Name: 37859-25-9|2-(Naphthalen-2-yl)acetyl chloride|95%
Brand: Ambeed
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[ 37859-25-9 ]

Yield	Reaction Conditions	Operation in experiment
99%	With oxalyl dichloride In dichloromethane at 20℃; for 3h;	14.1 Oxalyl chloride (7.0 mL, 80.2 mmol)was added under nitrogen to a solution of 2-naphthylacetic acid (3.00 g, 16.1 mmol) in 150 mL of methylene chloride at room temperature. A catalytic amount of DMF (10 uL) was added andthe R£tiln''sMilQ iic^eliprSttie for 3 h. The solvent and excess oxalyl chloride were removed under reduced pressure. To remove any residual oxalyl chloride the residue was taken up in benzene and then concentrated under reduced pressure to give naphthalen-2-yl-acetyl chloride (3.20 g, 99%) as a yellow solid that was used in the next step without additional purification.
78%	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 1h;	245; 265 At 0°C., oxalyl chloride (0.104 mE, 1.19 mmol) and one drop of DMF were added to a soln of 2-naphthaleneacetic acid (53 mg, 0.29 mmol) in CH2C12 (6 mE). The mixture was stirred at it for 1 h and concentrated. The residue was dissolved in CH2C12 (2.5 mE) and added dropwise to a soln of Ex. 263 (100 mg, 0.24 mmol) and i-Pr2NEt (0.204 mE, 1.19 mmol) in CH2C12 (3.5 mE). The mixture was stirred at 0° C. for 1 h followed by an aqueous workup (CH2C12, sat. aq. NaHCO3 soln; Na2504) and FC (CH2C12/1 -PrOH 100:0 to 95:5) to yield Ex. 265 (110mg, 78%).Data of Ex. 265: cf. Table 28b ‘H-NMR (DMSO-d5): 8.54 (d, J=7.5, 1H); 7.89-7.85 (m, 3H); 7.78 (s, 1H); 7.52-7.44 (m, 3H); 7.40 (d, J=5.5, 1H); 7.09 (d, J=5.5, 1H); 6.44 (s, 1H); 5.14 (d, J=4.9, 1H);4.65 (br. t, J=8.0, 1H); 4.40-4.31 (m, 2H); 4.11 (q, J ca 5.8, 1H); 4.03 (m, 1H), 3.84 (m, 1H); 3.84 (s, 3H); 3.68 (s, 2H);3.64 (m, 1 H); ca 3.30 (m, 1H, partially superimposed by H20 signal); 3.17 (dd, J=6.3, 10.5, 1H); 2.91 (s, 3H); 2.35 (m, 1H); 2.18 (m, 1H); 1.91-1.82 (m, 2H).
	With thionyl chloride

	With thionyl chloride
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane for 0.416667h;
	With oxalyl dichloride; N,N-dimethyl-formamide
	With thionyl chloride for 1h; Heating;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane for 2.5h; Ambient temperature;
	With thionyl chloride Heating;
	With oxalyl dichloride In dichloromethane
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane
	With oxalyl dichloride In tetrahydrofuran at 25℃; for 2h;
	With thionyl chloride In dichloromethane; N,N-dimethyl-formamide at 20℃;
	With thionyl chloride In benzene for 1h; Heating;
	With thionyl chloride; N,N-dimethyl-formamide In ethyl acetate
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 1h;
	With oxalyl dichloride In ethyl acetate
	With thionyl chloride for 12h; Heating / reflux;	17.A Step A: (Naphth-2-yl)acetyl Chloride A mixture of 30 mmol of naphth-2-ylacetic acid and 5 ml of thionyl chloride is heated at reflux under an argon atmosphere for 12 hours. After cooling the reaction mixture and evaporation, the residue obtained is taken up in anhydrous methylene chloride until the excess of thionyl chloride has been eliminated, to yield the title product in the form of a yellow oil.
	With thionyl chloride	A.R.P.R.106891 Example A RPR106891 2-Naphthylacetyl chloride is obtained from a mixture of 0.38 g of 2-naphthylacetic acid and 4 cm3 of thionyl chloride, which is brought to reflux for 20 minutes. After concentrating to dryness under reduced pressure (2.7 kPa), 0.41 g of an oil is obtained, which is used in the crude state in the subsequent syntheses.
	With thionyl chloride at 80℃; for 1h;
	With thionyl chloride In methanol at 0 - 20℃; Inert atmosphere;
	With oxalyl dichloride; N,N-dimethyl-formamide In tetrahydrofuran at 0 - 20℃;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 2h;
	With thionyl chloride In dichloromethane at 20℃; for 16h;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; Inert atmosphere;
	With thionyl chloride In dichloromethane for 6h; Reflux;
	With oxalyl dichloride
	With thionyl chloride for 3h; Reflux; Inert atmosphere;
	With thionyl chloride; N,N-dimethyl-formamide In toluene at 70℃; for 3h; Inert atmosphere;
	With thionyl chloride at 90℃;
	With oxalyl dichloride; N,N-dimethyl-formamide Inert atmosphere;
	With thionyl chloride for 2h; Reflux;
	With thionyl chloride In dichloromethane at 80℃; for 2h; Inert atmosphere;
	With thionyl chloride; N,N-dimethyl-formamide In toluene at 40℃; for 0.5h; Inert atmosphere;
	for 1h;
	With thionyl chloride at 90℃; for 1h;
	With oxalyl dichloride In dichloromethane at 0 - 20℃; for 1h; Inert atmosphere;	General Procedure D. General procedure: The appropriate carboxylic acid (1.0 equiv) was treated with oxalyl chloridie (1.1 equiv) in CH2Cl2 (0.5 M) at 0° C. The reaction mixture was stirred at room temperature for 1 h. The solvent was removed under N2 and the acid chloride was redissolved in anhydrous CH2Cl2 (0.5 M). The appropriate pyrazole (1.0 equiv) was dissolved in CH2Cl2 and cooled to 0° C. The acid chloride was added dropwise and the reaction mixture was stirred at room temperature for 3 h. The mixture was diluted withEtOAc, washed with saturated aqueous NaCl, and dried over Na2SO4. Evaporation under reduced pressure yielded the crude product that was purified by flash chromatography(SiO2).
	With thionyl chloride at 90℃; for 1h;
	With thionyl chloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 4h;	General procedure: To a solution of substituted phenyl acetic acid or naphthylacetic acid (200 mg, 1.1 mmol) in dry DCM (10 ml) was added SOCl2 (128 mg, 1.1 mmol) and DMF (1 drop). The mixture was stirred at room temperature for 4 hours, following which the solvent was removed in vacuo. Dry DCM (10 ml) was added to re-dissolve the residue. After that, the solution was dropwise added into the mixture of 4-methoxybenzyl hydroxylamine (3) (165 mg, 1.1 mmol) and Et3N (223 mg, 2.2 mmol) in DCM (10 ml) and stirred at room temperature for 1h. The reaction mixture was quenched with water (20 ml) and then extracted with DCM (3 x 20ml). The combined organic layers was washed with brine and dried with anhydrous Na2SO4. The solvent was removed in vacuo. The crude product was purified with column chromatography (33% EA/Petroleum ether) to obtain a white solid in yields range from 68 to 88% yield.
	With thionyl chloride In benzene Reflux;
	With thionyl chloride In dichloromethane at 55℃; Inert atmosphere;
	With thionyl chloride In dichloromethane at 0 - 20℃; Inert atmosphere;
	With thionyl chloride at 25℃; Inert atmosphere;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 1h;	9.A To a solution of 5.0 g (26.9 rnmol) of 2-napthylacetic acid in 75 mL of dichloroniethane was added 2.60 mL (29.5 mmol) of oxalyl chloride followed by 0.20 mL (2.7 mmol) of N,N-dimethylformamide. The resulting solution was stirred at ambient temperature for 1 h and then all volatiles were removed in vacuo. The resulting residue was dissolved in 15 mL of dichloromethane and 15 mL of 2-methyl-2-propanol, and the resulting solution was stirred for 2.5 h. All volatiles were removed in vacuo and the crude residue was purified on a Biotage purification apparatus (silica gel, 7% ethyl acetate in hexanes) to afford the title compound as a colorless oil. LC/MS 243.1 (M+l).
	With oxalyl dichloride In dichloromethane at 0 - 20℃; for 1h; Inert atmosphere;	General procedure: The appropriate carboxylic acid (1.0 equiv) was treated with oxalylchloride (1.1 equiv) in CH2Cl2 (0.5 M) at 0 °C. The reaction mixture wasstirred at room temperature for 1 h. The solvent was removed under N2and the acid chloride (1 equiv) was dissolved in anhydrous CH2Cl2(0.5 M). The appropriate pyrazole (1.0 equiv) was dissolved in CH2Cl2(0.5 M) and cooled to 0 °C. The acid chloride (1 equiv) in CH2Cl2 (0.5 M) was added dropwise and the reaction mixture was stirred atroom temperature for 3 h. The mixture was diluted with EtOAc, washedwith saturated aqueous NaCl, and dried over Na2SO4. Evaporationunder reduced pressure yielded the crude product that was purified byflash chromatography (SiO2).
	With thionyl chloride at 90℃;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 2h;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0℃; for 1h;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 6h;
	With thionyl chloride at 80℃;
	With thionyl chloride at 20℃; for 2h;	General procedure for compounds 4a-h General procedure: Carboxylic acid (1a-h) (679.04 μmol) was dissolved inSOCl2 (2 mL). The mixture was stirred at room temperaturefor 2 h. After evaporation of the solvent, the intermediate(2a-h) was dissolved in anhydrous DCM (2 mL) and thenadded dropwise to another anhydrous DCM (10 mL) inwhich sulfonic aniline (3) (565.87 μmol) and DIPEA(188.94 μL) were dissolved. The mixture was stirred atroom temperature for 4 h and the precipitate was recoveredby vacuum filtration. The final compound was purified bycolumn chromatography using methanol/dichloromethane1:19 as eluents (4a, 4b, and 4g) or purified by stirring withthe ether (4c-f and 4h).
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 2h;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 2h;	General procedure for acid chloride formation (step f) General procedure: Toan oven-dried round bottom flask charged with 2-(4-chlorophenyl)acetic acid,56(500 mg, 2.93 mmol, 1.0 equiv.),and CH2Cl2(10 mL) was added oxalyl chloride(0.30 mL, 3.52mmol, 1.2 equiv.) dropwise followed by DMF (0.02 mL).The resulting mixture was allowed to stir at room temperature for 2 h.The solvent was removed under reduced pressure to give a yellow oily residue which was dissolved in THF (10 mL).
	With thionyl chloride In dichloromethane at 0 - 20℃; for 5h;
	With thionyl chloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 3h;
	With thionyl chloride In N,N-dimethyl-formamide; toluene at 40℃; for 3h; Inert atmosphere;	4 Example 4: Synthesis of Nitrile Compound In a nitrogen-substituted reactor were mixed 2-naphthylacetic acid (0.50 g) obtained in Example 1, thionyl chloride (0.38 g, 1.2 mole ratio to carboxylic acid compound) and toluene (2.5 mL, 5.0 volume ratio to carboxylic acid compound), one drop of N,N-dimethylformamide was added as a catalyst, and the mixture was reacted at 40° C. for 3 hr (acid chlorination).
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; Inert atmosphere;
	With thionyl chloride In benzene
	With thionyl chloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 2h;	2.5.1 Preparation of acyl chlorides General procedure: Corresponding acid (1.0 equiv, 10 mmol) was dissolved in 25 mL CH2Cl2 in a 100 mL round-bottom flask with a stir bar, one drop of DMF was added, then SOCl2(2.0 equiv, 20 mmol) was slowly added into the mixture at room temperature, the obtained solution was stirred for 2 h at room temperature. The title acyl chloride was obtained after evaporating the solvent and used without further purification.
	With thionyl chloride	2 Example 2 Example 2 In a nitrogen-substituted reactor were added 2-naphthylacetic acid (75.02 g) synthesized according to the method of Example 1(1), toluene (263 mL) (3.5 volume ratio to 2-naphthylacetic acid), and N,N-dimethylformamide (0.29 g) (0.01 mole ratio to 2-naphthylacetic acid), the mixture was heated, and thionyl chloride (50.3 g) (1.05 mole ratio to 2-naphthylacetic acid) was added at 35° C.-45° C. After reaction for 3 hr, the reaction mixture was concentrated and reaction starting material 1 containing 2-naphthylacetyl chloride was prepared.
	With thionyl chloride	4 Example 4 Example 4 In a nitrogen-substituted reactor were added 2-naphthylacetic acid (10.03 g) synthesized according to the method of Example 1(1), toluene (35 mL) (3.5 volume ratio to 2-naphthylacetic acid), and N,N-dimethylformamide (42 μL) (0.01 mole ratio to 2-naphthylacetic acid), the mixture was heated, and thionyl chloride (6.72 g) (1.05 mole ratio to 2-naphthylacetic acid) was added at 35° C.-45° C. After reacting for 2 hr, the mixture was cooled and filtered at room temperature, and the filtration residue was washed with toluene (5 mL). To the obtained filtrate and washing solution was added sulfolane (10 mL) (1 volume ratio to 2-naphthylacetic acid), the mixture was concentrated, and reaction starting material 1 containing 2-naphthylacetyl chloride was prepared.
	With thionyl chloride; N,N-dimethyl-formamide In toluene at 35 - 45℃; for 3h; Inert atmosphere;	2-6 Example 2 In a nitrogen-substituted reactor were added 2-naphthylacetic acid (75.02 g) synthesized according to the method of Example 1(1), toluene (263 mL) (3.5 volume ratio to 2-naphthylacetic acid), and N,N-dimethylformamide (0.29 g) (0.01 mole ratio to 2-naphthylacetic acid), the mixture was heated, and thionyl chloride (50.3 g) (1.05 mole ratio to 2-naphthylacetic acid) was added at 35° C.-45° C. After reaction for 3 hr, the reaction mixture was concentrated and reaction starting material 1 containing 2-naphthylacetyl chloride was prepared.
	With thionyl chloride In dichloromethane at 0℃; for 1h;	6 Compound 1 2-naphthylacetic acid (187.4 mg, 1.0 mmol) was suspended in DCM (4 mL) and placed in an ice bath. Thionyl chloride (365.5 pL, 5.0 mmol) was then added to the mixture, and the reaction mixture was allowed stir at 0 °C for 1 h. The reaction mixture was concentrated in vacuo and carried forward to the next step without further purification.
	With thionyl chloride In dichloromethane at 0℃; for 1h;	6 Compound 1 2-naphthylacetic acid (187.4 mg, 1.0 mmol) was suspended in DCM (4 mL) and placed in an ice bath. Thionyl chloride (365.5 pL, 5.0 mmol) was then added to the mixture, and the reaction mixture was allowed stir at 0 °C for 1 h. The reaction mixture was concentrated in vacuo and carried forward to the next step without further purification.
	With thionyl chloride; N,N-dimethyl-formamide In dichloromethane at 85℃; Inert atmosphere; Schlenk technique;

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[56]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - US2021/78940, 2021, A1 Location in patent: Paragraph 0264
[57]Roy, Sourav; Kumar, Gourav; Chatterjee, Indranil [Organic Letters, 2021, vol. 23, # 17, p. 6709 - 6713]
[58]Amin, Sk. Abdul; Trivedi, Prakruti; Adhikari, Nilanjan; Routholla, Ganesh; Vijayasarathi, Dhanya; Das, Sanjib; Ghosh, Balaram; Jha, Tarun [New Journal of Chemistry, 2021, vol. 45, # 37, p. 17149 - 17162]
[59]Chen, Jingyun; Chen, Shufang; Jiang, Jun; Lu, Qianqian; Shi, Liyang; Xu, Zekun; Yimei, Zhao [Journal of Organometallic Chemistry, 2022, vol. 957]
[60]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - US2022/9880, 2022, A1
[61]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - US2022/9880, 2022, A1
[62]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - US2022/9880, 2022, A1 Location in patent: Paragraph 0201; 0208; 0216; 0223; 0225
[63]Current Patent Assignee: DANA-FARBER CANCER INSTITUTE - WO2022/35805, 2022, A1 Location in patent: Paragraph 00195
[64]Current Patent Assignee: DANA-FARBER CANCER INSTITUTE - WO2022/35805, 2022, A1 Location in patent: Paragraph 00195
[65]Chen, Tieqiao; Huang, Tianzeng; Liu, Long; Szostak, Michal; Wang, Qun; Zuo, Dongxu [Angewandte Chemie - International Edition, 2022, vol. 61, # 24][Angew. Chem., 2022, vol. 134, # 24]

2
[ 37859-25-9 ]
[ 67198-26-9 ]
N-((1S,2S)-2-Dimethylamino-cyclohexyl)-N-methyl-2-naphthalen-2-yl-acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In diethyl ether

Reference： [1]Current Patent Assignee: PFIZER INC - BE860726, 1978, A [Chem.Abstr., vol. 89, # 146631][Chem.Abstr., vol. 89, # 146631]

3
[ 37859-25-9 ]
[ 593-56-6 ]
[ 113519-26-9 ]

Yield	Reaction Conditions	Operation in experiment
92%	With sodium carbonate In water; benzene for 5h; Ambient temperature;

Reference： [1]Kawase, Masami; Kitamura, Takahiro; Kikugawa, Yasuo [Journal of Organic Chemistry, 1989, vol. 54, # 14, p. 3394 - 3403]

4
[ 37859-25-9 ]
[ 93515-29-8 ]
[ 100597-44-2 ]

Yield	Reaction Conditions	Operation in experiment
89.3%	With sodium hydroxide In diethyl ether; water at 0℃; for 1h;

Reference： [1]Ogawa; Yamada; Terada; et al. [Chemical and Pharmaceutical Bulletin, 1985, vol. 33, # 6, p. 2256 - 2265]

5
[ 37859-25-9 ]
[ 459870-39-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium azide In water; acetone at 0 - 5℃; for 0.5h;
	With sodium azide In water; acetone at 0℃;

Reference： [1]Shah, Shrenik K.; Dorn, Conrad P.; Finke, Paul E.; Hale, Jeffrey J.; Hagmann, William K.; et al. [Journal of Medicinal Chemistry, 1992, vol. 35, # 21, p. 3745 - 3754]
[2]Leathen, Matthew L.; Peterson, Emily A. [Tetrahedron Letters, 2010, vol. 51, # 21, p. 2888 - 2891]

6
[ 37859-25-9 ]
[ 123-08-0 ]
4-formylphenyl 2-naphthylacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With triethylamine In diethyl ether at 0 - 20℃;

Reference： [1]Graffner-Nordberg, Malin; Sjoedin, Karin; Tunek, Anders; Hallberg, Anders [Chemical and Pharmaceutical Bulletin, 1998, vol. 46, # 4, p. 591 - 601]

7
[ 37859-25-9 ]
[ 108-95-2 ]
phenyl 2-(naphthalen-2-yl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With triethylamine In diethyl ether at 0 - 20℃;

Reference： [1]Graffner-Nordberg, Malin; Sjoedin, Karin; Tunek, Anders; Hallberg, Anders [Chemical and Pharmaceutical Bulletin, 1998, vol. 46, # 4, p. 591 - 601]

8
[ 37859-25-9 ]
Phosphoric acid mono-[4-((S)-2-amino-2-{(S)-1-[3-(4-trifluoromethyl-benzyl)-[1,2,4]oxadiazol-5-yl]-ethylcarbamoyl}-ethyl)-phenyl] ester [ No CAS ]
Phosphoric acid mono-[4-((S)-2-(2-naphthalen-2-yl-acetylamino)-2-{(S)-1-[3-(4-trifluoromethyl-benzyl)-[1,2,4]oxadiazol-5-yl]-ethylcarbamoyl}-ethyl)-phenyl] ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0 - 20℃; for 0.75h;

Reference： [1]Vu, Chi B.; Corpuz, Evelyn G.; Merry, Taylor J.; Pradeepan, Selvaluxmi G.; Bartlett, Catherine; Bohacek, Regine S.; Botfield, Martyn C.; Eyermann, Charles J.; Lynch, Berkley A.; MacNeil, Ian A.; Ram, Mary K.; Van Schravendijk, Marie Rose; Violette, Shelia; Sawyer, Tomi K. [Journal of Medicinal Chemistry, 1999, vol. 42, # 20, p. 4088 - 4098]

9
[ 37859-25-9 ]
[ 7498-57-9 ]

Yield	Reaction Conditions	Operation in experiment
75%	Stage #1: 2-naphthylacetyl chloride With oxalyl dichloride In benzene at 21℃; for 6h; Stage #2: With 2,4-dinitrobenzenesulfonamide; triethylamine In tetrahydrofuran for 24h; Heating;
60.38 g	With sulfolane; SULFAMIDE In toluene at 95 - 105℃; for 4h; Inert atmosphere;	2-6 In another nitrogen-substituted reactor were added sulfamide (46.49 g) (1.2 mole ratio to 2-naphthylacetic acid), an inorganic additive (74.99 g) (1 weight ratio to 2-naphthylacetic acid), and sulfolane (263 mL) (3.5 volume ratio to 2-naphthylacetic acid), and the mixture was heated (preparation of reaction starting material 2). The reaction starting material 1 containing 2-naphthylacetyl chloride was added dropwise to the reaction starting material 2 at 95° C.-105° over 18 min. The instrument used for preparing the reaction starting material 1 was washed with toluene (7.5 mL) (0.1 volume ratio to 2-naphthylacetic acid), the obtained solution was further added to the reaction starting material 2, and the mixture was reacted at 95° C.-105° C. for 4 hr. The reaction mixture was analyzed by HPLC, and the disappearance of the starting materials was confirmed. Then, the mixture was cooled to 20° C.-30° C., water (300 mL) (4 volume ratio to 2-naphthylacetic acid) and toluene (300 mL) (4 volume ratio to 2-naphthylacetic acid) were added, the mixture was stirred, and the aqueous layer was discarded. The remaining organic layer was washed with 10 wt % potassium carbonate aqueous solution (225.08 g) (3 weight ratio to 2-naphthylacetic acid) and water (150 mL) (2 volume ratio to 2-naphthylacetic acid). The obtained organic layer was concentrated, methanol (525 mL) (7 volume ratio to 2-naphthylacetic acid) was added to the concentrated residue, and the mixture was concentrated again. Furthermore, methanol was added to the obtained concentrated residue to adjust the liquid amount to 525 mL. Activated carbon (1.52 g) (0.02 weight ratio to 2-naphthylacetic acid) was added, and the mixture was stirred at 50° C.-60° C. and filtered. The obtained filtration residue was washed with methanol (75 mL) (1 volume ratio to 2-naphthylacetic acid). The obtained filtrate and washing solution were cooled to 5° C.-15° C., water (300 mL) (4 volume ratio to 2-naphthylacetic acid) was added, and the mixture was stirred. The precipitated 2-naphthylacetonitrile was collected by filtration, and the obtained wet crystals were dried to obtain 2-naphthylacetonitrile (60.38 g) (purity 99.85 area %) as a solid.

Reference： [1]Huber, Vincent J.; Bartsch, Richard A. [Tetrahedron, 1998, vol. 54, # 32, p. 9281 - 9288]
[2]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - US2022/9880, 2022, A1 Location in patent: Paragraph 0202-0204; 0209-0212; 0217-0220; 0224; 0226

10
[ 37859-25-9 ]
[ 21306-21-8 ]
(R)-2-chloro-3-(2-naphthyl)acetic acid pentachlorophenyl ester [ No CAS ]
(S)-2-chloro-3-(2-naphthyl)acetic acid pentachlorophenyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-naphthylacetyl chloride With resin-bound; O-benzoylquinine; 2-tert-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diazaphosphorine In tetrahydrofuran at -78℃; for 0.0666667h; Stage #2: 2,2,3,4,5,6-hexachloro-cyclohexa-2,4-dien-1-one In tetrahydrofuran at -78 - 25℃; for 4h; Title compound not separated from byproducts;

Reference： [1]France, Stefan; Wack, Harald; Taggi, Andrew E.; Hafez, Ahmed M.; Wagerle, Ty R.; Shah, Meha H.; Dusich, Crystal L.; Lectka, Thomas [Journal of the American Chemical Society, 2004, vol. 126, # 13, p. 4245 - 4255]

11
[ 37859-25-9 ]
[ 20244-61-5 ]
(R)-Bromo-naphthalen-2-yl-acetic acid 2,4,6-tribromo-phenyl ester [ No CAS ]
(S)-2-bromo-2-(2-naphthyl)acetic acid (2,4,6-tribromophenyl) ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-naphthylacetyl chloride With benzoylquinine; potassium carbonate In toluene at -78℃; for 12h; Stage #2: 2,4,4,6-Tetrabromo-2,5-cyclohexadien-1-one In toluene at -78 - 20℃; for 12h; Further stages.;

Reference： [1]Hafez, Ahmed M.; Taggi, Andrew E.; Wack, Harald; Esterbrook, Julie; Lectka, Thomas [Organic Letters, 2001, vol. 3, # 13, p. 2049 - 2051]

12
[ 37859-25-9 ]
[ 1775-95-7 ]
[ 265648-39-3 ]

Yield	Reaction Conditions	Operation in experiment
67%	In toluene for 2h; Heating;
	In 1,4-dioxane; toluene for 2h; Heating;

Reference： [1]Sakowski; Böhm; Sattler; Dahse; Schlitzer [Journal of Medicinal Chemistry, 2001, vol. 44, # 18, p. 2886 - 2899]
[2]Wiesner, Jochen; Kettler, Katja; Sakowski, Jacek; Ortmann, Regina; Jomaa, Hassan; Schlitzer, Martin [Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 3, p. 361 - 363]

13
[ 37859-25-9 ]
[ 107-95-9 ]
N-2-napthtylacetyl-β-alanine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With potassium hydrogencarbonate In acetone at 0 - 20℃; for 2h;

Reference： [1]Schlitzer; Rodriguez; Kador [Journal of Pharmacy and Pharmacology, 2001, vol. 53, # 6, p. 831 - 839]

14
[ 37859-25-9 ]
[ 25900-61-2 ]
N-methyl-3-(2-naphthalen-2-yl-acetylamino)-benzamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 4468 - 4474

15
[ 37859-25-9 ]
[ 108-91-8 ]
N-cyclohexyl-2-naphthalen-2-yl-acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88 mg	With triethylamine In dichloromethane at 25℃; for 20h;

Reference： [1]Tarzia, Giorgio; Duranti, Andrea; Tontini, Andrea; Piersanti, Giovanni; Mor, Marco; Rivara, Silvia; Plazzi, Pier Vincenzo; Park, Chris; Kathuria, Satish; Piomelli, Daniele [Journal of Medicinal Chemistry, 2003, vol. 46, # 12, p. 2352 - 2360]

16
[ 37859-25-9 ]
[ 27906-91-8 ]
[ 676566-00-0 ]

Yield	Reaction Conditions	Operation in experiment
83%	With pyridine In dichloromethane at 20℃;

Reference： [1]Šukalović; Roglić; Husinec; Kostić-Rajačić; Andrić; Šoškić, Vukić [Archiv der Pharmazie, 2003, vol. 336, # 11, p. 514 - 522]

17
[ 37859-25-9 ]
[ 142-84-7 ]
[ 676565-98-3 ]

Yield	Reaction Conditions	Operation in experiment
89%	With pyridine In dichloromethane at 20℃;

Reference： [1]Šukalović; Roglić; Husinec; Kostić-Rajačić; Andrić; Šoškić, Vukić [Archiv der Pharmazie, 2003, vol. 336, # 11, p. 514 - 522]

18
[ 37859-25-9 ]
[ 100-68-5 ]
[ 708276-20-4 ]

Yield	Reaction Conditions	Operation in experiment
90%	With aluminium trichloride In dichloromethane at 20℃; for 2.5h;

Reference： [1]Caturla, Francisco; Jiménez, Juan-Miguel; Godessart, Núria; Amat, Mercè; Cárdenas, Alvaro; Soca, Lídia; Beleta, Jordi; Ryder, Hamish; Crespo, María I. [Journal of Medicinal Chemistry, 2004, vol. 47, # 15, p. 3874 - 3886]

19
[ 37859-25-9 ]
[ 5717-37-3 ]
2-methyl-4-naphthalen-2-yl-buta-2,3-dienoic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With triethylamine In dichloromethane at 0 - 20℃;
	With triethylamine In dichloromethane at 20℃;	4.3 Typical procedure for the preparation of 2,3-allenoic acids (1) General procedure: A mixture of ethyl 2-(triphenylphosphoranylidene) propanoate (7.25g, 20mmol) and Et3N (2.03g, 20mmol) in DCM (100mL) was stirred at 0°C for 20min. Then, a solution of 2-arylacetyl chloride (24mmol) in DCM (40mL) was added dropwise and the reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with EtOAc, and washed with saturated aqueous NaCl solution. The combined organic layers were dried with Na2SO4, filtered, and the solvent was removed under reduced pressure. The resulting crude product was purified by flash chromatography on silica gel to give the corresponding 2,3-allenoates. To a round-bottom flask, 2,3-allenoate (5mmol), EtOH (15mL), H2O (15mL), and NaOH (0.3g, 7.5mmol) were added sequentially and the resulting solution was heated to reflux. After 2h, the reaction mixture was diluted with EtOAc, and washed with saturated aqueous NaHCO3 solution. The aqueous layer was separated, acidified to pH 2.0 by addition of HCl (1N), and extracted with DCM. The combined organic layers were dried with Na2SO4, filtered, and the solvent was removed under reduced pressure. The resulting crude product was purified by flash chromatography on silica gel to give the desired 2,3-allenoic acid.

Reference： [1]Nanayakkara, Perli; Alper, Howard [Journal of Organic Chemistry, 2004, vol. 69, # 14, p. 4686 - 4691]
[2]Huang, Yangen; Liu, Shuai; Qing, Feng-Ling; Xu, Xiu-Hua; Zhu, Yao-Yao [Journal of Fluorine Chemistry, 2022, vol. 257-258]

20
[ 398495-65-3 ]
[ 37859-25-9 ]
3-(2-naphthalen-2-yl-acetylamino)-4,6-dihydro-pyrrolo[3,4-c]pyrazole-1,5-dicarboxylic acid 5-tert-butyl ester 1-ethyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 1084 - 1090

21
[ 766514-64-1 ]
[ 37859-25-9 ]
[ 766514-66-3 ]

Yield	Reaction Conditions	Operation in experiment
43%	With triethylamine In dichloromethane at 20℃; for 2h;

Reference： [1]Venturi, Francesca; Venturi, Chiara; Liguori, Francesca; Cacciarini, Martina; Montalbano, Monica; Nativi, Cristina [Journal of Organic Chemistry, 2004, vol. 69, # 18, p. 6153 - 6155]

22
[ 37859-25-9 ]
2-naphthylketene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With basic resin BEMP In tetrahydrofuran at -78℃; for 0.0666667h;

Reference： [1]Wack; Taggi; Hafez; Drury III; Lectka [Journal of the American Chemical Society, 2001, vol. 123, # 7, p. 1531 - 1532]

23
[ 37859-25-9 ]
[ 3213-28-3 ]
[ 917086-43-2 ]

Yield	Reaction Conditions	Operation in experiment
41%	With triethylamine In ethyl acetate at 20℃; for 1h;

Reference： [1]Graulich, Amaury; Scuvée-Moreau, Jacqueline; Alleva, Livia; Lamy, Cédric; Waroux, Olivier; Seutin, Vincent; Liégeois, Jean-François [Journal of Medicinal Chemistry, 2006, vol. 49, # 24, p. 7208 - 7214]

24
[ 37859-25-9 ]
[ 693-57-2 ]
[ 905557-74-6 ]

Yield	Reaction Conditions	Operation in experiment
81%	With potassium hydroxide In methanol; water at 20℃; for 1h;
81%	With potassium hydroxide In methanol at 20℃; for 1h;	(i) 12-N-(2naphthylacetyl)aminododecanoic acid. To a solutionof 12-N-aminododecanoic acid (1.000 g, 4.64 mmol) in 20 mL of1 M methanolic KOH was added 2-naphthylacetyl chloride (1.424 g,7 mmol) in 20 mL aq. CH3OH (1:1), followed by stirring at roomtemperature for 1 h, whereupon a cloudy pale yellow suspensionformed. To the reaction mixture was added 100 mL CHCl3, and itwas acidified by addition of 1 M HCl to pH 4. The organic layerwas extracted and evaporated, and the residue was then treatedwith CH3OH (5 mL×20 mL). The combined methanol solution wasevaporated to give a light yellow residue that was purified on silicagel column using CHCl3-MeOH (9:1) as eluent. The fractionsof the product were combined, the solvent was evaporated, andthe residue was freeze-dried from benzene to give a light yellowpowder (1.432 g, 81%). (ii) PC-1. To a solution of compound11 (0.500 g, 0.812 mmol) in 15 mL CHCl3 were added 12-N-(2-naphthylacetyl)-aminododecanoic acid (1.560 g, 4.06 mmol) andDMAP (0.500 g, 4.06 mmol), followed by 1.5 g glass beads (Rossetoand Hajdu, 2005), and DCC (0.838 g, 4.06 mmol) in 5 mL CHCl3dropwise. The reaction mixture was sonicated for 5 h at 25 C. TheDCC-urea precipitate, and the glass beads were filtered, and the solventwas evaporated. The residue was dissolved in CHCl3-CH3OH(65:45), and loaded on a silica gel column for chromatography,first with CHCl3-CH3OH (65:25) to elute the impurities, followedby CHCl3-CH3OH-H2O (65:25:4) to elute the product. The fractions of the product were combined, the solvent was evaporated, andthe residue was freeze-dried from benzene to give pure PC-1 as awhite powder (0.450 g, 56.2%). IR (CHCl3): 1738, 1731, 1721, 1716,1660, 1620, 1603 cm-1; 1H NMR (CDCl3, 200 MHz) 1.12-1.78(br m, 34H), 2.25-2.45 (m, 4H), 2.38 (s, 3H), 2.94-3.20 (m, 4H),3.33 (s, 9H), 3.60-4.47 (br m, 10H), 5.05-5.25 (d, 1H), 6.15 (s, 1H),7.10 (d, 2H), 7.37 (d, 1H), 7.44 (d, 1H), 7.51 (t, 2H), 7.72 (s, 1H),7.84 (m, 3H); 13C NMR (CDCl3, 200 MHz) 18.72, 24.63, 24.70,25.01, 26.54, 28.32, 28.82, 29.01, 29.01,29.24, 29.24, 29.34, 29.34,29.46, 29.46, 29.52, 29.52, 29.61, 29.81, 32.30, 33.85, 34.28, 39.56,43.10, 54.32 [4C, CH2-N(CH3)3], 60.60, 66.02, 72.23, 113.87, 113.87,117.10, 123.17, 124.63, 124.95, 125.70, 126.95, 126.95, 127.59,127.59, 127.59, 131.60, 133.51, 135.20, 143.94, 152.36, 154.08,160.94, 169.50,173.65, 177.22; Anal. Calcd for C53H77N2O11PS·3.5H2O, C 60.95, H 8.05, N 2.68; Found: C 60.92, H 7.48, N 2.72; MS MH+(C53H77N2O11PSH+) Calcd: 981.5036; Found: 981.5059; Rf (CHCl3-CH3OH-H2O 65:25:4) = 0.41; []D25: +5.9 (c 1.06, CHCl3-MeOH4:1).

Reference： [1]Rosseto, Renato; Bibak, Niloufar; DeOcampo, Rosemarie; Shah, Trishul; Gabrielian, Ara; Hajdu, Joseph [Journal of Organic Chemistry, 2007, vol. 72, # 5, p. 1691 - 1698]
[2]Wang, Manlin; Pinnamaraju, Susmitha; Ranganathan, Radha; Hajdu, Joseph [Chemistry and Physics of Lipids, 2013, vol. 172-173, p. 78 - 85]

25
[ 37859-25-9 ]
[ 75-65-0 ]
[ 93579-03-4 ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane for 2.5h;	9.A To a solution of 5.0 g (26.9 rnmol) of 2-napthylacetic acid in 75 mL of dichloroniethane was added 2.60 mL (29.5 mmol) of oxalyl chloride followed by 0.20 mL (2.7 mmol) of N,N-dimethylformamide. The resulting solution was stirred at ambient temperature for 1 h and then all volatiles were removed in vacuo. The resulting residue was dissolved in 15 mL of dichloromethane and 15 mL of 2-methyl-2-propanol, and the resulting solution was stirred for 2.5 h. All volatiles were removed in vacuo and the crude residue was purified on a Biotage purification apparatus (silica gel, 7% ethyl acetate in hexanes) to afford the title compound as a colorless oil. LC/MS 243.1 (M+l).

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2007/120688, 2007, A2 Location in patent: Page/Page column 81

26
[ 37859-25-9 ]
[ 265648-40-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: toluene; dioxane / 2 h / Heating 2: SnCl₂*2H₂O / ethyl acetate / 2 h / Heating
	Multi-step reaction with 2 steps 1: 67 percent / toluene / 2 h / Heating 2: 98 percent / SnCl₂*2H₂O / ethyl acetate / 2 h / Heating

Reference： [1]Wiesner, Jochen; Kettler, Katja; Sakowski, Jacek; Ortmann, Regina; Jomaa, Hassan; Schlitzer, Martin [Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 3, p. 361 - 363]
[2]Sakowski; Böhm; Sattler; Dahse; Schlitzer [Journal of Medicinal Chemistry, 2001, vol. 44, # 18, p. 2886 - 2899]

27
[ 37859-25-9 ]
(R)-2-chloro-3-(2-naphthyl)acetic acid pentachlorophenyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: basic resin BEMP / benzoylquinine / tetrahydrofuran / 0.07 h / -78 °C 2: benzoylquinine / tetrahydrofuran / -78 - 20 °C

Reference： [1]Wack; Taggi; Hafez; Drury III; Lectka [Journal of the American Chemical Society, 2001, vol. 123, # 7, p. 1531 - 1532]

28
[ 37859-25-9 ]
(S)-2-chloro-3-(2-naphthyl)acetic acid pentachlorophenyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: basic resin BEMP / benzoylquinine / tetrahydrofuran / 0.07 h / -78 °C 2: benzoylquinine / tetrahydrofuran / -78 - 20 °C

Reference： [1]Wack; Taggi; Hafez; Drury III; Lectka [Journal of the American Chemical Society, 2001, vol. 123, # 7, p. 1531 - 1532]

29
[ 37859-25-9 ]
[ 6247-10-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 92 percent / sodium carbonate / H₂O; benzene / 5 h / Ambient temperature 2: 95 percent / tert-butyl hypochlorite / CH₂Cl₂ / 0.33 h / 0 °C 3: 69 percent / Ag₂CO₃, trifluoroacetic acid / 0.5 h / 0 °C 4: 87 percent / H₂ / 10percent Pd/C / methanol

Reference： [1]Kawase, Masami; Kitamura, Takahiro; Kikugawa, Yasuo [Journal of Organic Chemistry, 1989, vol. 54, # 14, p. 3394 - 3403]

30
[ 37859-25-9 ]
1,3-dihydro-2H-benz<e>indol-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 92 percent / sodium carbonate / H₂O; benzene / 5 h / Ambient temperature 2: 95 percent / tert-butyl hypochlorite / CH₂Cl₂ / 0.33 h / 0 °C 3: 69 percent / Ag₂CO₃, trifluoroacetic acid / 0.5 h / 0 °C 4: 84 percent / H₂ / 10percent Pd/C / methanol

Reference： [1]Kawase, Masami; Kitamura, Takahiro; Kikugawa, Yasuo [Journal of Organic Chemistry, 1989, vol. 54, # 14, p. 3394 - 3403]

31
[ 37859-25-9 ]
[ 719310-32-4 ]
4-(2-naphthalen-2-yl-1-oxoethyl)-3,4-dihydro-2H-benzo[1,4]oxazine-6-carbaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With isocyanate resin; triethylamine In 1,2-dichloro-ethane at 20℃; for 29h;	16 Intermediate 16: 4- (2-NAPHTHALEN-2-YL-2OXO-ETHYL)-3, 4-dihydro-2H- benzo [1, 4] oxazine-6-carbaldehyde Intermediate 16: 4- (2-NAPHTHALEN-2-YL-2OXO-ETHYL)-3, 4-dihydro-2H- benzo [1, 4] oxazine-6-carbaldehyde. To a solution of 1,2 dichloroethane (3 ml) and Intermediate 5 (0. 049 g, 0.300 mmol) was added triethylamine (0.054 ml, 0.390 mmol) followed by 2-naphthylacetyl chloride (0.068 g, 0.333 mmol). The reaction was stirred at room temperature for 24 hours. Isocyanate resin was added to scavenge excess Intermediate 5. The reaction was stirred for an additional 5 hours. Dichloromethane (2 ml) and saturated sodium bicarbonate (1 ml) were added to the reaction mixture and stirred for 10 minutes. The reaction mixture was filtered through a filter containing diatomaceous earth. The solvent was removed under reduced pressure to obtain the title product. MS: M++1=332. 1 Da.

Reference： [1]Current Patent Assignee: PFIZER INC - WO2004/56820, 2004, A1 Location in patent: Page 43-44

32
[ 37859-25-9 ]
[ 561030-69-1 ]
[ 561030-71-5 ]

Yield	Reaction Conditions	Operation in experiment
70%	With triethylamine In tetrahydrofuran at 0 - 20℃; for 16h;	3.1 1) 3'-[1-{N-(1-benzylpiperidin-4-yl)-N-(2-naphthylacetyl)amino}ethyl][1,1'-biphenyl]-2-carboxylic acid ethyl ester To a solution of the compound obtained in Reference Example 2 (3.81 g) and triethylamine (2.61 g) in THF (100 ml) was added a solution of 2-naphthylacetyl chloride (5.28 g) in THF (30 ml) under ice-cooling, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with saturated sodium bicarbonate solution (200 ml) and extracted with ethyl acetate (150 ml) twice. The extracted solutions were combined, washed with saturated brine, dried with magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography to give the title compound as a colorless amorphous substance (3.69 g, 70%).

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP1466904, 2004, A1 Location in patent: Page 36

33
[ 37859-25-9 ]
[ 561030-73-7 ]
N-(2-aminoethyl)-3'-[1-{N-(1-benzylpiperidin-4-yl)-N-(2-naphthylacetyl)amino}ethyl][1,1'-biphenyl]-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In tetrahydrofuran at 0 - 20℃; for 4h;	1 To a solution of the compound obtained in Reference Example 5 (70 mg) and triethylamine (38 mg) in THF (5 ml) was added a solution of 2-naphthylacetylchloride (77 mg) in THF (1 ml) under ice-cooling, and the mixture was stirred at room temperature for 4 hours. The reaction mixture was diluted with saturated sodium bicarbonate solution (100 ml) and extracted with ethyl acetate (50 ml) twice. The extracted solutions were combined, washed with saturated brine, dried with magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography to give a colorless amorphous substance (40 mg). To a solution of this amorphous substance (30 mg) in ethyl acetate (3 ml) was added a solution of 4 N hydrochloric acid in ethyl acetate (3 ml), and the mixture was stirred for 2 hours at room temperature. The reaction mixture was concentrated under reduced pressure, and crystallized from methanol-diethyl ether to give the title compound as a white powder (22 mg). 1H-NMR (CD3OD) δ: 1.17 (1H, br), 1.52 (3H, d), 1.80 (1H, d), 2.70-2.76 (4H, m), 2.98 (2H, t), 3.05-3.30 (3H, m), 3.41 (2H, t), 4.13(2H, s), 4.24(2H, br), 5.46 (1H, q), 7.10(1H, br), 7.13(1H, s), 7.40-7.57(14H, m), 7.78-7.86(4H, m). FAB-MS m/e: 625.4 (MH+). Elemental Analysis (Molecular formula C41H44N4O2·2HCl·1.4H2O) : Calcd. C: 68.12; H: 6.80; N: 7.75; Cl: 9.81. Found C: 67.93; H: 6.87; N: 7.71; Cl: 9.68.

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - EP1466904, 2004, A1 Location in patent: Page 41

34
[ 37859-25-9 ]
[ 69097-20-7 ]
1-hydroxy-3-[2]naphthyl-acetone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-naphthylacetyl chloride; tris(trimethylsilyloxy)ethylene at 90℃; for 5h; Stage #2: With hydrogenchloride In 1,3-dioxane; water at 90℃; for 0.166667h;	17.B Step B: 1-Hydroxy-3-(2-naphthyl)acetone At ambient temperature, under a stream of argon, 71.45 mmol of tris(trimethylsilyloxy)ethylene are slowly added to 28.58 mmol of (naphth-2-yl)acetyl chloride (obtained in Step A). After stirring for 5 hours at 90° C., the mixture is cooled and then a mixture of 12 ml of 0.6M hydrochloric acid and 30 ml of dioxane is slowly added. The reaction mixture is heated at 90° C. for 10 minutes and then cooled and extracted several times with diethyl ether. The organic phases are combined and washed in succession with a saturated aqueous solution of sodium hydrogen carbonate and a saturated aqueous solution of sodium chloride. The organic phase is dried over sodium sulphate, filtered and concentrated using a rotary evaporator. The residue obtained is chromatographed on silica gel using as eluant an ethyl acetate/hexane mixture in the proportions 6/4. The title product is obtained after recrystallisation from hexane. Melting point: 109-110° C.

Reference： [1]Current Patent Assignee: SERVIER MONDE - US2005/85644, 2005, A1 Location in patent: Page/Page column 6

35
[ 37859-25-9 ]
[ 168898-30-4 ]
(3ARS,4RS,5RS,7ARS)-7,7-diphenyl-4-(2-methoxyphenyl)-2-[(2-naphthyl)acetyl]perhydro-4,5-isoindolediol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; N-ethyl-N,N-diisopropylamine In dichloromethane; di-isopropyl ether; water; ethyl acetate; isopropyl alcohol	A.R.P.R.106891 Example A RPR106891 Example A RPR106891 To a solution of 0.42 g of (3aRS,4RS,5RS,7aRS)-7,7-diphenyl-4-(2-methoxyphenyl)perhydro-4,5-isoindolediol in 10 cm3 of dichloromethane is added 0.21 cm3 of diisopropylethylamine, followed by 0.23 g of 2-naphthylacetyl chloride in 5.5 cm3 of dichloromethane. After stirring at room temperature for 1 hour, 25 cm3 of water are added. The organic phase is separated off after settling, dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The residue is taken up in 50 cm3 of ethyl acetate, 3 cm3 of 1N aqueous hydrochloric acid and 40 cm3 of water. The organic phase is separated off after settling, dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The solid obtained is crystallized a first time in 5 cm3 of 2-propanol and then a second time in 5 cm3 of isopropyl ether. 0.3 g of (3aRS,4RS,5RS,7aRS)-7,7-diphenyl-4-(2-methoxyphenyl)-2-[(2-naphthyl)acetyl]perhydro-4,5-isoindolediol is obtained, melting at 188°-190° C.

Reference： [1]Current Patent Assignee: SANOFI - US5631279, 1997, A

36
[ 37859-25-9 ]
[ 153846-59-4 ]
[ 877379-17-4 ]

Yield	Reaction Conditions	Operation in experiment
87%	With triethylamine In dichloromethane at 20℃; for 16h;	14.2 Triethylamine (2.0 mL, 14.3 mmol) in 15 mL of methylene chloride was added under nitrogen dropwise over 2 h to a mixture of 2-(6-methoxy-naphthalen-2-yl)-2-oxo-ethyl-ammonium; chloride (1.58 g, 7.33 mmol), prepared in step 3 of Example 1 and naphthalen-2-yl-acetyl chloride (1.5 g, 7.33 mmol), prepared in the previous step, in 55 mL of methylene chloride at room temperature. After the addition the reaction was stirred at room temperature for 16 h (overnight). The reaction was diluted with methylene chloride, extracted twice with IN HC1, dried (MgS04), filtered and the solvent removed under reduced pressure to give 2.48 g of an orange solid. Purification of the solid on a Biotage KP-SIL 60 A 40+M 100 g column using hexane-ethyl acetate as the eluent gave N-[2-(7-methoxy-naphthalen-2yi)-2-oxo-ethyl]-2-naphthalen-2-yl-acetamide (1.54 g 87%) as an orange solid, mp 169-173°C. Elemental Analysis for C25H21NO3 Calc'd: C, 78.31; H, 5.52; N, 3.65. Found: C, 80.02; H, 5.64; N, 3.50.

Reference： [1]Current Patent Assignee: PFIZER INC - WO2006/23865, 2006, A1 Location in patent: Page/Page column 49

37
[ 37859-25-9 ]
[ 3846-71-7 ]
2-[2-(1-naphthylacetoxy)-3,5-di(tert-butyl)-phenyl]-benzotriazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dichloromethane;	Example C - Esterification with acid chloride 0.12 mol of triethylamine is added to a solution of 0.08 mol of 2-[2-hydroxy-3,5-di(tert-butyl)-phenyl]-benzotriazole in 150 ml of methylene chloride. To this solution is slowly added dropwise at 10°-15° C., with stirring, a solution of 0.08 mol of 2-naphthylacetyl chloride in 50 ml of methylene chloride. The temperature is then allowed to rise to 20°-25° C., and the mixture is stirred for 6 hours at this temperature. The triethylammonium chloride which has precipitated is filtered off, and the filtrate is washed with water, dried over Na2 SO4 and concentrated by evaporation. The crystalline, reddish-coloured residue is recrystallized from hexane to thus obtain 2-[2-(1-naphthylacetoxy)-3,5-di(tert-butyl)-phenyl]-benzotriazole in the form of white crystals which melt at 150°-151° C. (compound No. 25). There are obtained in an analogous manner the following phenol esters of the general formula STR8

Reference： [1]Patent: US5030731,1991,A

38
[ 37859-25-9 ]
[ 60376-74-1 ]
Methyl 3-(2-naphthylacetamide)-4-phenoxy-5-N,N-dimethylaminomethyleneaminosulfonylbenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In 1,4-dioxane; acetone	a a) a) Methyl 3-(2-naphthylacetamide)-4-phenoxy-5-N,N -dimethylaminomethyleneaminosulfonylbenzoate STR9 A solution of 18.5 g (0.09 mole) of 2-naphthylacetyl chloride in 65 ml of acetone is added dropwise to a solution of 20 g (0.053 mol) of methyl 3-amino-4-phenoxy -5-N,N-dimethylaminomethyleneaminosulfonylbenzoate in 200 ml of dioxane and 7.3 ml (0.09 mole) of pyridine at 80° C. After stirring at 80° C. for two hours, the solution is cooled, introduced into ice-water and extracted with methylene chloride. The methylene chloride solution is dried over Na2 SO4. and then evaporated in vacuo, and the residue is recrystallized from methanol. Crystals of melting point 127°-128° C.

Reference： [1]Current Patent Assignee: SANOFI - US5145867, 1992, A

39
[ 37859-25-9 ]
[ 65040-68-8 ]
1-(2-naphthylacetyl)-4-(3-trifluoromethylphenyl)-1,2,3,6-tetrahydropyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane	7.a EXAMPLE 7 (a) By operating as described in Example 6(a), 7 g of 4-(3-trifluoromethylphenyl)-1,2,3,6-tetrahydropyridine are reacted with 6.15 g of 2-naphthylacetyl chloride in the presence of 4.15 g of triethylamine in methylene chloride to give 9 g of 1-(2-naphthylacetyl)-4-(3-trifluoromethylphenyl)-1,2,3,6-tetrahydropyridine; m.p. 125°-130° C.

Reference： [1]Current Patent Assignee: SANOFI - US4521428, 1985, A

40
[ 37859-25-9 ]
2-deoxy-2,2-difluoro-pentafuranos-1-ulose [ No CAS ]
2-deoxy-2,2-difluoro-D-erythro-pentofuranos-1-ulose-3,5-di-2-naphthylacetate [ No CAS ]
C₂₈H₂₀F₂O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In dichloromethane for 2h; Heating / reflux;	8 2-deoxy-2,2-difluoropentofuranos-l-ulose (0.82 g) and pyridine (0.85 ml) were mixed in dichloromethane (10 ml) and a solution of 2-naphthylacetyl chloride (obtained by reacting 2-naphthylacetic acid with oxalyl chloride) in dichloromethane (10 ml) was added dropwise. After refluxing for 2 hours, the mixture was cooled and washed with water (10 ml), IM HCl (10 ml), 5% NaHCO3 (10 ml), water (10 ml), and brine (10 ml). The organic phase was dried over Na2SO4, and concentrated by rotatory evaporator to obtain a residue which was chromatographed to obtain an oil of 2-deoxy-2,2-difluoro-D-erythro- pentofuranos-1 -ulose-3, 5-di-2-naphthylacetate, as a mixture of erythro and threo isomers.

Reference： [1]Current Patent Assignee: PERRIGO COMPANY PUBLIC LIMITED COMPANY; SK CAPITAL PARTNERS LP - WO2007/27564, 2007, A2 Location in patent: Page/Page column 23

41
[ 37859-25-9 ]
[ 14630-40-1 ]
[ 1013936-65-6 ]

Yield	Reaction Conditions	Operation in experiment
13%	In dichloromethane at 0℃; for 3h;
1.0776 g	With aluminum (III) chloride In dichloromethane at 0 - 20℃; Inert atmosphere;

Reference： [1]Yamauchi, Yoshihiro; Yuki, Masahiro; Tanabe, Yoshiaki; Miyake, Yoshihiro; Inada, Youichi; Uemura, Sakae; Nishibayashi, Yoshiaki [Journal of the American Chemical Society, 2008, vol. 130, # 10, p. 2908 - 2909]
[2]Wang, Hengbin; Denton, Justin R.; Davies, Huw M. L. [Organic Letters, 2011, vol. 13, # 16, p. 4316 - 4319]

42
[ 37859-25-9 ]
[ 108-98-5 ]
[ 335193-39-0 ]

Yield	Reaction Conditions	Operation in experiment
90%	With triethylamine In toluene

Reference： [1]Boettcher, Thomas; Sieber, Stephan A. [Angewandte Chemie - International Edition, 2008, vol. 47, # 24, p. 4600 - 4603]

43
[ 37859-25-9 ]
[ 616-38-6 ]
[ 105048-64-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride In mineral oil at 0 - 20℃; Inert atmosphere;

Reference： [1]Shintani, Ryo; Murakami, Masataka; Hayashi, Tamio [Organic Letters, 2009, vol. 11, # 2, p. 457 - 459]

44
[ 67-56-1 ]
[ 37859-25-9 ]
[ 1094608-44-2 ]

Yield	Reaction Conditions	Operation in experiment
63%	Stage #1: 2-naphthylacetyl chloride With o-benzoylquinidine; bis-triphenylphosphine-palladium(II) chloride; N-fluorobis(benzenesulfon)imide; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at -78℃; Inert atmosphere; Stage #2: methanol In tetrahydrofuran at -78 - 20℃; optical yield given as %ee;

Reference： [1]Paull, Daniel H.; Scerba, Michael T.; Alden-Danforth, Ethan; Widger, Leland R.; Lectka, Thomas [Journal of the American Chemical Society, 2008, vol. 130, # 51, p. 17260 - 17261]

45
[ 37859-25-9 ]
[ 159980-12-8 ]
[ 1186621-61-3 ]

Yield	Reaction Conditions	Operation in experiment
80%	With triethylamine In tetrahydrofuran for 18h; Reflux;

Reference： [1]Location in patent: experimental part Michielan, Lisa; Bolcato, Chiara; Federico, Stephanie; Cacciari, Barbara; Bacilieri, Magdalena; Klotz, Karl-Norbert; Kachler, Sonja; Pastorin, Giorgia; Cardin, Riccardo; Sperduti, Alessandro; Spalluto, Giampiero; Moro, Stefano [Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 14, p. 5259 - 5274]

46
[ 37859-25-9 ]
[ 159980-13-9 ]
[ 1186621-62-4 ]

Yield	Reaction Conditions	Operation in experiment
77%	With triethylamine In tetrahydrofuran for 18h; Reflux;

Reference： [1]Location in patent: experimental part Michielan, Lisa; Bolcato, Chiara; Federico, Stephanie; Cacciari, Barbara; Bacilieri, Magdalena; Klotz, Karl-Norbert; Kachler, Sonja; Pastorin, Giorgia; Cardin, Riccardo; Sperduti, Alessandro; Spalluto, Giampiero; Moro, Stefano [Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 14, p. 5259 - 5274]

47
[ 37859-25-9 ]
(1RS,4RS)-2,2-difluoro-4-[(4-pentylphenyl)amino]methyl}cyclohexyl acetate [ No CAS ]
(1RS,4RS)-2,2-difluoro-4-[(2-naphthylacetyl)(4-pentylphenyl)amino]methyl}cyclohexyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 24h; Inert atmosphere;

Reference： [1]Faeh, Christoph; Hardegger, Leo A.; Baitsch, Lukas; Schweizer, W. Bernd; Meyer, Solange; Bur, Daniel; Diederich, Francois [Organic and Biomolecular Chemistry, 2009, vol. 7, # 19, p. 3947 - 3957]

48
[ 37859-25-9 ]
(1SR,4RS)-2,2-difluoro-4-[(4-pentylphenyl)amino]methyl}cyclohexyl acetate [ No CAS ]
(1SR,4RS)-2,2-difluoro-4-[(2-naphthylacetyl)(4-pentylphenyl)amino]methyl}cyclohexyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 24h; Inert atmosphere;

Reference： [1]Faeh, Christoph; Hardegger, Leo A.; Baitsch, Lukas; Schweizer, W. Bernd; Meyer, Solange; Bur, Daniel; Diederich, Francois [Organic and Biomolecular Chemistry, 2009, vol. 7, # 19, p. 3947 - 3957]

49
[ 37859-25-9 ]
[ 1194818-29-5 ]
(1RS,4SR)-2,2-difluoro-4-[(2-naphthylacetyl)(4-pentylphenyl)amino]methyl}cyclopentyl acetate [ No CAS ]
(1SR,4SR)-2,2-difluoro-4-[(2-naphthylacetyl)(4-pentylphenyl)amino]methyl}cyclopentyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 40% 2: 42%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 5h; Inert atmosphere;

Reference： [1]Faeh, Christoph; Hardegger, Leo A.; Baitsch, Lukas; Schweizer, W. Bernd; Meyer, Solange; Bur, Daniel; Diederich, Francois [Organic and Biomolecular Chemistry, 2009, vol. 7, # 19, p. 3947 - 3957]

50
[ 37859-25-9 ]
(1SR,5RS)-2,2-difluoro-5-[(4-pentylphenyl)amino]cyclohexyl acetate [ No CAS ]
(1RS,5SR)-2,2-difluoro-5-[(2-naphthylacetyl)-(4-pentylphenyl)amino]cyclohexyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 16h; Inert atmosphere;

Reference： [1]Faeh, Christoph; Hardegger, Leo A.; Baitsch, Lukas; Schweizer, W. Bernd; Meyer, Solange; Bur, Daniel; Diederich, Francois [Organic and Biomolecular Chemistry, 2009, vol. 7, # 19, p. 3947 - 3957]

51
[ 37859-25-9 ]
(1SR,5SR)-2,2-difluoro-5-[(4-pentylphenyl)amino]cyclohexyl acetate [ No CAS ]
(1SR,5SR)-2,2-difluoro-5-[(2-naphthylacetyl)-(4-pentylphenyl)amino]cyclohexyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 16h; Inert atmosphere;

Reference： [1]Faeh, Christoph; Hardegger, Leo A.; Baitsch, Lukas; Schweizer, W. Bernd; Meyer, Solange; Bur, Daniel; Diederich, Francois [Organic and Biomolecular Chemistry, 2009, vol. 7, # 19, p. 3947 - 3957]

52
[ 37859-25-9 ]
[ 1194818-92-2 ]
[ 1194818-98-8 ]

Yield	Reaction Conditions	Operation in experiment
88%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 16h; Inert atmosphere;

Reference： [1]Faeh, Christoph; Hardegger, Leo A.; Baitsch, Lukas; Schweizer, W. Bernd; Meyer, Solange; Bur, Daniel; Diederich, Francois [Organic and Biomolecular Chemistry, 2009, vol. 7, # 19, p. 3947 - 3957]

53
[ 37859-25-9 ]
[ 1194818-95-5 ]
[ 1194819-01-6 ]

Yield	Reaction Conditions	Operation in experiment
75%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 16h; Inert atmosphere;

Reference： [1]Faeh, Christoph; Hardegger, Leo A.; Baitsch, Lukas; Schweizer, W. Bernd; Meyer, Solange; Bur, Daniel; Diederich, Francois [Organic and Biomolecular Chemistry, 2009, vol. 7, # 19, p. 3947 - 3957]

54
[ 37859-25-9 ]
[ 33228-44-3 ]
[ 1194818-01-3 ]

Yield	Reaction Conditions	Operation in experiment
8.1 g	With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 1h; Inert atmosphere;

Reference： [1]Location in patent: experimental part Faeh, Christoph; Hardegger, Leo A.; Baitsch, Lukas; Schweizer, W. Bernd; Meyer, Solange; Bur, Daniel; Diederich, Francois [Organic and Biomolecular Chemistry, 2009, vol. 7, # 19, p. 3947 - 3957]

55
[ 37859-25-9 ]
[ 1246923-62-5 ]
[ 1246923-63-6 ]

Yield	Reaction Conditions	Operation in experiment
70%	With triethylamine In dichloromethane at 22℃; for 16h; Inert atmosphere;

Reference： [1]Faeh, Christoph; Mathys, Roland; Hardegger, Leo A.; Meyer, Solange; Bur, Daniel; Diederich, Francois [European Journal of Organic Chemistry, 2010, # 24, p. 4617 - 4629]

56
[ 37859-25-9 ]
[ 62515-92-8 ]
C₂₆H₂₁NO₂ [ No CAS ]
C₃₈H₂₉NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 21% 2: 5%	Stage #1: 2-naphthylacetyl chloride With triethylamine In dichloromethane at -78℃; for 0.333333h; Inert atmosphere; Stage #2: N-p-methoxyphenyl-2,4,6-cycloheptatriene-1-imine In dichloromethane at -78 - 20℃; Inert atmosphere;

Reference： [1]Lage, Marta L.; Fernandez, Israel; Sierra, Miguel A.; Torres, M. Rosario [Organic Letters, 2011, vol. 13, # 11, p. 2892 - 2895]

57
[ 37859-25-9 ]
[ 6638-79-5 ]
N-methoxy-N-methyl-2-(naphthalen-2-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2.6984 g	With potassium carbonate In water; toluene at 0 - 20℃; Inert atmosphere;

Reference： [1]Wang, Hengbin; Denton, Justin R.; Davies, Huw M. L. [Organic Letters, 2011, vol. 13, # 16, p. 4316 - 4319]

58
[ 37859-25-9 ]
[ 90319-52-1 ]
(4R)-3-(naphthalen-2-ylacetyl)-4-phenyl-1,3-oxazolidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	Stage #1: (4R)-phenyl-2-oxazolidinone With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: 2-naphthylacetyl chloride In tetrahydrofuran; hexane at -78 - 20℃; for 6h; Inert atmosphere;
	Stage #1: (4R)-phenyl-2-oxazolidinone With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: 2-naphthylacetyl chloride In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere;

Reference： [1]Matousek, Vaclav; Togni, Antonio; Bizet, Vincent; Cahard, Dominique [Organic Letters, 2011, vol. 13, # 21, p. 5762 - 5765]
[2]Chachignon, Hélène; Kondrashov, Evgeniy V.; Cahard, Dominique [Advanced Synthesis and Catalysis, 2018, vol. 360, # 5, p. 965 - 971]

59
[ 37859-25-9 ]
[ 871130-18-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 36 h / Inert atmosphere; Heating; Neat (no solvent) 2: potassium hydroxide / water / Heating 3: 36 h 4: 6 h / 25 °C
	Multi-step reaction with 4 steps 1: 36 h / Inert atmosphere; Heating; Neat (no solvent) 2: potassium hydroxide / methanol; water / 15 h / Heating 3: 36 h 4: 6 h / 25 °C
	Multi-step reaction with 4 steps 1: 48 h / Inert atmosphere; Heating; Neat (no solvent) 2: potassium hydroxide / water / Heating 3: 36 h 4: 6 h / 25 °C

Multi-step reaction with 4 steps 1: 48 h / Inert atmosphere; Heating; Neat (no solvent) 2: potassium hydroxide / methanol; water / 15 h / Heating 3: 36 h 4: 6 h / 25 °C

Reference： [1]Ding, Zhensheng; Osminski, Wynter E. G.; Ren, Hong; Wulff, William D. [Organic process research and development, 2011, vol. 15, # 5, p. 1089 - 1107]
[2]Ding, Zhensheng; Osminski, Wynter E. G.; Ren, Hong; Wulff, William D. [Organic process research and development, 2011, vol. 15, # 5, p. 1089 - 1107]
[3]Ding, Zhensheng; Osminski, Wynter E. G.; Ren, Hong; Wulff, William D. [Organic process research and development, 2011, vol. 15, # 5, p. 1089 - 1107]
[4]Ding, Zhensheng; Osminski, Wynter E. G.; Ren, Hong; Wulff, William D. [Organic process research and development, 2011, vol. 15, # 5, p. 1089 - 1107]

60
[ 37859-25-9 ]
[ 200810-26-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 36 h / Inert atmosphere; Heating; Neat (no solvent) 2: potassium hydroxide / water / Heating 3: 36 h
	Multi-step reaction with 3 steps 1: 36 h / Inert atmosphere; Heating; Neat (no solvent) 2: potassium hydroxide / methanol; water / 15 h / Heating 3: 36 h
	Multi-step reaction with 3 steps 1: 48 h / Inert atmosphere; Heating; Neat (no solvent) 2: potassium hydroxide / water / Heating 3: 36 h

	Multi-step reaction with 3 steps 1: 48 h / Inert atmosphere; Heating; Neat (no solvent) 2: potassium hydroxide / methanol; water / 15 h / Heating 3: 36 h
	Multi-step reaction with 2 steps 1.1: 48 h / 190 °C 1.2: 1 h / 100 °C 2.1: air / mineral oil / 36 h / 170 °C

Reference： [1]Ding, Zhensheng; Osminski, Wynter E. G.; Ren, Hong; Wulff, William D. [Organic process research and development, 2011, vol. 15, # 5, p. 1089 - 1107]
[2]Ding, Zhensheng; Osminski, Wynter E. G.; Ren, Hong; Wulff, William D. [Organic process research and development, 2011, vol. 15, # 5, p. 1089 - 1107]
[3]Ding, Zhensheng; Osminski, Wynter E. G.; Ren, Hong; Wulff, William D. [Organic process research and development, 2011, vol. 15, # 5, p. 1089 - 1107]
[4]Ding, Zhensheng; Osminski, Wynter E. G.; Ren, Hong; Wulff, William D. [Organic process research and development, 2011, vol. 15, # 5, p. 1089 - 1107]
[5]Gupta, Anil K.; Zhang, Xin; Staples, Richard J.; Wulff, William D. [Catalysis science and technology, 2014, vol. 4, # 12, p. 4406 - 4415]

61
[ 37859-25-9 ]
(3S)-(+)-2,2'-diphenyl-(3,3'-biphenanthrene)-4,4'-diol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: 36 h / Inert atmosphere; Heating; Neat (no solvent) 2: potassium hydroxide / water / Heating 3: 36 h 4: 6 h / 25 °C 5: ethanol / Heating 6: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 0 - 25 °C / Inert atmosphere
	Multi-step reaction with 6 steps 1: 36 h / Inert atmosphere; Heating; Neat (no solvent) 2: potassium hydroxide / methanol; water / 15 h / Heating 3: 36 h 4: 6 h / 25 °C 5: ethanol / Heating 6: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 0 - 25 °C / Inert atmosphere
	Multi-step reaction with 6 steps 1: 48 h / Inert atmosphere; Heating; Neat (no solvent) 2: potassium hydroxide / water / Heating 3: 36 h 4: 6 h / 25 °C 5: ethanol / Heating 6: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 0 - 25 °C / Inert atmosphere

	Multi-step reaction with 6 steps 1: 48 h / Inert atmosphere; Heating; Neat (no solvent) 2: potassium hydroxide / methanol; water / 15 h / Heating 3: 36 h 4: 6 h / 25 °C 5: ethanol / Heating 6: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 0 - 25 °C / Inert atmosphere
	Multi-step reaction with 3 steps 1.1: 48 h / 190 °C 1.2: 1 h / 100 °C 2.1: air / mineral oil / 36 h / 170 °C 3.1: copper(II)-(-)-sparteine complex / methanol; dichloromethane / 6 h / 25 °C

Reference： [1]Ding, Zhensheng; Osminski, Wynter E. G.; Ren, Hong; Wulff, William D. [Organic process research and development, 2011, vol. 15, # 5, p. 1089 - 1107]
[2]Ding, Zhensheng; Osminski, Wynter E. G.; Ren, Hong; Wulff, William D. [Organic process research and development, 2011, vol. 15, # 5, p. 1089 - 1107]
[3]Ding, Zhensheng; Osminski, Wynter E. G.; Ren, Hong; Wulff, William D. [Organic process research and development, 2011, vol. 15, # 5, p. 1089 - 1107]
[4]Ding, Zhensheng; Osminski, Wynter E. G.; Ren, Hong; Wulff, William D. [Organic process research and development, 2011, vol. 15, # 5, p. 1089 - 1107]
[5]Gupta, Anil K.; Zhang, Xin; Staples, Richard J.; Wulff, William D. [Catalysis science and technology, 2014, vol. 4, # 12, p. 4406 - 4415]

62
[ 37859-25-9 ]
[ 100-02-7 ]
[ 250142-41-7 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In dichloromethane at 0 - 20℃;

Reference： [1]Hao, Lin; Du, Yu; Lv, Hui; Chen, Xingkuan; Jiang, Huishen; Shao, Yaling; Chi, Yonggui Robin [Organic Letters, 2012, vol. 14, # 8, p. 2154 - 2157]

63
[ 37859-25-9 ]
C₅H₄BrN₃S [ No CAS ]
[ 1279721-70-8 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-naphthylacetyl chloride; C₅H₄BrN₃S With triethylamine In ethyl acetate for 15h; Inert atmosphere; Stage #2: With ammonium chloride In water; ethyl acetate	83.6 3-Bromo-7-nitroimidazo[5,l-6][1,3]thiazole (120 mg, 0.50 mmol) and Platinum 3 wt % on activated carbon, doped with 0.6% Vanadium (160 mg, 0.03 mmol) were placed in a parr shaker vial that was covered with parafilm. Argon was introduced to the vial, and ethyl acetate (5 mL) was introduced via syringe. The vial was taken to the parr shaker and evacuated then backfilled with nitrogen (3x), then evacuated and backfilled with hydrogen (3x). The reaction was shaken under 50 psi hydrogen for 8 hours. It was then evacuated and backfilled with nitrogen (3x) and filtered through a celite plug, washing with ethyl acetate, to afford a cherry red solution. The solution was concentrated to ½ its original volume under reduced pressure (without using a water bath), and then immediately treated with naphthalen-2-ylacetyl chloride (120 mg, 0.60 mmol) and triethylamine (0.28 ml, 2.0 mmol). The resulting orange slurry stirred under a blanket of argon for 15 hours. The mixture was diluted with ethyl acetate and quenched with saturated aqueous ammonium chloride. The biphasic mixture was filtered and the solids collected to afford the title compound as a white powder. LRMS (APCI) calc'd for C,7I½BrNjOS [M+l , [M+3]+: 386.0, 388.0; Found: 385.7, 387.6. 1H NMR (500 MHz, d6-OUSO): δ 10.95 (s, 1 H), 7.98 (s, 1 H), 7.86 (m, 3 H), 7.80 (s, 1 H), 7.47 (m, 3 H), 7.27 (s, 1 H), 3.77 (s, 2 H).

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2011/37780, 2011, A1 Location in patent: Page/Page column 55; 57-58

64
[ 37859-25-9 ]
[ 1279721-78-6 ]
[ 1279721-80-0 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-naphthylacetyl chloride; ethyl 7-amino-3-(trifluoromethyl)imidazo[5,1-b][1,3]thiazole-2-carboxylate hydrochloride With N-ethyl-N,N-diisopropylamine In dichloromethane Stage #2: With sodium hydrogencarbonate In dichloromethane; water	85.4 Ethyl 7-amino-3-(trifluoromethyl)imidazo[5,l-&][1,3]thiazole-2-carboxylate hydrochloride (80 mg, 0.25 mmol) and diisopropylethyl amine (140 uL, 1.0 mmol) were taken up indichloromethane (1.0 mL). Naphthalen-2-ylacetyl chloride (62 mg, 0.30 mmol) in minimal dichloromethane was added dropwise and the reaction was allowed to stir for one hr. The reaction was then diluted with dichloromethane and transferred to a separatory funnel. The mixture was washed with saturated aqueous sodium bicarbonate, brine, dried with sodium sulfate, filtered, and concentrated under reduced pressure. The solid was then titurated with methanol and filtered to afford the title compound. LRMS (APCI) calc'd for C2iH16F3N303S [M+H]+: 448.4, Found: 447.9.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2011/37780, 2011, A1 Location in patent: Page/Page column 59; 61

65
[ 37859-25-9 ]
[ 2198-93-8 ]
[ 1431698-54-2 ]

Yield	Reaction Conditions	Operation in experiment
84.9%	With dmap; triethylamine In dichloromethane at 20℃; for 8h;

Reference： [1]Xu, Xiaojun; Cheng, Jingli; Zhou, Yong; Zhang, Chulong; Ou, Xiaoming; Su, Weike; Zhao, Jinhao; Zhu, Guonian [Chemistry and biodiversity, 2013, vol. 10, # 4, p. 600 - 611]

66
[ 37859-25-9 ]
C₁₃H₁₉N₅O₂S [ No CAS ]
N-[3-(1H-imidazol-1-yl)propyl]-2-[(2-methoxyethyl)(naphthalen-2-ylacetyl)amino]-1,3-thiazole-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In dichloromethane at 25℃; for 2h;	185 General procedure: Example 6B (0.2 g, 0.556 mmol) was dissolved in dichloromethane (2.7 ml) and pyridine (0.3 ml) and was treated dropwise with a solution of 3-methylbutanoyl chloride (0.102 ml, 0.835 mmol) in dichloromethane (0.5 ml). The reaction mixture was stirred at 25 °C for 2 hours, concentrated, and purified using reverse phase HPLC (Phenomenex Luna C8(2) 5 um ΙΟθΑ AXIA column (30mm x 75mm) run with a gradient of acetonitrile (A) and 0.1% trifluoroacetic acid in water (B), at a flow rate of 50mL/min (0-0.5 min 10% A, 0.5-7.0 min linear gradient 10-95% A, 7.0- 10.0 min 95% A, 10.0-12.0 min linear gradient 95- 10% A) to afford the title compound.

Reference： [1]Current Patent Assignee: ABBVIE INC - WO2013/170118, 2013, A1 Location in patent: Page/Page column 129

67
[ 37859-25-9 ]
[ 107466-55-7 ]
[ 1600530-05-9 ]

Yield	Reaction Conditions	Operation in experiment
65%	In tetrahydrofuran; pyridine at 20℃;	5.16 Acylation of anthranilic acid derivatives General procedure: Anthranilic acid derivative (6a-j, 1.0 equiv) was dissolved in THF (3 mL/mmol6a-j) and pyridine (3.0 equiv) was added. After a clear solution had formed, the respective acyl chloride (8a-p, 1.3 equiv) wasadded in THF (2 mL/mmol 6a-j). The reaction mixture was keptat room temperature for 4-8 h and the reaction progress was monitored by TLC. When anthranilic acid derivative (6a-j) was consumed, the reaction mixture was diluted with ethyl acetate,washed three times with 10% hydrochloric acid and dried over Na2SO4. Further purification was performed by column chromatography on silica.).

Reference： [1]Merk, Daniel; Gabler, Matthias; Gomez, Roberto Carrasco; Flesch, Daniel; Hanke, Thomas; Kaiser, Astrid; Lamers, Christina; Werz, Oliver; Schneider, Gisbert; Schubert-Zsilavecz, Manfred [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 8, p. 2447 - 2460]

68
[ 288-13-1 ]
[ 37859-25-9 ]
[ 1609077-15-7 ]

Yield	Reaction Conditions	Operation in experiment
21 mg	In dichloromethane at 0 - 20℃; for 3h; Inert atmosphere;	General Procedure D. General procedure: The appropriate carboxylic acid (1.0 equiv) was treated with oxalyl chloridie (1.1 equiv) in CH2Cl2 (0.5 M) at 0° C. The reaction mixture was stirred at room temperature for 1 h. The solvent was removed under N2 and the acid chloride was redissolved in anhydrous CH2Cl2 (0.5 M). The appropriate pyrazole (1.0 equiv) was dissolved in CH2Cl2 and cooled to 0° C. The acid chloride was added dropwise and the reaction mixture was stirred at room temperature for 3 h. The mixture was diluted withEtOAc, washed with saturated aqueous NaCl, and dried over Na2SO4. Evaporation under reduced pressure yielded the crude product that was purified by flash chromatography(SiO2).
	In dichloromethane at 0 - 20℃; for 3h; Inert atmosphere;	4.1.2. General procedure for pyrazole amide synthesis General procedure: The appropriate carboxylic acid (1.0 equiv) was treated with oxalylchloride (1.1 equiv) in CH2Cl2 (0.5 M) at 0 °C. The reaction mixture wasstirred at room temperature for 1 h. The solvent was removed under N2and the acid chloride (1 equiv) was dissolved in anhydrous CH2Cl2(0.5 M). The appropriate pyrazole (1.0 equiv) was dissolved in CH2Cl2(0.5 M) and cooled to 0 °C. The acid chloride (1 equiv) in CH2Cl2 (0.5 M) was added dropwise and the reaction mixture was stirred atroom temperature for 3 h. The mixture was diluted with EtOAc, washedwith saturated aqueous NaCl, and dried over Na2SO4. Evaporationunder reduced pressure yielded the crude product that was purified byflash chromatography (SiO2).

Reference： [1]Otrubova, Katerina; Srinivasan, Venkat; Boger, Dale L. [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 16, p. 3807 - 3813]
[2]Otrubova, Katerina; Chatterjee, Shreyosree; Ghimire, Srijana; Cravatt, Benjamin F.; Boger, Dale L. [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 8, p. 1693 - 1703]

69
[ 7554-65-6 ]
[ 37859-25-9 ]
[ 1622426-74-7 ]

Yield	Reaction Conditions	Operation in experiment
21 mg	In dichloromethane at 0 - 20℃; for 3h; Inert atmosphere;	General Procedure D. General procedure: The appropriate carboxylic acid (1.0 equiv) was treated with oxalyl chloridie (1.1 equiv) in CH2Cl2 (0.5 M) at 0° C. The reaction mixture was stirred at room temperature for 1 h. The solvent was removed under N2 and the acid chloride was redissolved in anhydrous CH2Cl2 (0.5 M). The appropriate pyrazole (1.0 equiv) was dissolved in CH2Cl2 and cooled to 0° C. The acid chloride was added dropwise and the reaction mixture was stirred at room temperature for 3 h. The mixture was diluted withEtOAc, washed with saturated aqueous NaCl, and dried over Na2SO4. Evaporation under reduced pressure yielded the crude product that was purified by flash chromatography(SiO2).
	In dichloromethane at 0 - 20℃; for 3h; Inert atmosphere;	4.1.2. General procedure for pyrazole amide synthesis General procedure: The appropriate carboxylic acid (1.0 equiv) was treated with oxalylchloride (1.1 equiv) in CH2Cl2 (0.5 M) at 0 °C. The reaction mixture wasstirred at room temperature for 1 h. The solvent was removed under N2and the acid chloride (1 equiv) was dissolved in anhydrous CH2Cl2(0.5 M). The appropriate pyrazole (1.0 equiv) was dissolved in CH2Cl2(0.5 M) and cooled to 0 °C. The acid chloride (1 equiv) in CH2Cl2 (0.5 M) was added dropwise and the reaction mixture was stirred atroom temperature for 3 h. The mixture was diluted with EtOAc, washedwith saturated aqueous NaCl, and dried over Na2SO4. Evaporationunder reduced pressure yielded the crude product that was purified byflash chromatography (SiO2).

Reference： [1]Otrubova, Katerina; Srinivasan, Venkat; Boger, Dale L. [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 16, p. 3807 - 3813]
[2]Otrubova, Katerina; Chatterjee, Shreyosree; Ghimire, Srijana; Cravatt, Benjamin F.; Boger, Dale L. [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 8, p. 1693 - 1703]

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+

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{[ 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) ]}	{[ 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. :	37859-25-9	MDL No. :	MFCD02180524
Formula :	C₁₂H₉ClO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	QEJGMKHQXSZCOS-UHFFFAOYSA-N
M.W :	204.65	Pubchem ID :	588115
Synonyms :

Num. heavy atoms :	14
Num. arom. heavy atoms :	10
Fraction Csp3 :	0.08
Num. rotatable bonds :	2
Num. H-bond acceptors :	1.0
Num. H-bond donors :	0.0
Molar Refractivity :	58.72
TPSA :	17.07 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-4.86 cm/s

[ CAS No. 37859-25-9 ]

Quality Control of [ 37859-25-9 ]

Related Doc. of [ 37859-25-9 ]

Product Details of [ 37859-25-9 ]

Calculated chemistry of [ 37859-25-9 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 37859-25-9 ]

Application In Synthesis of [ 37859-25-9 ]

[ 37859-25-9 ] Synthesis Path-Downstream 1~69

Related Functional Groups of
[ 37859-25-9 ]

Aryls

Chlorides

Acyl Chlorides

Precautionary Statements-General

Prevention

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Environmental hazards

Inquiry

Log Po/w (iLOGP) :	2.14
Log Po/w (XLOGP3) :	3.79
Log Po/w (WLOGP) :	3.15
Log Po/w (MLOGP) :	3.04
Log Po/w (SILICOS-IT) :	3.81
Consensus Log Po/w :	3.18

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

Log S (ESOL) :	-3.89
Solubility :	0.0262 mg/ml ; 0.000128 mol/l
Class :	Soluble
Log S (Ali) :	-3.84
Solubility :	0.0294 mg/ml ; 0.000144 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-5.05
Solubility :	0.00183 mg/ml ; 0.00000895 mol/l
Class :	Moderately soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	1.34

Signal Word:	Danger	Class:	8
Precautionary Statements:	P260-P264-P280-P301+P330+P331-P303+P361+P353-P304+P340-P305+P351+P338-P310-P321-P363-P405-P501	UN#:	1759
Hazard Statements:	H314	Packing Group:	Ⅲ
GHS Pictogram:

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P378
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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.
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P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
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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:
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P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
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P401
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P411 + P235	Keep cool.
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Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

[ CAS No. 37859-25-9 ]

Quality Control of [ 37859-25-9 ]

Related Doc. of [ 37859-25-9 ]

Product Details of [ 37859-25-9 ]

Calculated chemistry of [ 37859-25-9 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 37859-25-9 ]

Application In Synthesis of [ 37859-25-9 ]

[ 37859-25-9 ] Synthesis Path-Downstream 1~69

Related Functional Groups of [ 37859-25-9 ]

Aryls

Chlorides

Acyl Chlorides

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 37859-25-9 ]