-Charles [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 16, p. 4689 - 4693]
[2]Current Patent Assignee: KOWA COMPANY, LTD. - US2005/101636, 2005, A1 Location in patent: Page/Page column 20-21

26
[ 621-54-5 ]
[ 1758-46-9 ]
C₁₇H₁₉NO₃ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 4689 - 4693

27
[ 640724-09-0 ]
[ 1758-46-9 ]
[ 640724-10-3 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In dichloromethane at 0 - 100℃; for 0.5 - 12h;	1 [6-CHLORO-N- (2-METHOXYBENZYL)-N'- (2-PHENOXYETHYL)- [1,] 3, 5] triazine- 2, 4-diamine (3); Procedure 1 [0070] [6-CHLORO-N- (2-METHOXYBENZYL)-N'- (2-PHENOXYETHYL)- [1,] 3, 5] triazine- 2, 4-diamine (3). Procedure 1 : 1.00 eq. of 2 in [CH2C12] is cooled to ODC under nitrogen and Et3N or Hunig's base (3.00 eq. ) is added. To the stirring solution, 1.00 eq. [OF 2-PHENOXY-ETHYLAMINE] is added dropwise. The temperature rises several degrees upon completion of addition ; warming is then allowed to continue until the reaction reaches room temperature. The reaction is allowed to stir at room temperature for 12 hours and then the mixture is partitioned between [CHUCK] and 1.0 N [HC1.] The acid layer is extracted once with [CH2C12] and then the pooled [CH2C12] layers washed several times with H20 and once with brine. The [CH2CI2] extract is dried over [NA2S04,] and the solvent removed under reduced pressure to provide crude 3, which is purified by flash chromatography using 1: 4 ethyl acetate (EtOAc)/hexanes as eluent. [0071] Procedure 2: 1.00 eq. of 2 in CH2C12 is cooled to [OOG] under nitrogen and Et3N or Hunig's base (3.00 eq. ) is added. To the stirring solution, 1.00 eq. of 2- [PHENOXY-ETHYLAMINE] is added dropwise. The temperature rises several degrees upon completion of addition; warming is then allowed to continue until the reaction reaches room temperature. The resulting mixture is heated to [100°C] for 30 minutes, cooled to room temperature, and partitioned between [H20/CH2C12.] The aqueous layer is extracted with [CH2C12] and combined organic extracts were dried over [NA2S04.] The solvent is removed under reduced pressure and the resulting residue is purified by flash chromatography [(1] : 4 EtOAc/hexanes) to yield 3.

Reference： [1]Current Patent Assignee: GILEAD SCIENCES INC - WO2004/820, 2003, A2 Location in patent: Page 19; 20

28
[ 403860-11-7 ]
[ 1758-46-9 ]
[ 403858-51-5 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2,3-dichloro-4H-thieno[3,2-b]pyrrole-5-carboxylic acid; 2-phenoxyethanamine With benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.0166667h; Stage #2: With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 18h;	1 Example #1 2,3-Dichloro-5-[N-(2-phenoxyethyl)carbamoyl]-4H-thieno[3,2-b]pyrrole 5-Carboxy-2,3-dichloro-4H-thieno[3,2-b]pyrrole (Method #9; 47 mg, 0.2 mmol) was dissolved in DCM (10 ml) containing 2-phenoxyethylamine (27 mg, 0.2 mmol), HOBT (27 mg, 0.2 mmol) and DIPEA (70 ml, 0.4 mmol).The mixture was stirred for 1 minute before the addition of EDAC (50 mg, 0.26 mmol).The mixture was stirred at ambient temperature for approximately 18 hours before being washed with water.The organic fraction was concentrated and was purified on a Bond Elut column (eluent 1:1 EtOAc/isohexane) to afford the title compound as an off white solid (32 mg). NMR: 12.4 (1H, br), 8.4 (1H, t), 7.3 (1H, d), 7.1 (1H, s), 6.9 (2H, m), 3.5 (2H, m), 3.0 (2H, t); m/z 353.2.

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - US2003/232875, 2003, A1 Location in patent: Page 20

29
5-(3'-carboxy-4-methoxy-1,1'-biphenyl-3-yl)-1,2,5-thiadiazolidin-3-one 1,1-dioxide [ No CAS ]
[ 1758-46-9 ]
[ 692765-67-6 ]

Yield	Reaction Conditions	Operation in experiment
60%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;	93 EXAMPLE 93; 5-F 4-METHOXY-3'-RN-(2-PHENOXYETHYL) CARBAMOYLL-1 S 1'-BIPHENEL-3-YL 2. 5- thiadiazolidin-3-one 1, 1-DIOXIDE To a stirred solution OF 5- (3'-CARBOXY-4-METHOXY-1, 1'-BIPHEN-3-YL)-1, 2,5-thiadiazolidin-3-one 1, 1-dioxide (Example 43) (0.05 g, 0.14 mmol, 1 eq. ) and DIPEA (24 L, 0.14 mmol, 1 eq. ) in DCM (2mL) added HOBt (19 mg, 0.14 mmol, 1 eq. ), 2-phenoxyethylamine (18 RL, 0.14 mmol, 1 eq. ) and EDCI (31 mg, 0.17 mmol, 1.2 eq. ). The reaction was allowed to stir at ambient temperature overnight and then the solvent was removed under reduced pressure. The residue was taken up in acetonitrile: water (1: 1,3 mL) and purified by reverse phase preparative HPLC to afford the title compound as a colourless solid (0.04 g, 60% yields

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2004/41799, 2004, A1 Location in patent: Page 59

30
[ 437384-55-9 ]
[ 1758-46-9 ]
[ 634925-11-4 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In DMF (N,N-dimethyl-formamide) at 55℃; for 24h;	1.B Part B [1946] 2-chloro-5,6-dimethyl-3-nitro-N-(2-phenoxyethyl)pyridin-4-amine 2,4-Dichloro-5,6-dimethyl-3-nitropyridine (1.00 g), anhydrous N,N-dimethylformamide (5 ml), triethylamine (0.63 ml), and 2-phenoxyethylamine (0.59 ml) were combined and the resulting mixture was heated to 55° C. for 24 hours. Thin layer chromatography (TLC) monitoring of the reaction indicated that it was complete. The solvent was removed under reduced pressure and the remaining oil was dissolved in dichloromethane (DCM) and washed once with water. Following 2 additional extractions with DCM, the organic layers were combined, dried with magnesium sulfate, and the solvent was removed under reduced pressure. The product was passed through a column using 20/80 ethyl acetate/hexane as the eluant. NMR analysis of the resulting yellow solid indicated sufficient purity for use in the next step.

Reference： [1]Current Patent Assignee: 3M CO - US2004/10007, 2004, A1 Location in patent: Page 62

31
[ 149806-06-4 ]
[ 1758-46-9 ]
[ 844495-87-0 ]

Yield	Reaction Conditions	Operation in experiment
100%	Stage #1: 6-bromonicotinaldehyde; 2-phenoxyethanamine In ethanol at 20℃; for 7h; Stage #2: With sodium tetrahydroborate In ethanol for 3h;	73 Intermediate 73: (6-BROMO-PYRIDIN-3-YLMETHYL)- (2-PHENOXV-ETHYL)-AMINE A solution of 2-bromo-pyridine-5-carbaldehyde (500MG, 2. 69MMOL) and 2- (PHENOXY)- ethylamine (594mg, 4.3mmol) in anhydrous ethanol (14ML) was stirred at room temperature for 7 hours. Sodium borohydride (102mg, 2. 7MMOL) was then added to the solution, and the resultant mixture was allowed to stir for a further 3 hours before being quenched with water. The resultant mixture was concentrated, to provide (6-BROMO- pyridin-3-ylmethyl)- (2-phenoxv-ethvl)-amine (quantitative), which was'used without further purification. LCMS (Method B): RT = 1. 79 minutes; 307 & 309 (M+H) +.

Reference： [1]Current Patent Assignee: CHARLES RIVER LABORATORIES INTERNATIONAL INC - WO2005/14588, 2005, A1 Location in patent: Page/Page column 71-72

32
[ 58757-38-3 ]
[ 1758-46-9 ]
[ 802916-70-7 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In tetrahydrofuran at -78℃; for 1h;	84.A A. A suspension of 6-chloronicotinic acid (3.94 g, 25 mmol) and SOC12 (0.74 mL, 37.5 mmol) in toluene (45 mL) was heated at reflux for 4 h, then cooled to room temperature. The solvent was removed in vacuo and the residue was dried in vacuo overnight to form a light brown solid. To this solid was added THF (100 mL) and the mixture was cooled TO-78°C. Triethylamine (10.5 mL, 75 mmol) and 2- phenoxyethylamine (3.27 mL, 25 mmol) were then added. The mixture was stirred at - 78°C for 1 h, after which the reaction mixture was poured into saturated NAHCO3 and extracted with EtOAc. The organinc extract was washed with brine, dried and concentrated to give a light brown solid, which was recrystallized from HEXANE/CH2C12 to provide the amide as a white solid (6.3 g, 91%). 1H NMR (400 MHz, CDC13) : 8 3.88-3. 40 (m, 2H), 4.17 (t, J = 5.28 Hz, 2H), 6.60 (br s, 1H), 6.91 (t, J = 7.92 Hz, 2H), 6.99 (d, J = 7. 48 Hz, 1H), 7.28-7. 32 (m, 2H), 7.41 (d, J = 8.32 Hz, 1H), 8.07 (dd, J = 8. 32,2. 20 Hz, 1H), 8.76 (d, J = 2.2 Hz, 1H). HPLC: Retention time = 3.00 min (Method A).

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2004/106296, 2004, A2 Location in patent: Page 66-67

33
[ 58584-83-1 ]
[ 1758-46-9 ]
[ 600726-61-2 ]

Yield	Reaction Conditions	Operation in experiment
1.78 g	With triethylamine In tetrahydrofuran at -78℃; for 1.5h;
	With triethylamine In tetrahydrofuran at -78℃; for 1.5h;	72.A A. To a suspension of 2, 6-dichloronicotinic acid (960 mg, 5 mmol) in toluene (9 mL) was added SOC12 (547 mL, 7.5 mmol) and 2 drops of DMF. The mixture was heated at 90°C for 2 h, then cooled to room temperature. The solvent was removed in vacuo and the residual yellow oil was dried under high vacuum overnight. The residue was dissolved in anhydrous THF (20 mL) and cooled TO-78°C. Triethylamine (2.1 mL, 15 mmol) and 2-phenoxyethylamine (653 PL, 5 mmol) were added, and the reaction was stirred for 1.5 H, then quenched by pouring into a mixture of saturated NAHC03 and CH2C12. The aqueous layer was extracted with CH2C12. The organic extracts were combined and dried (MGS04), then concentrated to give a yellow oil, which was purified by flash chromatography on silica gel eluting with 35% EtOAc/hexane to give the amide as a white solid (1.78 g, 82%). MS (ES+) m/z (M+H) += 311. 16. 1H NMR (400 MHz, CDC13) : 8 3.87-3. 91 (m, 2H), 4.17 (t, J = 5.21 Hz, 2H), 6.90-7. 04 (m, 4H), 7.26-7. 32 (m, 2H), 7.36 (d, J = 8.05 Hz, 1H), 8.09 (d, J = 8. 05 Hz, 1H). HPLC : Retention time = 2.91 min (Method A).

Reference： [1]Yang, Wu; Ruan, Zheming; Wang, Yufeng; Van Kirk, Katy; Zhengping, Ma.; Arey, Brian J.; Cooper, Christopher B.; Seethala, Ramakrishna; Feyen, Jean H. M.; Dickson Jr., John K. [Journal of Medicinal Chemistry, 2009, vol. 52, # 4, p. 1204 - 1208]
[2]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2004/106296, 2004, A2 Location in patent: Page 59

34
[ 749922-36-9 ]
[ 1758-46-9 ]
[ 847577-61-1 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In dichloromethane at 20℃; for 3.16667h;	46.A Triethylamine (8.93 mL, 64.1 mmol) was added to a solution OF 7-BENZYLOXY-4- chloro-3-nitroquinoline (13.45 g, 42.7 mmol), prepared in Parts A-D of Example 1, in dichloromethane (250 mL). 2-Phenoxyethylamine (6.15 mL, 47.0 mmol) was added dropwise over a period of ten minutes, and the reaction mixture was stirred for three hours at ambient temperature. Distilled water (200 mL) was added to the solution, and the aqueous layer was washed with dichloromethane (2 x 200 mL). The combined organic solutions were dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide a solid. The solid was washed with hexanes, isolated by filtration, and dried under reduced pressure to provide 17.14 g of (7-BENZYLOXY-3-NITROQUINOLIN-4-YL)-(2- phenoxyethyl) amine as a yellow solid.

Reference： [1]Current Patent Assignee: 3M CO - WO2005/20999, 2005, A1 Location in patent: Page/Page column 39; 99-100

35
[ 1758-46-9 ]
[ 17288-35-6 ]
1H-pyrrolo[3,2-b]pyridine-2-carboxylic acid (2-phenoxyethyl)amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In DMF (N,N-dimethyl-formamide); at 20℃; for 20h;	To a solution of 1H PYRROLO [3, 2-b] pyridine-2-carboxylic acid (Preparation 32, 50MG, 0. 31MMOL) in DMF (5ML), was added 2-phenoxyethylamine (44AL, 0. 34MMOL), DIPEA (118muL, 0. 68mmol) and HOBt (42mg, 0. 31MMOL) sequentially. The reaction mixture was stirred for 5min prior to the addition of EDCI (42mg, 0. 22MMOL) in one portion. The resulting mixture was stirred for 20h at rt and partitioned between ethyl acetate (50ML) and water (20mL). The layers were separated and the aqueous phase extracted with ethyl acetate (2 x 30mL). The combined organic fractions were washed with brine (20mL), dried (MGS04), filtered and concentrated in vacuo to give an oil. Trituration with diethyl ether/isohexane and collection by filtration gave, after air-drying, the title compound as a cream coloured solid. aH (D6 DMSO): 3.48 (2H, m), 4.14 (2H, t), 6.94 (3H, m), 7.17 (1H, dd), 7.28 (3H, m), 7.77 (1H, d), 8. 37 (1H, dd), 8. 86 (1H, t); m/z (ES+) = 282 [M+ H] + ; RT = 2. 60MIN.

Reference： [1]Patent: WO2004/104001,2004,A2 .Location in patent: Page 87-88

36
C₁₃H₁₁Cl₂N₃O [ No CAS ]
[ 1758-46-9 ]
[ 802916-52-5 ]

Yield	Reaction Conditions	Operation in experiment
73%	With triethylamine In tetrahydrofuran at -78℃; for 1.5h;	1.D D. To a solution OF POC13 (3.57 mL, 38. 4 mmol) and the Part C compound (566 mg, 1.92 mmol) was added SOC12 (2.80 mL, 38. 4 mmol). The suspension was heated at 110°C overnight and a clear yellow solution formed. Following cooling to room temperature, the volatiles were removed and the yellow residue was dissolved in anhydrous THF (8.5 mL). The solution was cooled TO-78°C, and NEt3 (803 UL, 5.76 mmol) and 2-phenoxyethylamine (251 PL, 1.92 mmol) were added. The reaction mixture was stirred at-78°C for 1.5 h. The solvent was removed in vacuo and the residue was purified by flash chromatography on silica gel eluting with a gradient of 0% to 50% EtOAc/hexane to give the chloropyrimidine as a sticky foam (560 mg, 73%). MS (ES+) m/z (M+H) += 397. 46. 1H NMR (400 MHz, CDC13) : 8 3. 17 (s, 3H), 3. 85-3. 89 (m, 2H), 4.16 (t, J = 5. 28 HZ, 3H), 4.91 (d, J=13. 16HZ, 2H), 6.91-6. 99 (m, 3H), 7.16-7. 36 (m, 7H), 8. 87 (b, 1H). HPLC: Retention time = 3.81 min (Method A).
560 mg	With triethylamine In tetrahydrofuran at -78℃; for 1.5h;

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2004/106296, 2004, A2 Location in patent: Page 36
[2]Yang, Wu; Ruan, Zheming; Wang, Yufeng; Van Kirk, Katy; Zhengping, Ma.; Arey, Brian J.; Cooper, Christopher B.; Seethala, Ramakrishna; Feyen, Jean H. M.; Dickson Jr., John K. [Journal of Medicinal Chemistry, 2009, vol. 52, # 4, p. 1204 - 1208]

37
C₁₅H₁₅ClN₂O₄S [ No CAS ]
[ 1758-46-9 ]
[ 802916-56-9 ]

Yield	Reaction Conditions	Operation in experiment
59%	With oxalyl dichloride In dichloromethane	2.F F. To a suspension of the Part E compound (4.57 g, 13.6 mmol) in CH2C12 (300 mL) was added NEt3 (4 mL, 28. 7 mmol) followed by addition of oxalyl chloride (7.8 mL, 2M in CH2C12,15. 6 mmol) and 5 drops OF DMF (gas evolution). The clear reaction mixture was stirred at room temperature for 30 min, then partitioned between CH2CL2 and water. The organic layer was dried over MGS04, concentrated in vacuo, then purified by flash chromatography on silica gel, eluting with 1: 1 EtOAc/hexane to give the amide (3.63 g, 59%) as a white solid. MS (ES+) m/z (M+H) += 456.39. 1H NMR (400 MHz, CDC13) : 8 2.63 (s, 3H), 3.68 (m, 2H), 3.83 (s, 3H), 3.85 (S, 6H), 3.95 (m, 2H), 5.95 (m, 1H), 6.74 (dd, J = 8.8, 0. 8 Hz, 2H), 6.95 (m, 1H), 6.97 (s, 2H), 7.23-7. 27 (m, 2H), 8. 77 (s, 1H). HPLC: Retention time = 3. 28 min (Method A).

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2004/106296, 2004, A2 Location in patent: Page 40

38
[ 134807-39-9 ]
[ 1758-46-9 ]
[ 249540-91-8 ]

Yield	Reaction Conditions	Operation in experiment
83%	With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 12h;	63.A Step A Step A A mixture of (S)-2-isopropyl-succinic acid 1-benzyl ester (10.1 g, 40.2 mmol, Example 3, Step A), 2-phenoxy-l-ethylamine (6.1 g, 44.2 mmol), HOBT * H2O (7.7 g, 50.2 mmol), EDCI * HCl (9.6 g, 50.2 mmol) and N-methylmorpholine (6.6 mL, 60.0 mmol) in 100 mL of CH2Cl2 was stirred at room temperature for 12 hours. The sample was concentrated, then partitioned between EtOAc and saturated NaHCO3 solution. The organic extract was washed with saturated KH2PO4 and brine solutions, dried (MgSO4), filtered, and concentrated. The resultant brown liquid was chromatographed (MPLC, silica gel, 80% hexanes-20% EtOAc to 50% hexanes-50% EtOAc) to give 12.3 g (83%) of (S)-2-[(2-phenoxy-ethylcarbamoyl)-methyl]-3-methyl-butyric acid benzyl ester as a light yellow liquid. MS (APCI) m/z 370.0 (M+1, 100%).

Reference： [1]Current Patent Assignee: PFIZER INC - EP1082127, 2005, B1 Location in patent: Page/Page column 62

39
[ 488838-94-4 ]
[ 1758-46-9 ]
[ 864264-12-0 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate In toluene at 80 - 110℃; for 4 - 16h;	55 Example 55; 6- (2-Phenoxy-ethylamino)-2, 3,4, 5-tetrahydro-lH-benzo [d] azepine Hydrochloride; Use a method similar to the General Procedure 5-1, using 3- (2, 2,2-trifluoroacetyl)- 6-trifluoromethanesulfonyloxy-2, 3,4, 5-tetrahydro-lH-benzo [dlazepine (100 mg, 0.23 mmol) and phenoxyethylamine (63 mg, 0.4 mmol) to give, after chromatography on silica gel eluting with hexane/EtOAc (85: 15) followed by SCX chromatography, 6- (2-phenoxy- ethylamino)-3- (2, 2,2-trifluoroacetyl)-2, 3,4, 5-tetrahydro-1H-benzo[d]azepine as a yellow oil. MS (ES+) m/z : 379 (M+H) +. Use a method similar to the General Procedure 1-1 to deprotect 6- (2-phenoxy- ethylamino)-3- (2, 2,2-trifluoroacetyl)-2, 3,4, 5-tetrahydro-lH-benzo [d] azepine (75 mg, 0.19 mmol). Purify by SCX chromatography to give the free base of the title compound. Use a method similar to the General Procedure 2-2 to give the title compound as a white solid. MS (ES+) m/z : 283 (M+H) +.; General Procedure 5-1; Dissolve the appropriately substituted 3- (2, 2, 2-trifluoroacetyl)-6-trifluoromethane- sulfonyloxy-2, 3,4, 5-tetrahydro-lH-benzo [d] azepine (1 equiv. ), palladium (II) acetate (0.1- 0.4 equiv. ), BINAP (0.2-0. 8 equiv. ; BINAP/catalyst ratio 2: 1) and cesium carbonate (1.4- 3. 0 equiv. ) in toluene (0.2-0. 05 M solution). Add the amine (1-3 equiv. ), degas the mixture with vacuum/nitrogen or argon purge and heat at 80-110°C for 4-16 h. Cool the mixture to ambient temperature, dilute with EtOAc, filter through a pad of silica gel or through Celitet) washing with EtOAc or ether, and evaporate the solvent to obtain the crude mixture. Alternatively, partition the reaction mixture between brine or saturated aqueous NaHCO3 and EtOAc, ether or DCM, dry the organic layer over Na2S04, and concentrate to obtain the crude mixture. Purify the crude mixture by chromatography on silica gel eluting with hexane/EtOAc mixtures and further SCX chromatography if needed.

Reference： [1]Current Patent Assignee: ELI LILLY & CO - WO2005/82859, 2005, A1 Location in patent: Page/Page column 81; 161-162

40
[ 112559-69-0 ]
[ 1758-46-9 ]
[ 895134-47-1 ]

Yield	Reaction Conditions	Operation in experiment
94%	With thiophene; hydrogen In tetrahydrofuran at 140℃; for 16h;	B.3 A mixture of intermediate compound (prepared ac- cording to teachings in WO99/58530 of which the content is included herein) (0.025 mol) and 2-phenoxyethanamine (0.036 mol) in THF (300 ml) was hydrogenated at 140 °C for 16 hours with Pd/C 10 % (3 g) as a catalyst in the presence of thiophene solution (3ml). After uptake of H2 (1 equivalent), the catalyst was filtered off and the filtrate was evaporated. The residue was triturated in 2-propanol. The precipitate was filtered off and dried. Yielding: 12.4 g of final compound 7 (94 %).

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2006/67139, 2006, A1 Location in patent: Page/Page column 66

41
[ 895136-09-1 ]
[ 1758-46-9 ]
[ 895134-53-9 ]

Yield	Reaction Conditions	Operation in experiment
18%	Stage #1: C₂₀H₂₈N₄O₄S; 2-phenoxyethanamine With tetrabutylammomium bromide; potassium carbonate In acetonitrile at 120℃; for 0.25h; Microwave heating; Stage #2: With polystyrene carboxaldehyde resin In dichloromethane; acetonitrile at 100℃; for 0.333333h; Microwave heating;	B.8.a A mixture of intermediate compound 15 (prepared according to A7.g) (0.000078 mol), 2-phenoxyethanamine (0.000156 mol), N,N,N-tributyl-l-butanaminium bromide (0.000078 mol) and K2CO3 (0.000156 mol) in CH3CN (0.5 ml) was heated in a micro- wave oven for 15 minutes at 120 °C and then resin-linked-CHO (0.000312 mol) and CH2Cl2 (1 ml) were added. The reaction mixture was heated in a microwave oven for 20 minutes at 100 °C and the solids were filtered off. The solvent was evaporated and the residue was purified in a manifold (eluent 1: EtOAc; eluent 2: CH2Cl2/CH3OH 96/4). The product fractions were collected and further purified by Catch in an ISOLUTE SCX-3 cartridge and then released with CH3OHTNH3. Finally, the desired fractions were purified by high-performance liquid chromatography, then the product fractions were collected and the solvent was evaporated. Yield: 0.0066 g of final compound 28 (18 %).

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2006/67139, 2006, A1 Location in patent: Page/Page column 69

42
[ 895136-16-0 ]
[ 1758-46-9 ]
C₂₆H₃₃N₅O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With caesium carbonate In acetonitrile at 150℃; for 0.333333h; Molecular sieve; Microwave heating;	A.10.c A mixture of intermediate compound 22 (prepared according to AlO.b) (0.0055 mol), 2- phenoxyethanamine (0.0110 mol), Cs2CO3 (0.0110 mol) and Molecular Sieves 4 (0.5 g) in CH3CN (40 ml) was heated for 20 minutes at 150 °C under microwave irradiation, then CH2Cl2 was added and the reaction mixture was filtered over celite. The solvent was evaporated and the obtained residue was purified by short open column chromatog- raphy (eluent: CH2Cl2/ (CH3OH/NH3) 97/3). The product fractions were collected and the solvent was evaporated. Yield: 2.330 g of intermediate compound 23 (88 %).

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2006/67139, 2006, A1 Location in patent: Page/Page column 43

43
C₁₁H₁₂BrN₃O₄S [ No CAS ]
[ 1758-46-9 ]
C₁₈H₁₉BrN₄O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With caesium carbonate In acetonitrile at 150℃; for 0.333333h; Microwave heating;	A.12.d A mixture of intermediate compound 39 (0.001518 mol),2-phenoxyethanamine (0.0030 mol) and Cs2CO3 (0.0030 mol) in dry CH3CN (10 ml) was stirred in a microwave oven (Milestone) for 20 minutes at 150 °C, then the cooled reaction mixture was filtered over celite and the filtrate was evaporated. The residue was purified by open column chromatography over silica gel (eluent 1 : CH2Cl2/EtOAc 1/1; eluent 2: CH2C12/CH3OH 96/4). The product fractions were collected and the sol- vent was evaporated. Yield: 0.52 g of intermediate compound 40 (85 %).

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2006/67139, 2006, A1 Location in patent: Page/Page column 47

44
C₁₂H₁₃BrN₂O₄S [ No CAS ]
[ 1758-46-9 ]
C₁₉H₂₀BrN₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With caesium carbonate In acetonitrile at 170℃; for 0.333333h; Molecular sieve; Microwave heating;	A.14.d Reaction in microwave oven. A mixture of intermediate compound 45 (0.0037 mol), 2- phenoxyethanamine (0.0074 mol), Cs2CO3 (0.0074 mol) and 4 A molecular sieves (0.330 g) in CH3CN (25 ml) was heated for 20 minutes at 170 °C. The precipitate was filtered off through dicalite and the filtrate's solvent was evaporated. The residue was purified by short open column chromatography over silica gel (eluent: CH2C12/CH3OH 94/6). The product fractions were collected and the solvent was evaporated. Yield: 1.4 g of intermediate compound 46 (94 %).

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2006/67139, 2006, A1 Location in patent: Page/Page column 49

45
[ 897918-10-4 ]
[ 1758-46-9 ]
2-isopropyl-4-[(2-phenoxyethyl)amino]-5-phenylisothiazol-3(2H)-one 1,1-dioxide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With triethylamine In acetonitrile at 120℃; for 0.0833333h; Microwave irradiation;	8 Example s; 2-Isopropyl-4-[(2-phenoxyethyl)amino]-5-phenyIisothiazol-3(2£f)-one 1,1-dioxide EPO A solution of 4-chloro-2~isopropyl-5-phenylisothiazol-3(2H)-one 1,1-dioxide (0.20Og, OJOOmmol), TEA (0.106g, 1.050mmol) and 2-phenoxyethylamine (0.144g, 1.050mmol) in MeCN (3mL) was heated at in a microwave reactor 120°C for 5 mins. The residue was 5 purified by silica gel column chromatography (Horizons Biotage) using a 65:35 mixture of heptane and EtOAc as eluant to give the title compound (0.262g, 97%); 1H NMR (500 MHz, CDCl3): 87.57-7.54 (m, 2H), 7.49-7.45 (m, 3H), 7.32-7.27 (m, 2H), 7.02-6.97 (m, IH), 6.86- 6.83 (m, 2H), 5.71-5.66 (br m, IH), 4.46-4.39 (m, IH), 3.89 (t 2H), 3.27 (q 2H), 1.60 (d 6H); 13C NMR (125 MHz, CDCl3): δ 158.5, 158.2, 135.6, 131.7, 130.0, 129.8, 129.1, 125.1, 121.8, 10 114.7, 108.0, 65.8, 47.8, 43.6, 20.4; Mass Spectrum: M-H+ 387.

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2006/73366, 2006, A1 Location in patent: Page/Page column 208-209

46
[ 4858-85-9 ]
[ 1758-46-9 ]
[ 313654-73-8 ]

Yield	Reaction Conditions	Operation in experiment
100%	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In acetonitrile; at 180℃; for 0.333333h;microwave irradiation;	A. Preparation of the intermediate compounds; Example Al; a) Preparation of intermediate compound 1; Reaction in microwave oven. A mixture of 2-phenoxyethanamine (0.010 mol), 2,3- <strong>[4858-85-9]dichloropyrazine</strong> (0.012 mol) and l,8-diazabicyclo(5.4.0.)undec-7-ene (DBU) (0.012 mol) in CH3CN (20 ml) was heated for 20 minutes at 180 0C. The solvent was evaporated. The residue was purified by short open column chromatography over silica gel (eluent: CH2Cl2). The product fractions were collected and the solvent was evaporated. Yield: 2.5 g of intermediate compound 1 (quantitative yield; used in next reaction step, without further purification).
2.36 g (49%)	With potassium carbonate; In hexane; ethyl acetate; acetonitrile;	Step 1: 2-Chloro-3-(2-phenoxyethylamino)pyrazine. A mixture of 2-phenoxyethylamine (2.65 g, 19.3 mmol), <strong>[4858-85-9]2,3-<strong>[4858-85-9]dichloropyrazine</strong></strong> (2.88 g, 19.3 mmol) and K2CO3 (2.67 g, 19.3 mmol) in acetonitrile (8 mL) was stirred in a sealed tube for 12 h at room temperature, and for a further 9.5 h at 80 C. The reaction mixture was diluted with ether, filtered, and concentrated. The residue was purified by chromatography on silica gel using n-hexane/EtOAc (7:3) as eluent to give 2.36 g (49%) of the title compound as a yellowish oil that solidified on standing: mp 51-53 C.; HRMS m/z calcd for C12H12ClN30 (M)+249.0669, found 249.0659. Anal. (Cl2H12ClN30) C, H, N.

Reference： [1]Patent: WO2007/71646,2007,A1 .Location in patent: Page/Page column 33
[2]Patent: US6465467,2002,B1

47
[ 1059705-52-0 ]
[ 1758-46-9 ]
C₁₉H₂₄N₄O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
26%	With potassium phosphate In 1,2-dimethoxyethane at 100℃; for 20h;
	With potassium phosphate In 1,2-dimethoxyethane at 110℃; for 22h;	3a.2 An oven-dried vial was subsequently charged with 0.1 eq. of a palladium source [Pd], 0.2 eq. (biph)P(Eu)2, 1.0 eq. 1 -(3-chloro-4-nitro-phenyl)-4-methyl-piperazine and 1.4 eq. base. The vial was evacuated and purged with argon, and the respective amine HNR1R2 (1.3 eq.) was added. The solvent was added to obtain a concentration of 1.0 M of the arylhalide 1-(3-chloro-4-nitro-phenyl)-4-methyl-piperazine. The vial was sealed and heated to 1100C for 22 h.The reaction mixture was transferred into a flask using H2O and MeOH and the total volume was reduced to less than 10 mL Purification was achieved by prep. HPLC. In order to remove any ammonium formate derivative formed during preparative HPLC, the resulting product was taken up in chloroform, extracted twice with saturated aq. NaHCO3, the combined aq. phases were re-extracted with chloroform, and the combined organic phases were dried over MgSO4.

Reference： [1]Tasler, Stefan; Mies, Jan; Lang, Martin [Advanced Synthesis and Catalysis, 2007, vol. 349, # 14-15, p. 2286 - 2300]
[2]Current Patent Assignee: Corporacion Quimico Farmaceutica Esteve SA - WO2006/69807, 2006, A1 Location in patent: Page/Page column 105

48
[ 927693-03-6 ]
[ 1758-46-9 ]
C₂₀H₂₄N₄O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	With potassium phosphate In 1,2-dimethoxyethane at 100℃; for 20h;
	With potassium phosphate In 1,2-dimethoxyethane at 110℃; for 22h;	1a.2 An oven-dried vial was subsequently charged with 0.1 eq. of a palladium source [Pd], 0.2 eq. (biph)P(βu)2, 1.0 eq. arylhalide B with X = -O-Benzyl, -O-Methyl, -CN or - C(=O)-OCH3 and 1.4 eq. base. The vial was evacuated and purged with argon, and the respective amine HNR1R2 (1.3 eq.) was added. The solvent was added to obtain a concentration of 1.0 M of the arylhalide B. The vial was sealed and heated to either 1000C in case of toluene as the solvent or 110°C in case of DME as the solvent in each case for 22 h. EPO The reaction mixture was transferred into a flask using H2O and MeOH and the total volume was reduced to less than 10 mL Purification was achieved by prep. HPLC. In order to remove any ammonium formate derivative formed during preparative HPLC, the resulting product was taken up in chloroform, extracted twice with saturated aq. NaHCO3, the combined aq. phases were re-extracted with chloroform, and the combined organic phases were dried over MgSO4. If any additional workup was applied, this is indicated in the table 1.

Reference： [1]Tasler, Stefan; Mies, Jan; Lang, Martin [Advanced Synthesis and Catalysis, 2007, vol. 349, # 14-15, p. 2286 - 2300]
[2]Current Patent Assignee: Corporacion Quimico Farmaceutica Esteve SA - WO2006/69807, 2006, A1 Location in patent: Page/Page column 98-101

49
4-methyl-2-methylsulfanyl-3,4-dihydro-quinazoline hydroiodide [ No CAS ]
[ 1758-46-9 ]
(4-Methyl-3,4-dihydro-quinazolin-2-yl)-(2-phenoxy-ethyl)-amine hydroiodide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	In acetonitrile at 80℃; screw-capped vial;	11.c c) (4-Methyl-3,4-dihydro-quinazolin-2-yl)-(2-phenoxy-ethyl)-amine hydroiodide 2-Phenoxyethylamine (26 mg, 0.19 mmol) was added to a solution of 4-methyl-2-methylsulfanyl-3,4-dihydro-quinazoline hydroiodide (50 mg, 0.16 mmol) in acetonitrile (1 ml), and the mixture was heated overnight (80° C.) in a screw-capped vial. The solvent was then evaporated and the mixture was suspended in diethyl ether. The title compound (52 mg, 62%) was obtained from this mixture by filtration. MS: m/e=282.1 [M+H+]. 1H NMR (CDCl3): δ 1.40 (3H, d), 3.72 (2H, m), 4.14 (2H, m), 4.80 (2H, q), 6.94-7.07 (3H, m), 7.11-7.16 (2H, m), 7.26-7.34 (4H, m), 7.89 (1H, bs), 8.56 (1H, bs), 10.25 (1H, bs).

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2006/252779, 2006, A1 Location in patent: Page/Page column 10

50
8-Bromo-6-chloro-4-methyl-2-methylsulfanyl-3,4-dihydro-quinazoline hydroiodide [ No CAS ]
[ 1758-46-9 ]
(8-Bromo-6-chloro-4-methyl-3,4-dihydro-quinazolin-2-yl)-(2-phenoxy-ethyl)-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	Stage #1: 8-Bromo-6-chloro-4-methyl-2-methylsulfanyl-3,4-dihydro-quinazoline hydroiodide; 2-phenoxyethanamine In acetonitrile at 200℃; for 0.5h; sealed tube; Stage #2: With sodium hydroxide; dihydrogen peroxide In dichloromethane; water; acetonitrile	25.d d) (8-Bromo-6-chloro-4-methyl-3,4-dihydro-quinazolin-2-yl)-(2-phenoxy-ethyl)-amine 8-Bromo-6-chloro-4-methyl-2-methylsulfanyl-3,4-dihydro-quinazoline hydroiodide (141 mg, 0.33 mmol) and 2-phenoxyethyl amine (53.5 mg, 0.39 mmol) were dissolved in acetonitrile (1 ml) and heated to 200° C. in a sealed tube in a microwave oven for 30 minutes. After cooling the reaction was treated with 1N aqueous sodium hydroxide solution, methylene chloride and 5 to 7 drops of 30% aqueous hydrogen peroxide solution. After the reaction has ceased the layers were separated and the aqueous phase was extracted with methylene chloride. The combined organic layers were dried over sodium sulfate, filtered, the solvent was evaporated and the residue was purified by column chromatography (CH2Cl2:MeOH:aq conc NH3=9:1:0.1) to yield the title compound as an off-white solid (60 mg, 47%). (MS: n/e=394.0, 396.0, 398.1 [M+H+]). 1H NMR (CDCl3): δ 1.22 (3H, d); 3.64 (2H, q), 4.12 (2H, t), 4.47 (2H, q), 6.25 (t, 1H), 6.50 (1H, s) 6.89-7.03 (4H, m), 7.25-7.31 (2H, m), 7.35 (1H, s).

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2006/252779, 2006, A1 Location in patent: Page/Page column 13

51
6-Chloro-4-methyl-2-methylsulfanyl-3,4-dihydro-quinazoline hydroiodide [ No CAS ]
[ 1758-46-9 ]
(6-Chloro-4-methyl-3,4-dihydro-quinazolin-2-yl)-(2-phenoxy-ethyl)-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	Stage #1: 6-Chloro-4-methyl-2-methylsulfanyl-3,4-dihydro-quinazoline hydroiodide; 2-phenoxyethanamine In acetonitrile at 170℃; for 0.5h; sealed tube; Stage #2: With sodium hydroxide; dihydrogen peroxide In dichloromethane; water; acetonitrile	26.d d) (6-Chloro-4-methyl-3,4-dihydro-quinazolin-2-yl)-(2-phenoxy-ethyl)-amine 6-Chloro-4-methyl-2-methylsulfanyl-3,4-dihydro-quinazoline hydroiodide (106 mg, 0.30 mmol) and 2-phenoxyethyl amine (168 mg, 1.2 mmol) were dissolved in acetonitrile (0.9 ml) and heated to 170° C. in a sealed tube in a microwave oven for 30 minutes. After cooling the reaction was treated with 1N aqueous sodium hydroxide solution, methylene chloride and 5 to 7 drops of 30% aqueous hydrogen peroxide solution. After the reaction has ceased the layers were separated and the aqueous phase was extracted with methylene chloride. The combined organic layers were dried over sodium sulfate, filtered, the solvent was evaporated and the residue was purified by column chromatography (CH2Cl2:MeOH:aq conc NH3=9:1:0.1) to yield the title compound as a white solid (88 mg, 93%). (MS: m/e=316.0, 318.0 [M+H+]). 1H NMR (CDCl3): δ 1.23 (3H, d), 3.56 (2H, m), 4.05 (2H, t), 4.47 (1H, q), 5.95 (1H, bs), 6.27 (1H, bs), 6.69 (1H, d), 6.90-7.01 (4H, m), 7.29 (2H, t).

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2006/252779, 2006, A1 Location in patent: Page/Page column 13

52
5,8-Dichloro-4-methyl-2-methylsulfanyl-3,4-dihydro-quinazoline hydroiodide [ No CAS ]
[ 1758-46-9 ]
(5,8-Dichloro-4-methyl-3,4-dihydro-quinazolin-2-yl)-(2-phenoxy-ethyl)-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	Stage #1: 5,8-Dichloro-4-methyl-2-methylsulfanyl-3,4-dihydro-quinazoline hydroiodide; 2-phenoxyethanamine In acetonitrile at 170℃; for 0.5h; sealed tube; Stage #2: With sodium hydroxide; dihydrogen peroxide In water; acetonitrile	28.e e) (5,8-Dichloro-4-methyl-3,4-dihydro-quinazolin-2-yl)-(2-phenoxy-ethyl)-amine 5,8-Dichloro-4-methyl-2-methylsulfanyl-3,4-dihydro-quinazoline hydroiodide (116 mg, 0.30 mmol) and 2-phenoxyethyl amine (126 mg, 0.9 mmol) were dissolved in acetonitrile (0.9 ml) and heated to 170° C. in a sealed tube in a microwave oven for 30 minutes. After cooling the reaction was treated with 1N aqueous sodium hydroxide solution (0.9 ml) and 5 to 7 drops of 30% aqueous hydrogen peroxide solution. The reaction was diluted with water and the product precipitated as a white solid, which was filtered off, washed with water and dried in vacuo to yield the title compound (98 mg, 93%). (MS: m/e=350.2, 352.2 [M+H+]). 1H NMR (d6-DMSO): δ 1.07 (3H, d), 3.57 (2H, q), 4.05 (2H, t), 4.55 (1H, q), 6.39 (1H, t), 6.59 (1H, s), 6.72 (1H, d), 6.86 (1H, t), 6.92 (2H, d), 7.11 (1H, d), 7.22 (2H, t).

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2006/252779, 2006, A1 Location in patent: Page/Page column 14

53
4-Methyl-2-methylsulfanyl-7-trifluoromethyl-3,4-dihydro-quinazoline hydroiodide [ No CAS ]
[ 1758-46-9 ]
(4-Methyl-7-trifluoromethyl-3,4-dihydro-quinazolin-2-yl)-(2-phenoxy-ethyl)-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	Stage #1: 4-Methyl-2-methylsulfanyl-7-trifluoromethyl-3,4-dihydro-quinazoline hydroiodide; 2-phenoxyethanamine In acetonitrile at 170℃; for 0.5h; sealed tube; Stage #2: With sodium hydroxide; dihydrogen peroxide In dichloromethane; water; acetonitrile	68.d d) (4-Methyl-7-trifluoromethyl-3,4-dihydro-quinazolin-2-yl)-(2-phenoxy-ethyl)-amine 4-Methyl-2-methylsulfanyl-7-trifluoromethyl-3,4-dihydro-quinazoline hydroiodide (116 mg, 0.30 mmol) and 2-phenoxyethyl amine (126 mg, 0.9 mmol) were dissolved in acetonitrile (0.9 ml) and heated to 170° C. in a sealed tube in a microwave oven for 30 minutes. After cooling the reaction was treated with 1N aqueous sodium hydroxide solution, methylene chloride and 5 to 7 drops of 30% aqueous hydrogen peroxide solution. After the reaction has ceased the reaction was diluted with little water and the precipitated product was filtered off, washed with water, dried in vacuo to yield the title compound as a white solid (104 mg, 94%). (MS: m/e=350.2, 351.1 [M+H+]). 1H NMR (CDCl3): δ 1.25 (3H, d), 3.58 (2H, m), 4.05 (2H, t), 4.55 (1H, q), 6.08 (1H, bt), 6.37 (1H, s), 6.91-7.01 (5H, m), 7.11 (1H, d), 7.29 (2H, t).

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2006/252779, 2006, A1 Location in patent: Page/Page column 22

54
[ 1758-46-9 ]
[ 51997-51-4 ]
1-[carbazolyl-⁽⁴⁾-oxy]-3-(2-phenoxyethylamino)-propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32%		(a) 1-[carbazolyl-(4)-oxy]-3-(2-phenoxyethylamino)-propan-2-ol yield 32% of theory; m.p. 105-107 C., from 4-(2,3-epoxypropoxy)-carbazole and 2-phenoxyethylamine.

Reference： [1]Patent: US4503067,1985,A

55
[ 869059-55-2 ]
[ 1758-46-9 ]
1-[[4-(1,1-dimethylethyl)phenyl]sulfonyl]-2,3-dihydro-N-(2-phenoxy-ethyl)-(2S)-1H-indole-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	With PS-EDC resin (N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide combined with polystyrene resin) In dichloromethane at 20℃; for 20h;	2 400 mg (equivalent to 0.556 mmol) of PS-EDC resin (N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide combined with polystyrene resin) are conditioned in 4 ml of dichloromethane under agitation for 15 minutes, and then the solvent is eliminated by filtration. The resin is rinsed several times with 4 ml of dichloromethane, and then a solution of 100 mg (0.278 mmol) of acid obtained according to preparation IV and 25.4 mg (0.185 mmol) of 2-phenoxyethanamine in solution in 6 ml of dichloromethane are added. The mixture is agitated for 20 hours at ambient temperature and 0.278 mmol of isocyanate resin are added. The mixture is agitated for 2 hours at ambient temperature and 0.278 mmol of Amberlite IRA 400 resin are added. The mixture is again agitated for 2 hours and then the resins are eliminated by filtration. The filtrate is then concentrated under reduced pressure. In this way the expected compound is obtained in the form of a white powder (yield=58%). NMR 1H (DMSO, 250 MHz) δ: 8.37 (t, 1H, NHCO), 7.70 (d, 2H, Harom.), 7.55 (d, 2H, Harom.), 7.45 (d, 1H, Harom.), 7.32-7.20 (m, 3H, Harom.), 7.10 (d, 1H, Harom.), 7.03-6.93 (m, 4H, Harom.), 4.80 (dd, 1H, NCHCO), 4.02 (t, 2H, CH2OPh), 3.50 (m, 2H, CH2NCO), 3.11 (dd, 1H, CH2CHCO), 2.91 (dd, 1H, CH2CHCO), 1.25 (s, 9H, tBu).

Reference： [1]Current Patent Assignee: INVENTIVA SA - US2007/99960, 2007, A1 Location in patent: Page/Page column 7

56
[ 1810-72-6 ]
[ 1758-46-9 ]
[ 1136478-92-6 ]

Yield	Reaction Conditions	Operation in experiment
73%	at 120℃; for 1h;microwave;	<strong>[1810-72-6]2,6-Dichloroquinoline</strong> (1.0 g, 5.1 mmol) and 2-phenoxyethylamine (1.5 g, 11 mmol) were microwaved at 120 C. for 1 h. The reaction mixture was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 100:0?70:30 gradient). (6-Chloro-quinolin-2-yl)-(2-phenoxy-ethyl)-amine was obtained as a light yellow solid (1.1 g, 73%), MS: m/e=299.3 (M+H+).
73%	at 120℃; for 1h;Irradiation;	Step A: A stirred mixture of <strong>[1810-72-6]2,6-dichloro-quinoline</strong> (1.0 g, 5.1 mmol) and 2-phenoxyethylamine (1.5 g, 11 mmol) was heated in the microwave for 1 h at 120 C. Purification by flash chromatography on silica gel (ethyl acetate/heptane 100:0?70:30) yielded (6-chloro-quinolin-2-yl)-(2-phenoxy-ethyl)-amine as a light yellow oil (1.1 g, 73%), MS: m/e=299.3 (M+H+).

Reference： [1]Patent: US2009/88451,2009,A1 .Location in patent: Page/Page column 14
[2]Patent: US2009/233927,2009,A1 .Location in patent: Page/Page column 8

57
[ 586-42-5 ]
[ 67715-76-8 ]
[ 1758-46-9 ]
[ 1039454-22-2 ]

Reference： [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 3985 - 4001

58
[ 802916-55-8 ]
[ 1758-46-9 ]
[ 802916-56-9 ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: C₁₅H₁₆N₂O₅S With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 1.5h; Stage #2: 2-phenoxyethanamine With triethylamine In dichloromethane for 0.0833333h;

Reference： [1]Yang, Wu; Ruan, Zheming; Wang, Yufeng; Van Kirk, Katy; Zhengping, Ma.; Arey, Brian J.; Cooper, Christopher B.; Seethala, Ramakrishna; Feyen, Jean H. M.; Dickson Jr., John K. [Journal of Medicinal Chemistry, 2009, vol. 52, # 4, p. 1204 - 1208]

59
[ 19156-63-9 ]
[ 32315-10-9 ]
[ 1758-46-9 ]
[ 1084627-83-7 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-amino-5-ethylthiophene-3-carboxylic acid methyl ester; bis(trichloromethyl) carbonate With triethylamine In dichloromethane at 1 - 30℃; for 2h; Stage #2: 2-phenoxyethanamine In dichloromethane at 1 - 30℃; for 1h; Stage #3: With sodium methylate In methanol at 60℃; for 1h;	13 Example 13 6-ethyl-1-[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-3-(2-phenoxyethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione To a solution (40 mL) of methyl 2-amino-5-ethylthiophene-3-carboxylate (0.5 g) in methylene chloride were added triphosgene (0.35 g) and triethylamine (0.98 mL), and the mixture was stirred at room temperature for 2 hr. To the reaction mixture was added 2-phenoxyethanamine (1 g), and the mixture was further stirred at room temperature for 1 hr, and extracted with water and chloroform. The chloroform layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was dissolved in methanol (50 mL), sodium methoxide (28% methanol solution, 1.3 g) was added, and the mixture was stirred at 60°C for 1 hr. The reaction mixture was neutralized with hydrochloric acid (10% methanol solution), and the precipitated solid was collected by filtration. The obtained solid was dissolved in N,N-dimethylformamide (10 mL), 3-[4'-(bromomethyl)biphenyl-2-yl]-5-(trichloromethyl)-1,2,4-oxadiazole (0.38 g) and potassium carbonate (0.12 g) were added, and the mixture was stirred at 50°C for 2 hr. The reaction mixture was diluted with ethyl acetate, washed successively with 5% aqueous potassium hydrogensulfate solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography and dissolved in tetrahydrofuran (5 mL) and methanol (5 mL). 1N Aqueous sodium hydroxide solution (5 mL) was added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was adjusted to pH 4 with water and 1N hydrochloric acid, and the mixture was extracted with ethyl acetate. The obtained ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The precipitated solid was collected by filtration to give the title compound as colorless crystals (0.24 g, 54%). 1H NMR (400 MHz, CDCl3)δ1.27 (3H, t, J = 7.2), 2.76 (2H,d, J = 7.2), 4.25 (2H, t, J = 6.0), 4.48 (2H, t, J = 5.6), 5.17 (2H, s),6.89-6.93 (3H, m), 7.02 (1H, s), 7.22-7.26 (2H, m), 7.32 (2H, d, J = 8.4),7.40-7.54 (4H, m), 7.62 (1H, t, J = 7.6), 7.84 (1H, d, J = 8.0)

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP2151440, 2010, A1 Location in patent: Page/Page column 154-155

60
[ 849585-22-4 ]
[ 1758-46-9 ]
[ 1204186-83-3 ]

Yield	Reaction Conditions	Operation in experiment
77%	In ethyl acetate at -15 - 20℃; for 18h;	2 EXAMPLE 2: Preparation of 2-phenoxyethylamine lactate (compound V)2-Phenoxyethylamine lactate (compound V) is obtained by salification of phenoxyethylamine with lactic acid, according to the following reaction:10 g of phenoxyethylamine (RN 1758-46-9 available commercially from the company Aldrich, ref. 40,726-7) are dissolved in 70 ml of ethyl acetate in a reactor. 6.02 ml of D,L-lactic acid (1 equivalent) are then added and the mixture is stirred at room temperature for 15 hours. The milky medium thus obtained is cooled to -15°C for 2 hours. A precipitate forms. The mixture is maintained for a further 1 hour at -15°C and the precipitate obtained is filtered off on a sinter funnel and rinsed with 5 ml of ethyl acetate. The solid is then dried in a desiccator under vacuum at 500C. A white wax is obtained. Recovered mass: 16.57 g. The reaction yield is 77%.

Reference： [1]Current Patent Assignee: L'OREAL SA - WO2010/4016, 2010, A1 Location in patent: Page/Page column 18 - 19

61
[ 1758-46-9 ]
[ 77-92-9 ]
2-phenoxyethylamine 2-hydroxypropane-1,2,3-tricarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	In ethanol at 20℃; for 15h;	1 EXAMPLE 1 : Preparation of 2-phenoxyethylamine 2-hydroxypropane-1 ,2,3- tricarboxylate (= 2-phenoxyethylamine citrate): compound IV2-Phenoxyethylamine 2-hydroxypropane-1 ,2,3-tricarboxylate (compound IV)is obtained by salification of phenoxyethylamine with citric acid, according to the following reaction: Ethanol Citric acid 15 h room temperature phenoxyethylamineMW = 137 18 MW = 137 18 192 13 C8H11 NO C6H8O7120 g of phenoxyethylamine (RN 1758-46-9 commercially available from the company Aldrich, ref. 40,726-7) are dissolved in 2L of ethanol in a reactor equipped with a mechanical stirrer. 56.04 g of citric acid are then added. A compact precipitate rapidly forms (vigorous stirring required).After stirring for 15 hours, the compact solid is filtered off on a sinter funnel and is then washed with 150 ml of ethanol. The solid obtained is dried in a desiccator under vacuum at 500C. Recovered mass: 145 g. The reaction yield is 82%.Phenoxyethylamine (starting material) may also be prepared according to one of the processes described in the literature and indicated previously in the description (cf. hereinabove).

Reference： [1]Current Patent Assignee: L'OREAL SA - WO2010/4016, 2010, A1 Location in patent: Page/Page column 17 - 18

62
2-methyl-2-((4-(trifluoromethyl)phenyl)sulfonyl)propanoic acid [ No CAS ]
[ 1758-46-9 ]
[ 1315564-64-7 ]

Yield	Reaction Conditions	Operation in experiment
54%	Stage #1: 2-methyl-2-((4-(trifluoromethyl)phenyl)sulfonyl)propanoic acid With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 23℃; for 0.166667h; Darkness; Inert atmosphere; Stage #2: 2-phenoxyethanamine In tetrahydrofuran at 23℃; for 1h; Darkness; Inert atmosphere;
15%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 16h;	C Synthesis of 2-Methyl-N-(2-phenoxy-ethyl)-2-(4-trifluoromethyl-benzenesulfonyl)- propionamide (Example 3, Table 4)To a solution of 80 mg (0.27 mmol) of 2-methyl-2-(4-trifluoromethyl-benzenesulfonyl)- propionic acid in DCM (4 mL) are added N,N-diisopropylethylamine (56 μ, 0.328 mmol), PS-DCC (506 mg, PolymerLabs, loading 1.6 mmol/g) and DMAP (cat.). The reaction is shaken at room temperature on an orbital shaker for 16 h. The resins are separated by filtration and washed with DCM (5 mL). The filtrate is washed with saturated aqueous NaHC03 solution. The organic layer is separated, dried (Na2S04), filtered and the filtrate isconcentrated under reduced pressure. The residue is purified by column chromatography (silica, eluent: DCM, ethyl acetate) to give 17 mg of 2-methyl-N-(2-phenoxy-ethyl)-2-(4- trifluoromethyl-benzenesulfonyl)-propionamide. Yield: 15%; ES-MS: m/z 416 [M+H].

Reference： [1]Seleem, Mohamed A.; Rodrigues De Almeida, Nathalia; Chhonker, Yashpal Singh; Murry, Daryl J.; Guterres, Zaira Da Rosa; Blocker, Amanda M.; Kuwabara, Shiomi; Fisher, Derek J.; Leal, Emilse S.; Martinefski, Manuela R.; Bollini, Mariela; Monge, María Eugenia; Ouellette, Scot P.; Conda-Sheridan, Martin [Journal of Medicinal Chemistry, 2020, vol. 63, # 8, p. 4370 - 4387]
[2]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - WO2011/88015, 2011, A1 Location in patent: Page/Page column 49

63
[ 32315-10-9 ]
[ 1125632-05-4 ]
[ 1758-46-9 ]
[ 1228465-85-7 ]

Yield	Reaction Conditions	Operation in experiment
63%	Stage #1: bis(trichloromethyl) carbonate; N-[5-(3-amino-4-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide With triethylamine In tetrahydrofuran at 0℃; for 0.5h; Stage #2: 2-phenoxyethanamine In tetrahydrofuran at 20℃; for 3h;	32 Example 32Production of N-[5-(4-fluoro-3-[(2-phenoxyethyl)carbamoyl]amino}phenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide To a solution of bis(trichloromethyl) carbonate (30 mg, 0.102 mmol) in tetrahydrofuran (2 mL) was added dropwise a suspension of N-[5-(3-amino-4-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide (100 mg, 0.290 mmol) produced in Example 16(vi) and triethylamine (100 μL, 0.725 mmol) in tetrahydrofuran (2 mL) at 0° C., and the mixture was stirred at 0° C. for 30 min. 2-Phenoxyethanamine (45 μL, 0.348 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature for 3 hr. Ethyl acetate (6 ml) and water (4 mL) were added to the reaction mixture, and the mixture was stirred at room temperature for 30 min. The precipitated solid was collected by filtration to give the title compound (93 mg, 63%) as a white solid.1H-NMR (DMSO-d6, 300 MHz) δ 0.88-1.04 (4H, m), 1.93-2.05 (1H, m), 3.45 (2H, q, J=5.4 Hz), 4.00 (2H, t, J=5.4 Hz), 6.73 (1H, ddd, J=8.8, 3.9, 3.0 Hz), 6.88-7.03 (4H, m), 7.09 (1H, d, J=8.7 Hz), 7.17-7.34 (3H, m), 7.99 (1H, dd, J=7.0, 3.0 Hz), 8.15 (1H, d, J=8.7 Hz), 8.60 (1H, d, J=2.6 Hz), 12.70 (1H, br s).

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US2011/237620, 2011, A1 Location in patent: Page/Page column 46

64
[ 1362456-86-7 ]
[ 1758-46-9 ]
[ 1362456-76-5 ]

Yield	Reaction Conditions	Operation in experiment
67%	With triethylamine In tetrahydrofuran at 20℃; for 1.5h;	12 To a stirred yellow solution of VII (371.8 mg, 1.089 mmol) in anhydrous THF (10 mL) was added 2-phenoxyethylamine (165 mg, 157 μL, 1,1x1.089 mmol) and then, dropwise, triethylamine (121 mg, 168 μL, 1.1x1.089 mmol). The solution was stirred for 1.5 hours at room temperature. The colorless solution was then diluted with CH2Cl2 and washed with 1N HCl, distilled water, and saturated NaCl. The organic layer was dried over anhydrous MgSO4, filtered, and concentrated. The crude product was purified by column chromatography on silica gel using hexanes/ethyl acetate (1:1, v/v) to yield 260.6 mg (67%) of a 11 as a clear light yellow oil: Rf=0.39 (hexanes/ethyl acetate, 1:1, v/v); 1HNMR (CDCl3) δ 7.26 (td, 3J=8.0 Hz, 4J=1.1 Hz, 2H), 6.98 (d, 3J=8.0 Hz, 1H), 6.96 (m, 1H), 6.94 (d, 4J=1.0 Hz, 1H), 6.92 (dd, 3J=8.7 Hz, 1H), 6.86 (d, 3J=8.1 Hz, 2H), 5.21 (bs, 1H, NH), 5.06 (s, 2H), 4.03 (t, 3J=5.0 Hz, 2H), 3.80 (s, 3H), 3.59 (q, 3J=5.2 Hz, 2H, NCH2) and 2.29 (s, 3H). Exact mass (EST) calculated for C19H22NO6 [M+H]=360.1442. found 360.1443.

Reference： [1]Current Patent Assignee: RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY - US2012/59007, 2012, A1 Location in patent: Page/Page column 11

65
[ 1453496-31-5 ]
[ 1758-46-9 ]
[ 1453497-48-7 ]

Yield	Reaction Conditions	Operation in experiment
52%	With silver carbonate In ethanol at 50℃; for 3.5h;	1-114 80 mg (0.30 mmol) of N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroethanethioamide 48 µl (0.36 mmol) of 2-phenyloxyethylamine 73 mg (0.33 mmol) of silver carbonate Ethanol 50°C, 3.5h E 52
52%	With silver carbonate In ethanol at 50℃; for 3.5h;	1-114 80 mg (0.30 mmol) of N-[1-((6-chloropyridin-3 -yl)methyl)pyridin-2(1H) -ylidene]-2,2,2-trifluor oethanethioamide 48 µl (0.36mmol) of 2-phenyloxyethy lamine 73 mg (0.33 mmol) of silver carbonate Ethano 1 50°C, 3.5h E 52

Reference： [1]Current Patent Assignee: MITSUI CHEMICALS,INC. - EP2633756, 2013, A1 Location in patent: Paragraph 0300; 0301
[2]Current Patent Assignee: MEIJI HOLDINGS CO., LTD - EP2634174, 2013, A2 Location in patent: Paragraph 0292

66
[ 1758-46-9 ]
[ 51997-51-4 ]
[ 72956-10-6 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 8626 - 8655

67
[ 921596-28-3 ]
[ 1758-46-9 ]

Yield	Reaction Conditions	Operation in experiment
60.3%	With trifluoroacetic acid; In dichloromethane; at 20℃; for 12h;	To a solution of <strong>[921596-28-3]tert-butyl (2-phenoxyethyl)carbamate</strong> (0.4 g, 1.686 mmol) in DCM (6 mF) was added 2,2,2-trifluoroacetic acid (1 mF, 13.46 mmol) at once. The reaction mixture was stirred at room temperature for 12 h. The solvents were removed in vacuo, water (10 mF) was added to the solid with stirring and pH was adjusted to 8 with sat NaHC03. The mixture was extracted with DCM (20 mF x3), washed with water (50 mF), then organic layer was dried over NaiSOi and concentrated to afford a brown oil. The brown oil was purified by silica gel chromatography eluting with pet. ether :EtOAc(5: 1) to give desired product 2- phenoxyethanamine (150 mg, 1.017 mmol, 60.3 % yield) as yellow solid. FCMS (M+H) = 138, Retention time (0.01% TFA) = 1.04.

Reference： [1]Patent: WO2019/244066,2019,A2 .Location in patent: Page/Page column 237; 293; 294
[2]MedChemComm,2015,vol. 6,p. 239 - 246
[3]Journal of Medicinal Chemistry,2020,vol. 63,p. 4370 - 4387

68
[ 1758-46-9 ]
[ 3598-14-9 ]

Reference： [1]ChemSusChem,2015,vol. 8,p. 92 - 96
[2]Organic and Biomolecular Chemistry,2016,vol. 14,p. 3356 - 3359

69
[ 75-15-0 ]
[ 181308-92-9 ]
[ 1758-46-9 ]
(RS)-4-hydroxy-3-(2-phenoxyethyl)-5,6-bis(4-methoxyphenyl)-3,4-dihydro-2H-1,3-thiazine-2-thione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With triethylamine In acetonitrile at 0℃; for 15h; Inert atmosphere; Schlenk technique;

Reference： [1]Kröger, Denis; Brockmeyer, Fabian; Kahrs, Christoph [Organic and Biomolecular Chemistry, 2015, vol. 13, # 26, p. 7223 - 7229]

70
[ 30562-34-6 ]
[ 1758-46-9 ]
17-(2-phenoxyethylamino)-17-demethoxygeldanamycin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90.6%	In dichloromethane at 20℃;	General Procedure for Preparation of Compounds 2-9 General procedure: To GA (34mg, 0.06 mmol, 1.0 equiv.) in dichloromethane (6 mL) was added phenoxyethylamine (0.60 mmol, 10.0 equiv.). The reaction mixture was stirred overnight at room temperature, and TLC was used to monitor the progress of the reaction. When the reaction completed, the mixture was diluted with dichloromethane (25 mL) and washed with 1.5 N HCl (2 25 mL) followed by brine (3 30 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The residue was purified by flash column chromatography (silica gel, ethyl acetate/petroleumether = 1:1) to afford 3 as purple solid (90.6%). 17-(2-phenoxyethylamino)-17-demethoxygeldanamycin(3). 1H NMR (600 MHz, CDCl3) 9.14 (s, 1H, 1-CONH), 7.34 - 7.28 (m, 3H, 19-H, 5’-H and 7’-H), 7.00 (t, J= 6.8 Hz, 1H, 6’-H), 6.96 (s, 1H, 3-H), 6.93 (d, J = 8.4 Hz,2H, 4’-H and 8’-H), 6.58 (t, J = 11.3 Hz, 1H, 4-H), 5.90 (d, J= 9.1 Hz, 1H, 1-H), 5.86 (t, J = 10.4 Hz, 1H, 9-H), 5.19 (s,1H, 7-H), 4.88 (br s, 2H, 7-CONH2), 4.31 (d, J = 9.7 Hz, 1H,6-H), 4.22 - 4.17 (m, 2H, 2’-H), 4.00 (d, J = 11.7 Hz, 1H,1’-H), 3.90 (d, J = 11.5 Hz, 1H, 1’-H), 3.60 - 3.56 (m, 1H,11-H), 3.48 - 3.43 (m, 1H, 12’-H), 3.36 (s, 3H, 12-OMe),3.27 (s, 3H, 6-OMe), 2.79 - 2.68 (m, 2H, 10’H and 15’-H),2.40 (t, J = 12.2 Hz, 1H, 15’-H), 2.02 (s, 3H, 2-Me), 1.80 (brs, 5H, 8-Me and 13-H), 1.75 - 1.70 (m, 1H, 14-H), 1.00 (d, J= 5.0 Hz, 6H, 10-Me and 14-Me); 13C NMR (150 MHz,CDCl3) 183.9 (18-C), 180.9 (21-C), 168.4 (1-C), 158.0 (3’-C), 156.1 (7-CONH2), 145.0 (17-C), 141.0 (20-C), 135.8 (5-C), 135.0 (2-C), 133.7 (9-C), 132.8 (8-C), 129.7 (5’-C and7’-C), 126.9 (4-C), 126.6 (3-C), 121.7 (6’-C), 114.6 (4’-Cand 8’-C), 109.2 (19-C), 109.0 (16-C), 81.7 (7-C), 81.4 (6-C), 81.2 (12-C), 72.6 (11-C), 65.8 (2’-C), 57.2 (6-OMe),56.8 (12-OMe), 45.1 (1’-C), 35.1 (13-C), 34.5 (15-C), 32.3(10-C), 28.6 (14-C), 23.1 (13-Me), 12.8 (8-Me), 12.7 (2-Me), 12.4 (10-Me); ESI-MS: m/z 688.6 [M + Na]+C36H47N3NaO9 calcd. 688.8.

Reference： [1]Li, Zhenyu; Jia, Lejiao; Xu, Hongjiao; Lu, Chunhua; Shen, Yuemao [Medicinal Chemistry, 2015, vol. 11, # 5, p. 482 - 488]

71
[ 1697446-45-9 ]
[ 1758-46-9 ]
[ 1821240-76-9 ]

Yield	Reaction Conditions	Operation in experiment
	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; sodium t-butanolate; DavePhos In 1,4-dioxane at 80℃; for 8h; Inert atmosphere;

Reference： [1]Veena Vani, Kotla; Ramesh, Garlapati; Venkata Rao, Chunduri [Journal of Heterocyclic Chemistry, 2016, vol. 53, # 5, p. 1528 - 1533]

72
1-oxa-4-thiaspiro[4.5]decan-2-ylmethyl 4-methylbenzenesulfonate [ No CAS ]
[ 1758-46-9 ]
{1-oxa-4-thiaspiro[4.5]decan-2-ylmethyl}(2-phenoxyethyl)amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	With potassium iodide In 2-methoxy-ethanol at 160℃; for 0.5h; Microwave irradiation;	4.6. General procedure for the synthesis of the ammines 8-15 General procedure: A 10mL microwave vial was charged with 4 or 5 or 6 (1.0 mmol), a small excess (1.2 mmol) of 2-phenoxy- or (2-methoxyphenoxy)-or (2,6-dimethoxyphenoxy)-ethanamine and a catalytic amount ofpotassium iodide in 1 mL of 2-methoxyethanol. The reaction wasstirred under microwave irradiation at 160 °C (pressure 100 PSI, power 50 W) for 30 min. Then the solvent was evaporated under reduced pressure. The residue was taken up with EtOAc, basified with 5% NaOH. The organic layer was dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The residue was purified by flash column chromatography.

Reference： [1]Franchini, Silvia; Manasieva, Leda Ivanova; Sorbi, Claudia; Battisti, Umberto M.; Fossa, Paola; Cichero, Elena; Denora, Nunzio; Iacobazzi, Rosa Maria; Cilia, Antonio; Pirona, Lorenza; Ronsisvalle, Simone; Aricò, Giuseppina; Brasili, Livio [European Journal of Medicinal Chemistry, 2017, vol. 125, p. 435 - 452]

73
2-(chloromethyl)-1,4-dithiaspiro[4.5]decane [ No CAS ]
[ 1758-46-9 ]
{1,4-dithiaspiro[4.5]decan-2-ylmethyl}(2-phenoxyethyl)amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
15%	With potassium iodide In 2-methoxy-ethanol at 160℃; for 0.5h; Microwave irradiation;	4.6. General procedure for the synthesis of the ammines 8-15 General procedure: A 10mL microwave vial was charged with 4 or 5 or 6 (1.0 mmol), a small excess (1.2 mmol) of 2-phenoxy- or (2-methoxyphenoxy)-or (2,6-dimethoxyphenoxy)-ethanamine and a catalytic amount ofpotassium iodide in 1 mL of 2-methoxyethanol. The reaction wasstirred under microwave irradiation at 160 °C (pressure 100 PSI, power 50 W) for 30 min. Then the solvent was evaporated under reduced pressure. The residue was taken up with EtOAc, basified with 5% NaOH. The organic layer was dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The residue was purified by flash column chromatography.

Reference： [1]Franchini, Silvia; Manasieva, Leda Ivanova; Sorbi, Claudia; Battisti, Umberto M.; Fossa, Paola; Cichero, Elena; Denora, Nunzio; Iacobazzi, Rosa Maria; Cilia, Antonio; Pirona, Lorenza; Ronsisvalle, Simone; Aricò, Giuseppina; Brasili, Livio [European Journal of Medicinal Chemistry, 2017, vol. 125, p. 435 - 452]

74
[ 1624255-71-5 ]
[ 1758-46-9 ]
1,3-dimethyl-8-(2-phenoxyethyl)-6,7,8,9-tetrahydropyrazino[2,1-f]purine-2,4(1H,3H)-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%	With N-ethyl-N,N-diisopropylamine In 1,2-dimethoxyethane at 20℃;	5.1.2. General procedure of the synthesis of tetrahydropyrazino[2,1-f]purinediones 6-63 General procedure: 7-(2-Bromoethyl)-8-(hydroxymethyl)-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione (4) (100 mg, 0.32 mmol) was dissolved in dryCH2Cl2 (30 mL) and cooled to 0 C. A solution of PBr3 (90 lL,0.94 mmol) in dry CH2Cl2 (20 mL) was added dropwise. The solutionwas allowed to warm to rt and stirred for 1 h. Then it was cooled to0 C again and the excess of PBr3 was carefully hydrolyzed by slowaddition of saturated aq NaHCO3 solution (5 mL). The pH was set at8 by addition of more saturated aq NaHCO3 solution. Then, theorganic layer was separated and the aqueous layer extracted withCH2Cl2 (2 50 mL). The combined organic extracts were dried overNa2SO4 and the solvent was removed under reduced pressure. Thecrude 7-(2-bromoethyl)-8-bromo-1,3-dimethylpurine-2,4-dione (5) was dissolved in a mixture of dimethoxyethane (10 mL) anddiisopropylethylamine (DIPEA) (0.5 mL). Then, the appropriateamine (0.64 mmol)wasadded and the solutionwasstirred overnightat rt. The volatiles were removed under reduced pressure andtetrahydropyrazino[2,1-f]purinediones 6-63 precipitated uponaddition ofH2O(20 mL). For purification, thecompounds were eitherfiltered off and washed with H2O (3 5 mL) and subsequently withdiethylether (3 10 mL), or subjected to column chromatography(silica gel, gradient of CH2Cl2/MeOH 1:0 to 40:1).

Reference： [1]Brunschweiger, Andreas; Koch, Pierre; Schlenk, Miriam; Rafehi, Muhammad; Radjainia, Hamid; Küppers, Petra; Hinz, Sonja; Pineda, Felipe; Wiese, Michael; Hockemeyer, Jörg; Heer, Jag; Denonne, Frédéric; Müller, Christa E. [Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 21, p. 5462 - 5480]

75
2,6-dimethylimidazo[1,2-a]pyrimidine-3-carboxylic acid [ No CAS ]
[ 1758-46-9 ]
2,6-dimethyl-N-[(2-phenoxy)ethyl]imidazo[1,2-a]pyridine-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59.9%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 10h; Inert atmosphere;
58.9%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 10h;	1 2,6-dimethyl-N-[(2-phenoxy)ethyl]imidazo[1,2-a]pyridine-3-carboxamide 2,6-Dimethyl-N- [(2-phenoxy)ethyl] imidazo [1,2-a] pyridine-amide[0067] the mixture of 2,6-dimethylimidazo [1, 2-a] pyridine-3-carboxylic acid(0.13g,0.7mmol) , Phenoxyethylamine (0.29g,2.1mmol), 1- (3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride(EDCI0. 16g0. 84mmol) and1-hydroxybenzotriazole monohydrate(H0BT0.11g,0. 84mmol) and dichloromethane (10ml) was stirred for 10h at roomtemperature. Filtration filtrate was washed with saturated sodium bicarbonatesolution. Concentrated then residue was subjected to columnchromatography separation to obtain a off-white solid 0.127 g (yield: 58.9%),

Reference： [1]Wu, Zhaoyang; Lu, Yu; Li, Linhu; Zhao, Rui; Wang, Bin; Lv, Kai; Liu, Mingliang; You, Xuefu [ACS Medicinal Chemistry Letters, 2016, vol. 7, # 12, p. 1130 - 1133]
[2]Current Patent Assignee: CHINESE ACADEMY OF MEDICAL SCIENCES; ZHEJIANG STARRY PHARMACEUTICAL CO LTD - CN103965193, 2016, B Location in patent: Paragraph 0066-0067

76
[ 98-74-8 ]
[ 1758-46-9 ]
[ 296274-46-9 ]

Yield	Reaction Conditions	Operation in experiment
96%	Stage #1: 2-phenoxyethanamine With triethylamine In dichloromethane at 0℃; for 0.166667h; Stage #2: 4-Nitrobenzenesulfonyl chloride In dichloromethane at 20℃; for 2h;	3.6 4.2.1. Sulfonamide synthesis (Procedure A) General procedure: A solution of 3,4-dimethoxybenzylamine 4 or 2-phenoxyethylamine10 (1.2 equiv.) in MC was cooled to 0 C and triethylamine(2.4 equiv.) was added. The resulting solution was stirred for10 min and 4-nitrobenzenesulfonyl chloride 3 (1 equiv.) was added to the mixture and then stirred for 2 h at room temperature. The reaction was quenched with water and extracted with EtOAc twice.The combined organic extracts were dried over MgSO4, filtered,and evaporated in vacuo. The residue was purified by column chromatography over silica gel to afford the corresponding sulfonamide product.

Reference： [1]Yoon, Suyoung; Kim, Jong Hyun; Koh, Yura; Tran, Phuong-Thao; Ann, Jihyae; Yoon, Ina; Jang, Jayun; Kim, Won Kyung; Lee, Sangkook; Lee, Jiyoun; Kim, Sunghoon; Lee, Jeewoo [Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 15, p. 4145 - 4152]

77
[ 371-62-0 ]
[ 1758-46-9 ]
C₁₀H₁₄FNO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; sodium hydrogencarbonate In tert-Amyl alcohol at 100℃; for 24h; Inert atmosphere;	6 Example 6 Under nitrogen protection,To the pressure tube was added [Cp * IrCl2] 20.006 mmol,2-phenoxyethylamine 0.3 mmol, fluoroethanol 0.33 mmol,0.006 mmol of sodium bicarbonate and 0.5 mL of t-amyl alcohol,Heated to 100 ° C and reacted for 24 h. After completion of the reaction, the mixture was allowed to stand at room temperature, and a small amount of water was added thereto, and the mixture was extracted three times with 15 mL of ethyl acetate. The organic phases were combined and washed with saturated brine And dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the yield of the secondary amine was 81% by column chromatography.

Reference： [1]Current Patent Assignee: NANJING UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN106748802, 2017, A Location in patent: Paragraph 0034; 0035; 0036

78
[ 4023-02-3 ]
[ 1758-46-9 ]
[ 46231-41-8 ]

Yield	Reaction Conditions	Operation in experiment
49%	With N-ethyl-N,N-diisopropylamine In 1,4-dioxane; water for 8h; Reflux;	21 Experimental 21. 1-(2-Phenoxyethyl)guanidine [0332] A mixture of 2-phenoxyethan-1-amine (10 mmol, 1.0 equiv), 1H-pyrazole-1-carboxamidine hydrochloride (15 mmol, 1.5 equiv, 1 M) and DIPEA (1.5 equiv) in 1,4-dioxane/H20 (2:1) was refluxed for 8 hours, cooled down to r.t. and evaporated to dryness. Anorange oily residue was treated with water and resulting solution was saturated with solid K2C03 to induce the precipitation of free guanidine. Formed precipitate was filtered off, washed withcold water and dried on a rotary evaporator to afford a title compound. Yield: 0.878 g (49%).

Reference： [1]Current Patent Assignee: EVERON BIOSCIENCES INC - WO2017/189553, 2017, A1 Location in patent: Paragraph 0331; 0332

79
2-(((2-((1R,3S,4S)-4-methyl-3-(prop-1-en-2-yl)-4-vinylcyclohexyl)allyl)oxy)methyl)oxirane [ No CAS ]
[ 1758-46-9 ]
1-((2-((1R,3S,4S)-4-Methyl-3-(prop-1-en-2-yl)-4-vinylcyclohexyl)allyl)oxy)-3-((2-phenoxyethyl)amino)propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With zinc perchlorate In methanol at 80℃; for 1h;	15 Example 1 Synthesis of N, N-diethylisopropanolamine-β-elemene General procedure: 0.5 mmol of propylene oxide β-elemene and 1.5 mmol of diethylamine were dissolved in 1 mL of methanol,0.05 mmol of Zn (ClO 4) 2 .6H 2 O was added and stirred at 80 ° C. for 1 h. Cool to room temperature, add water, extract with methylene chloride, dry over anhydrous sodium sulfate,The methylene chloride was distilled off under reduced pressure and the residue was subjected to column chromatography with methylene chloride: methanol = 40: 1 to give a light yellow liquid product in a yield of 66%.

Reference： [1]Current Patent Assignee: CSPC BROAD DALIAN PHARMACEUTICAL - CN106928074, 2017, A Location in patent: Paragraph 0100; 0101; 0102; 0142; 0143; 0144

80
[ 1758-46-9 ]
N-(2-phenoxyethyl)sulfamoyl fluoride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With 1-(fluorosulfuryl)-2,3-dimethyl-1H-imidazol-3-ium trifluoromethanesulfonate In acetonitrile at 0 - 20℃; for 4h;
92%	With 1-(fluorosulfuryl)-2,3-dimethyl-1H-imidazol-3-ium trifluoromethanesulfonate In acetonitrile at 20℃; for 4h; Cooling with ice;	67 Example 67 Preparation of 2-phenoxy-1-ethylamine sulfonyl fluoride 2-Phenyloxyethylamine [Compound 141] (137 mg, 1 mmol)Soluble in acetonitrile (3mL)1-(Fluorosulfonyl)-2,3-dimethyl-1H-imidazole trifluoromethanesulfonate [Compound 4] (328 mg, 1 mmol) was added under ice-cooling.After the completion of the withdrawal of the ice bath,After 4 hours at room temperature, the reaction was completed by GC-MS.Water (30 mL) was added to the reaction solution.Extract with ethyl acetate (20mL×3)After combining the organic phases with water (20 mL),Saturated brine (20mL) was washed and dried over anhydrous sodium sulfate.Filter paper, the filtrate was concentrated by rotary evaporator.The oil pump dries the solvent,Obtained as a pale yellow solid 2-phenoxy-1-ethylamine sulfonyl fluoride[Compound 142](203mg, 92%)(Scheme 67).

Reference： [1]Guo, Taijie; Meng, Genyi; Zhan, Xiongjie; Yang, Qian; Ma, Tiancheng; Xu, Long; Sharpless, K. Barry; Dong, Jiajia [Angewandte Chemie - International Edition, 2018, vol. 57, # 10, p. 2605 - 2610][Angew. Chem., 2018, vol. 130, # 10, p. 2635 - 2640,6]
[2]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES - CN107857730, 2018, A Location in patent: Paragraph 0474; 0475; 0476; 0477; 0478; 0479

81
[ 1620093-70-0 ]
[ 1758-46-9 ]
2-furan-2-yl-5-methylamino-[1,2,4]triazolo[1,5-c]pyrimidine-8-carboxylic acid (2-phenoxy-ethyl)-amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
34%	Stage #1: 2-furan-2-yl-5-methylamino-[1,2,4]triazolo[1,5-c]pyrimidine-8-carboxylic acid With trichlorophosphate In pyridine at -10℃; Stage #2: 2-phenoxyethanamine In pyridine at 20℃; for 16h;	4.4.1 General procedure for the synthesis of ester and amide derivatives 3-32 General procedure: To 2.45mmol of carboxylic acid derivatives (47) dissolved in 0.7mL of dry pyridine were added 0.1mL of phosphorous oxychloride. The mixture was led to-10°C and then was added 39.2mmol of the appropriate amine or alcohol. The reaction was stirred at room temperature for 16h, then was added water and the product extracted with ethylacetate. The organic layer was washed with a NaHCO3 solution, dried and concentrated. The residue was purified by flash chromatography (Ethyl acetate 9: Light Petroleum 1).

Reference： [1]Federico, Stephanie; Margiotta, Enrico; Salmaso, Veronica; Pastorin, Giorgia; Kachler, Sonja; Klotz, Karl-Norbert; Moro, Stefano; Spalluto, Giampiero [European Journal of Medicinal Chemistry, 2018, vol. 157, p. 837 - 851]

82
(R)-2-{4-[(3-chloro-5-trifluoromethyl pyridin-2-yl)oxy]phenoxy}propanoic acid chloride [ No CAS ]
[ 1758-46-9 ]
(R)-2-N-(2-phenoxyethyl)-2-(4-[(3-chloro-5-trifluoromethylpyridin-2-yl)oxy]phenoxy)propionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80.1%	With dmap; triethylamine In dichloromethane at 20℃; for 1h;	(R)-2-N-(2-Phenoxyethyl)-2-[4-((3-Chloro-5-trifluoromethylpyridin-2-yl)oxy]phenoxy)propionamides (3a) A mixture of (0.137 g, 1 mmol)-2-phenoxy ethylamine-(1.0 mmol) triethylamine-and catalyst amount of DMAP was dissolved in 20 mL dichloromethane, then (R)-2-{4-[(3-chloro-5-trifluoromethylpyridin-2-yl)oxy]phenoxy}propanoic acyl chloride was added dropwise and stirred for 1 h at room temperature. When the reaction was complete, the mixture was washed with water and brine, dried over anhydrous sodium sulfate, and vacuumed to distillate solvent. Moreover, the crude product was purified with column chromatography silica gel using PE and EtOAc as eluent to give white solid 3a-m.p. 138~140°C, yield 80.1% [α]20 D +20.33° (c 1, CH2Cl2); 1 H NMR (400 MHz, CDCl3) δ-7.85 (d, J = 2.2 Hz, 1H, pyridine), 7.50 (dd, J1 = 9.0, J2 = 2.2 Hz, 1H, pyridine), 7.29 (s, 1H, C6H5), 7.25 (s, 1H, C6H5), 7.04 (d, J = 9.0 Hz, 2H, C6H4), 6.94 (t, J = 9.0 Hz, 3H, C6H5), 6.84 (d, J = 8.7 Hz, 2H, C6H4), 4.67 (q, J = 6.8 Hz, 1H, CHCH3), 3.97~4.10 (m, 2H, COOCH2), 3.70 (m, 2H, OCH2), 1.58 (d, J = 6.8 Hz, 3H, CH3). EI-MS m/z 480.1 [M + ]. Analysis calculated for C21H21ClFN3O3S C 64.78, H 4.78, N 9.06; found C 64.76, H 4.70, N 9.03.
80.1%	With dmap; triethylamine In dichloromethane at 20℃; for 1.15h;	1 (R)-2-N-(2-phenoxyethyl)-2-[4-(3-chloro-5-trifluoromethylpyridin-2-oxyphenoxy)propanamide (Compound I) preparation 0.137 g (1 mmol) of phenoxyethylamine, 1.0 mmol of triethylamine, Catalytic amount of 4-dimethylaminopyridine (DMAP), 20mL of dichloromethane, add 1.2mmol under ice bath (R)-[4-(3-Chloro-5-trifluoromethylpyridin-2-oxyphenoxy)propanoyl chloride in dichloromethane, about 15 min, The reaction was carried out for 1 h at room temperature. After the reaction is completed, the organic layer is washed with water. Washed with saturated brine, dried, desolved, The crude product was subjected to column chromatography [V petroleum ether: V ethyl acetate = 7:1 to 5:1] to give (R)-N-(4-tert-butylthiazol-2-yl)-2-[4- (3-chloro-5-trifluoromethylpyridin-2-oxyphenoxy)propanamide, M.p. 138-140 ° C, yield 80.1%.

Reference： [1]Hui, Yang Zi [Indian Journal of Heterocyclic Chemistry, 2018, vol. 28, # 3, p. 385 - 387]
[2]Current Patent Assignee: ANHUI AGRICULTURAL UNIVERSITY - CN108689921, 2018, A Location in patent: Paragraph 0048-0049

83
(R)-2-(4-((6-chloroquinoxalin-2-yl)oxy)phenoxy)propionic acid chloride [ No CAS ]
[ 1758-46-9 ]
(R)-2-N-(2-phenoxyethyl)-2-(4-[(6-chloroquinoxaline-2-yl)oxy]phenoxy)propionamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78.3%	With dmap; triethylamine In dichloromethane at 20℃; for 2h;	(R)-2-N-(2-Phenoxyethyl)-2-[4-((3-Chloro-5-trifluoromethylpyridin-2-yl)oxy]phenoxy)propionamides (3a) General procedure: A mixture of (0.137 g, 1 mmol)-2-phenoxy ethylamine-(1.0 mmol) triethylamine-and catalyst amount of DMAP was dissolved in 20 mL dichloromethane, then (R)-2-{4-[(3-chloro-5-trifluoromethylpyridin-2-yl)oxy]phenoxy}propanoic acyl chloride was added dropwise and stirred for 1 h at room temperature. When the reaction was complete, the mixture was washed with water and brine, dried over anhydrous sodium sulfate, and vacuumed to distillate solvent. Moreover, the crude product was purified with column chromatography silica gel using PE and EtOAc as eluent to give white solid 3a-m.p. 138~140°C, yield 80.1% [α]20 D +20.33° (c 1, CH2Cl2); 1 H NMR (400 MHz, CDCl3) δ-7.85 (d, J = 2.2 Hz, 1H, pyridine), 7.50 (dd, J1 = 9.0, J2 = 2.2 Hz, 1H, pyridine), 7.29 (s, 1H, C6H5), 7.25 (s, 1H, C6H5), 7.04 (d, J = 9.0 Hz, 2H, C6H4), 6.94 (t, J = 9.0 Hz, 3H, C6H5), 6.84 (d, J = 8.7 Hz, 2H, C6H4), 4.67 (q, J = 6.8 Hz, 1H, CHCH3), 3.97~4.10 (m, 2H, COOCH2), 3.70 (m, 2H, OCH2), 1.58 (d, J = 6.8 Hz, 3H, CH3). EI-MS m/z 480.1 [M + ]. Analysis calculated for C21H21ClFN3O3S C 64.78, H 4.78, N 9.06; found C 64.76, H 4.70, N 9.03.
78.3%	With dmap In dichloromethane at 20℃; for 1.5h;	2 Example 2: (R)-2-N-(2-phenoxyethyl)-2-[4-(6-chloroquinoxalin-2-yloxy)phenoxy]propanamide (Compound II) preparation 0.137 g (1 mmol) of phenoxyethylamine, 1.0 mmol of triethylamine, Catalytic amount of 4-dimethylaminopyridine (DMAP), 20 mL of dichloromethane, 1.2 mmol of (R)-2-[4-(6-chloroquinoxalin-2-yloxy)phenoxy]propanoyl chloride was added dropwise under ice bath The dichloromethane solution was dissolved in about 15 minutes and allowed to react at room temperature for 1 hour. After the reaction is completed, the organic layer is washed with water and washed with saturated brine. Dry, desolvent, The crude product was subjected to column chromatography [V petroleum ether: V ethyl acetate = 7:1 to 5:1] to afford white (R)-2-N-(2-phenoxyethyl)-2-[4-(6 -chloroquinoxaline-2-yloxy)phenoxy]propanamide, mp 150-153 ° C, yield 78.3%,

Reference： [1]Hui, Yang Zi [Indian Journal of Heterocyclic Chemistry, 2018, vol. 28, # 3, p. 385 - 387]
[2]Current Patent Assignee: ANHUI AGRICULTURAL UNIVERSITY - CN108689921, 2018, A Location in patent: Paragraph 0051-0052

84
trans-3-phenyl-1,4-dioxane-2-carboxylic acid [ No CAS ]
[ 1758-46-9 ]
trans-N-(2-phenoxyethyl)-3-phenyl-1,4-dioxane-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	Stage #1: trans-3-phenyl-1,4-dioxane-2-carboxylic acid With chloroformic acid ethyl ester; triethylamine In chloroform at 0℃; for 0.5h; Stage #2: 2-phenoxyethanamine In chloroform at 20℃; for 3h;	1 4.1.11. General procedure for the synthesis of compounds 26-33 General procedure: Et3N (4.3 mmol) and 97% EtOCOCl (4.3 mmol) in dry CHCl3(25 mL) were added to a solution of the suitable carboxylic acid 24a,24b or 25 (4.3 mmol) at 0 °C. After 30 min at 0 °C under stirring asolution of the suitable amine (2-phenoxyethanamine, 2-(2-methoxyphenoxy)ethanamine [37], 2-(2,6-dimethoxyphenoxy)ethanamine [38], or 1-(2-methoxyphenyl)piperazine) (4.3 mmol)in dry CHCl3 (10 mL) was added and the reaction mixture was left atroom temperature for 3 h. The solution was washed with 2 N HCl and 2 N NaOH. The organic layer was dried over Na2SO4. After evaporation of the solvent the residue was purified by column chromatography eluting with cyclohexane/EtOAc (7:3). 4.1.11.1. trans-N-(2-Phenoxyethyl)-3-phenyl-1,4-dioxane-2-carboxamide (26a). This compound was prepared starting from 24a and 2-phenoxyethanamine: a solid was obtained (73% yield;mp 109-110 °C). 1H NMR (CDCl3) d 3.56 (m, 2H), 3.84e4.01 (m, 6H),4.08 (d, 1H, J 9.0 Hz), 4.42 (d, 1H, J 9.0 Hz), 6.60 (br t, 1H,exchangeable with D2O), 6.86e7.38 (m, 10H). ESI/MS: m/z 328.2[M H]. Anal. Calcd for C19H21NO4: C, 69.71%; H, 6.47%; N, 4.28%.Found: C, 69.87%; H, 6.23%; N, 4.39%.

Reference： [1]Del Bello, Fabio; Bonifazi, Alessandro; Giorgioni, Gianfabio; Quaglia, Wilma; Amantini, Consuelo; Morelli, Maria Beatrice; Santoni, Giorgio; Battiti, Francisco O.; Vistoli, Giulio; Cilia, Antonio; Piergentili, Alessandro [European Journal of Medicinal Chemistry, 2019, vol. 168, p. 461 - 473]

85
cis-3-phenyl-1,4-dioxane-2-carboxylic acid [ No CAS ]
[ 1758-46-9 ]
cis-N-(2-phenoxyethyl)-3-phenyl-1,4-dioxane-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	Stage #1: cis-3-phenyl-1,4-dioxane-2-carboxylic acid With chloroformic acid ethyl ester; triethylamine In chloroform at 0℃; for 0.5h; Stage #2: 2-phenoxyethanamine In chloroform at 20℃; for 3h;	2 4.1.11. General procedure for the synthesis of compounds 26-33 General procedure: Et3N (4.3 mmol) and 97% EtOCOCl (4.3 mmol) in dry CHCl3(25 mL) were added to a solution of the suitable carboxylic acid 24a,24b or 25 (4.3 mmol) at 0 °C. After 30 min at 0 °C under stirring asolution of the suitable amine (2-phenoxyethanamine, 2-(2-methoxyphenoxy)ethanamine [37], 2-(2,6-dimethoxyphenoxy)ethanamine [38], or 1-(2-methoxyphenyl)piperazine) (4.3 mmol)in dry CHCl3 (10 mL) was added and the reaction mixture was left atroom temperature for 3 h. The solution was washed with 2 N HCl and 2 N NaOH. The organic layer was dried over Na2SO4. After evaporation of the solvent the residue was purified by column chromatography eluting with cyclohexane/EtOAc (7:3).

Reference： [1]Del Bello, Fabio; Bonifazi, Alessandro; Giorgioni, Gianfabio; Quaglia, Wilma; Amantini, Consuelo; Morelli, Maria Beatrice; Santoni, Giorgio; Battiti, Francisco O.; Vistoli, Giulio; Cilia, Antonio; Piergentili, Alessandro [European Journal of Medicinal Chemistry, 2019, vol. 168, p. 461 - 473]

86
3,3-diphenyl-1,4-dioxane-2-carboxylic acid [ No CAS ]
[ 1758-46-9 ]
N-(2-phenoxyethyl)-3,3-diphenyl-1,4-dioxane-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	Stage #1: 3,3-diphenyl-1,4-dioxane-2-carboxylic acid With chloroformic acid ethyl ester; triethylamine In chloroform at 0℃; for 0.5h; Stage #2: 2-phenoxyethanamine In chloroform at 20℃; for 3h;	7 4.1.11. General procedure for the synthesis of compounds 26-33 General procedure: Et3N (4.3 mmol) and 97% EtOCOCl (4.3 mmol) in dry CHCl3(25 mL) were added to a solution of the suitable carboxylic acid 24a,24b or 25 (4.3 mmol) at 0 °C. After 30 min at 0 °C under stirring asolution of the suitable amine (2-phenoxyethanamine, 2-(2-methoxyphenoxy)ethanamine [37], 2-(2,6-dimethoxyphenoxy)ethanamine [38], or 1-(2-methoxyphenyl)piperazine) (4.3 mmol)in dry CHCl3 (10 mL) was added and the reaction mixture was left atroom temperature for 3 h. The solution was washed with 2 N HCl and 2 N NaOH. The organic layer was dried over Na2SO4. After evaporation of the solvent the residue was purified by column chromatography eluting with cyclohexane/EtOAc (7:3).

Reference： [1]Del Bello, Fabio; Bonifazi, Alessandro; Giorgioni, Gianfabio; Quaglia, Wilma; Amantini, Consuelo; Morelli, Maria Beatrice; Santoni, Giorgio; Battiti, Francisco O.; Vistoli, Giulio; Cilia, Antonio; Piergentili, Alessandro [European Journal of Medicinal Chemistry, 2019, vol. 168, p. 461 - 473]

87
[ 109-09-1 ]
[ 1758-46-9 ]
N‑(2‑phenoxyethyl)‑N‑(pyridin‑2‑yl)pyridin‑2‑amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With triethylamine In methanol at 25℃; for 72h; Inert atmosphere; Schlenk technique;	Synthesis of ligands (L1-L4) General procedure: A solution of 2-phenoxyethylamine (1.31 mL, 10 mmol) in methanol (10 mL) was added to a solution of triethylamine(Et3N) (2.76 mL, 20 mmol) in methanol (10 mL) at 0 °C. A solution of 2-chloropyridine (3.80 mL, 40 mmol) in methanol(10 mL) was then added at 0 °C under N2. After being stirred for 30 min, the reaction mixture was heated to 25 °C and stirred for 3 days. Then, the solvent was evaporated under reduced pressure to afford a yellow solid L1 washed with methanol and dried under vacuum. Yield: 2.31 g (79%).FTIR data (KBr, pellet, cm-1): υ 3335, 3057, 2922, 1573,1436, 1243. 1H NMR (400 MHz, CDCl3,ppm): δ 3.94 (t,2H, CH2,J 47.8 Hz), 4.59 (t, 2H, CH2),6.85 (t, 2H, Py-H),6.87 (d, 2H, Py-H, J 7.1 Hz), 7.15 (d, 2H, Ph-H), 7.26 (t,1H, Ph-H), 7.54 (t, 2H, Ph-H), 7.57 (t, 2H, Py-H), 8.33 (d,2H, Py-H). 13C NMR (100 MHz, CDCl3,ppm): δ 42.83,67.63, 115.72, 116.79, 117.17, 121.13, 130.02, 137.32,147.14, 157.30, 159.39. ESI-MS (m/z): 291.16 [L1 + H]+.Anal. Calcd for C18H17N3O(Found) %: C, 74.23 (74.01); H,5.84 (5.71); N, 14.43 (14.13).

Reference： [1]Wang, Jun; Liu, Jinyi; Chen, Liduo; Lan, Tianyu; Wang, Libo [Transition Metal Chemistry, 2019, vol. 44, # 7, p. 681 - 688]

88
[ 3678-62-4 ]
[ 1758-46-9 ]
4‑methyl‑N‑(4‑methylpyridin‑2‑yl)‑N‑(2‑phenoxyethyl)pyridin‑2‑amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With triethylamine In methanol at 25℃; for 72h; Inert atmosphere; Schlenk technique;	Synthesis of ligands (L1-L4) General procedure: A solution of 2-phenoxyethylamine (1.31 mL, 10 mmol) in methanol (10 mL) was added to a solution of triethylamine(Et3N) (2.76 mL, 20 mmol) in methanol (10 mL) at 0 °C. A solution of 2-chloropyridine (3.80 mL, 40 mmol) in methanol(10 mL) was then added at 0 °C under N2. After being stirred for 30 min, the reaction mixture was heated to 25 °C and stirred for 3 days. Then, the solvent was evaporated under reduced pressure to afford a yellow solid L1 washed with methanol and dried under vacuum.

Reference： [1]Wang, Jun; Liu, Jinyi; Chen, Liduo; Lan, Tianyu; Wang, Libo [Transition Metal Chemistry, 2019, vol. 44, # 7, p. 681 - 688]

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
Accessible (Haz class 3, 4, 5 or 8), International	USD 200+

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

CAS No. :	1758-46-9	MDL No. :	MFCD00052975
Formula :	C₈H₁₁NO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	IMLAIXAZMVDRGA-UHFFFAOYSA-N
M.W :	137.18	Pubchem ID :	15651
Synonyms :

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.25
Num. rotatable bonds :	3
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	39.82
TPSA :	21.26 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.49 cm/s

[ CAS No. 1758-46-9 ] {[proInfo.proName]}

Quality Control of [ 1758-46-9 ]

Related Doc. of [ 1758-46-9 ]

Product Details of [ 1758-46-9 ]

Calculated chemistry of [ 1758-46-9 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 1758-46-9 ]

Application In Synthesis of [ 1758-46-9 ]

[ 1758-46-9 ] Synthesis Path-Downstream 1~88

Related Functional Groups of
[ 1758-46-9 ]

Aryls

Ethers

Amines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Log Po/w (iLOGP) :	-3.77
Log Po/w (XLOGP3) :	0.9
Log Po/w (WLOGP) :	1.12
Log Po/w (MLOGP) :	1.21
Log Po/w (SILICOS-IT) :	1.3
Consensus Log Po/w :	0.15

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Log S (ESOL) :	-1.5
Solubility :	4.33 mg/ml ; 0.0318 mol/l
Class :	Very soluble
Log S (Ali) :	-0.93
Solubility :	15.9 mg/ml ; 0.117 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.56
Solubility :	0.377 mg/ml ; 0.00277 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.0

Signal Word:	Danger	Class:	8
Precautionary Statements:	P280-P305+P351+P338-P310	UN#:	2735
Hazard Statements:	H314	Packing Group:	Ⅲ
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

[ CAS No. 1758-46-9 ] {[proInfo.proName]}

Quality Control of [ 1758-46-9 ]

Related Doc. of [ 1758-46-9 ]

Product Details of [ 1758-46-9 ]

Calculated chemistry of [ 1758-46-9 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 1758-46-9 ]

Application In Synthesis of [ 1758-46-9 ]

[ 1758-46-9 ] Synthesis Path-Downstream 1~88

Related Functional Groups of [ 1758-46-9 ]

Aryls

Ethers

Amines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 1758-46-9 ]