Name: 2577-46-0|(2S,3S)-Methyl 2-amino-3-methylpentanoate|98%
Brand: Ambeed
SKU: A207987
Rating: 96 (35 reviews)

1
[ 67-56-1 ]
[ 73-32-5 ]
[ 2577-46-0 ]

Yield	Reaction Conditions	Operation in experiment
100%	Stage #1: methanol With thionyl chloride at -15 - 0℃; for 1h; Stage #2: L-isoleucine for 3h; Reflux;
96%	With hydrogenchloride
95%	With thionyl chloride at 0℃; for 12h; Reflux;	2 Synthesis of methyl L-isoleucinate (2): L-isoleucine 1 (20.0 g, 152.6 mmol) was taken in MeOH (200 mL) in a 500 rriL round bottom flask and cooled it down to 0°C. To it was added SOCl2 (56 mL, 763.3 mmol) and the reaction mixture was refluxed for 12h. It was then evaporated to dryness and triturated with pentane (50 mL) and ether (50 mL) separately. This was finally dried under high vaccum which affored a white solid 2 (21.1 g, 95%). This was then used in the next step without any further purification. 1H NMR (400 MHz, DMSO-de): δ 8.69 (s, 2H), 3.89 (d, J = 12.0 Hz, 1H), 3.73 (s, 3H), 1.95 (m, 1H), 1.40- 1.51 (m, 1H), 1.21-1.32 (m, 1H), 0.98 (d, J = 6.8 Hz, 6H).

92%	With thionyl chloride at 0 - 20℃;
87%	With thionyl chloride at -15 - 20℃;
82.57%	With thionyl chloride at 8 - 10℃; Reflux;	4.4. Synthesis of amino acid methyl ester hydrochloride General procedure: About 0.01-0.03 mol of L-amino acid (glycine, leucine, alanine, methionine,phenylalanine, isoleucine) were added to the reaction bottle and 25mLwater-free methanol was added. Under the cooling of ice water bath, slowlyadd (0.03-0.06) mol of thionyl chloride at 8-10 °C, continue to react for1-2 h after the addition, and then slowly reflux for 4-5 h. TLC trackingdetection, the developing agent was V (dichloromethane): V (methanol) 6:1, and ninhydrin was developed. After the reaction was completed, thesolvent was distilled off with an excess of thionylchloride, and then recrystallizedfrom methylene chloride and petroleum ether to give a white solid.
59%	With acetyl chloride at 0 - 20℃; for 6h; Inert atmosphere;
53%	Stage #1: methanol With thionyl chloride at 0℃; Stage #2: L-isoleucine In methanol at 0 - 20℃;
	With thionyl chloride
	With thionyl chloride at 0℃;
	With thionyl chloride
	With thionyl chloride at 70℃; for 2h;	Preparation of the amino acid derivatives 11-18, A general procedure General procedure: l-amino acid (5.6 mmol) was added into 10 mL mixed solution of SOCl2/CH3OH (1:10) and refluxed at 70 °C for 2 h. The solution was concentrated in vacuo and added hydrazine (27.2 mL, 561 mmol) and CH3OH (50 mL), and then stirred at rt for 12 h. The solution was concentrated in vacuo, and finally purified by column chromatography (10:1 CH2Cl2/CH3OH), affording l-amino acid derivative as white solid.
	With hydrogenchloride
	With thionyl chloride for 6h;
	With hydrogenchloride at 100℃; for 0.5h;
	With thionyl chloride
	With hydrogenchloride at 100℃; for 2h;
	With thionyl chloride at 0 - 25℃; for 18.5h;	General procedure: To a dried methanol (50 mL) solution of 4 (3.3 g, 20 mmol), thionyl chloride (3.57 g, 30 mmol) was slowly added over 30 minat 0 °C, and then, the solution was maintained at room temperature for 18 h. The solvent was evaporated to obtain a solid in quantitative yield, which was dissolved in dichloromethane (120 mL), and triethylamine (12.1 g, 120 mL) and di-tert-butyldicarbonate (9.6 g, 40 mmol) were added to the dichloromethane solution. The reaction mixture was stirred at 25 °C for 24 h. Afterc ompletion of the reaction, the solution was washed with phosphoric acid (50 x 3 mL), saturated sodium bicarbonate (50 x 3 mL) and saturated sodium chloride (50 x 3 mL), dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to afford a solid to which lithium aluminum hydride (13 mmol) in the presence of dried tetrahydrofuran (25 mL) was added at 0 °C. The reaction mixture was maintained at room temperature for 4 h, and then water was added until the lithium aluminum hydride reacted completely. Next, the solution was filtered, and the residue was washed with tetrahydrofuran (20 x 2 mL).The combined organic solvent phase was evaporated under reduced pressure to yield the crude product, which was purified using column chromatography (petroleum ether/acetone) to afford 5a-5g.
	With thionyl chloride at 0 - 20℃; for 24h;
	With acetyl chloride	5.1 (1) 100ml flask in L-Isoleucine (1g), acetyl chloride (2ml), followed by stirring by the addition of Methyl alcohol (7ml). After the reaction was evaporated under reduced pressure to obtain a precursor 14-1.
	With chloro-trimethyl-silane	3.1.2. General Procedure for Esterication of Amino Acids Methyl esters of d-Ile and O-benzyl-Ser derivatives were prepared as described in Li and Sha [38]using 2 mmol of amino acid, 0.5 mL of trimethylsilyl chloride (TMSCl), and 10 mL of methanol. Thereaction mixture was evaporated to dryness and stored in a desiccator.

Reference： [1]Zhang, Shuaibing; Huang, Ying; He, Shijun; Chen, Heping; Wu, Bin; Li, Shanyong; Zhao, Zhenzhu; Li, Zhenghui; Wang, Xian; Zuo, Jianping; Feng, Tao; Liu, Jikai [Journal of Organic Chemistry, 2018, vol. 83, # 17, p. 10158 - 10165]
[2]Location in patent: scheme or table Zhang, Yingjie; Feng, Jinhong; Jia, Yuping; Wang, Xuejian; Zhang, Lei; Liu, Chunxi; Fang, Hao; Xu, Wenfang [Journal of Medicinal Chemistry, 2011, vol. 54, # 8, p. 2823 - 2838]
[3]Current Patent Assignee: RAO M, Surya - WO2017/68477, 2017, A1 Location in patent: Page/Page column 60-61
[4]Location in patent: experimental part Zhou, Yinjian; Zhao, Ming; Wu, Yingting; Li, Chunyu; Wu, Jianhui; Zheng, Meiqing; Peng, Li; Peng, Shiqi [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 6, p. 2165 - 2172]
[5]Uehara, Tomoya; Rokugawa, Takemi; Kinoshita, Mai; Nemoto, Souki; Fransisco Lazaro, Guerra Gomez; Hanaoka, Hirofumi; Arano, Yasushi [Bioconjugate Chemistry, 2014, vol. 25, # 11, p. 2038 - 2045]
[6]Shi, Mingxing; Wang, Libo; Zhang, Long; Wang, Kexin; Zhang, Hualin; Wang, Yajing; Li, Chang; Han, Weina [Nucleosides, nucleotides and nucleic acids, 2020, vol. 40, # 1, p. 96 - 116]
[7]Tsuji, Hiroaki; Yamamoto, Hisashi [Journal of the American Chemical Society, 2016, vol. 138, # 43, p. 14218 - 14221]
[8]Location in patent: experimental part Umezawa, Naoki; Matsumoto, Nobuyoshi; Iwama, Shinsuke; Kato, Nobuki; Higuchi, Tsunehiko [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 17, p. 6340 - 6350]
[9]Kirmse,W.; Rauleder,G. [Justus Liebigs Annalen der Chemie, 1976, p. 1333 - 1342] Webb,R.G. et al. [Journal of Organic Chemistry, 1969, vol. 34, # 3, p. 576 - 580] Boissonnas et al. [Helvetica Chimica Acta, 1955, vol. 38, p. 1491,1499] Schwarz; Bumpus [Journal of the American Chemical Society, 1959, vol. 81, p. 890,894]
[10]Fukumoto, Kenta; Ohno, Hiroyuki [Angewandte Chemie - International Edition, 2007, vol. 46, # 11, p. 1852 - 1855]
[11]Jida, Mouhamad; Guillot, Régis; Ollivier, Jean [Tetrahedron Letters, 2007, vol. 48, # 49, p. 8765 - 8767]
[12]Location in patent: experimental part Liang, Qing-Feng; Liu, Juan-Juan; Chen, Jian [Tetrahedron Letters, 2011, vol. 52, # 31, p. 3987 - 3991]
[13]Location in patent: scheme or table Zhang, Yingjie; Fang, Hao; Feng, Jinhong; Jia, Yuping; Wang, Xuejian; Xu, Wenfang [Journal of Medicinal Chemistry, 2011, vol. 54, # 15, p. 5532 - 5539]
[14]Location in patent: scheme or table Bera, Saurav; Panda, Gautam [ACS Combinatorial Science, 2012, vol. 14, # 1, p. 1 - 4]
[15]Location in patent: experimental part Kimura, Miki; Wakimoto, Toshiyuki; Egami, Yoko; Tan, Karen Co; Ise, Yuji; Abe, Ikuro [Journal of Natural Products, 2012, vol. 75, # 2, p. 290 - 294]
[16]Arthur, Isaac N.; Hennessy, James E.; Padmakshan, Dharshana; Stigers, Dannon J.; Lesturgez, Stéphanie; Fraser, Samuel A.; Liutkus, Mantas; Otting, Gottfried; Oakeshott, John G.; Easton, Christopher J. [Chemistry - A European Journal, 2013, vol. 19, # 21, p. 6824 - 6830]
[17]Takada, Kentaro; Ninomiya, Akihiro; Naruse, Masato; Sun, Yi; Miyazaki, Masayuki; Nogi, Yuichi; Okada, Shigeru; Matsunaga, Shigeki [Journal of Organic Chemistry, 2013, vol. 78, # 13, p. 6746 - 6750]
[18]Yang, Dezhi; Wang, Peng; Liu, Jianzhen; Xing, Hualu; Liu, Yang; Xie, Wencheng; Zhao, Guisen [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 1, p. 366 - 373]
[19]Singhamahapatra, Anadi; Sahoo, Laxminarayan; Varghese, Babu; Loganathan, Duraikkannu [RSC Advances, 2014, vol. 4, # 35, p. 18038 - 18043]
[20]Current Patent Assignee: SAMSUNG C&T CORPORATION - KR2015/127464, 2015, A Location in patent: Paragraph 0217; 0218
[21]Bárta, Pavel; Doležal, Martin; Horáček, Ondřej; Jand'Ourek, Ondřej; Janoušek, Jiří; Juhás, Martin; Konečná, Klára; Kučera, Radim; Kučerová, Lucie; Kubíček, Vladimír; Kuneš, Jiří; Paterová, Pavla; Zitko, Jan [Molecules, 2020, vol. 25, # 7]

2
[ 2577-46-0 ]
[ 1164-16-5 ]
[ 27482-73-1 ]

Yield	Reaction Conditions	Operation in experiment
87%	With 1-hydroxy-pyrrolidine-2,5-dione; dicyclohexyl-carbodiimide In various solvent(s) at 0℃;
	With dicyclohexyl-carbodiimide; acetonitrile

Reference： [1]Ivanov, A. K.; Karel'skii, V. N.; Krysin, E. P.; Lavut, E. E.; Zel'tser, I. E.; Antonov, A. A. [Chemistry of Natural Compounds, 1989, vol. 25, p. 103 - 108][Khimiya Prirodnykh Soedinenii, 1989, # 1, p. 116 - 122]
[2]Guttmann et al. [Naturwissenschaften, 1957, vol. 44, p. 632]

3
[ 67-56-1 ]
[ 319-78-8 ]
[ 2577-46-0 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; at 75℃; for 12h;Reflux;	General procedure: A mixture of amino acid (1 mmol) and thionyl chloride (1.5 mmol) in 30 mL methanol and the contents were refluxed at 75 C for 12 h. The reaction mixture was cooled to RT and methanol was distilled and product was dried under vacuum.

Reference： [1]Collection of Czechoslovak Chemical Communications,1963,vol. 28,p. 1691 - 1705
[2]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 209 - 212
[3]Journal of Organic Chemistry,2016,vol. 81,p. 5681 - 5689

4
[ 2577-46-0 ]
[ 24629-25-2 ]

Reference： [1]Bulletin des Societes Chimiques Belges,1991,vol. 100,p. 63 - 77
[2]Chemical and pharmaceutical bulletin,1969,vol. 17,p. 2075 - 2082

5
[ 4530-20-5 ]
[ 2577-46-0 ]
[ 59408-93-4 ]

Yield	Reaction Conditions	Operation in experiment
	With dicyclohexyl-carbodiimide In dichloromethane
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0 - 20℃;	53A Methyl N-(tert-butoxycarbonyl)glycyl-L-isoleucinate Methyl L-isoleucinate (3.00 g, 20.7 mmol) and N-(tert-butoxycarbonyl)glycine (3.98 g, 22.7 mmol) were dissolved in DMF (20 mL). This solution was cooled to 0-5°C in an ice bath. N,N-diisopropylethylamine (3.6 mL, 21 mmol), 1H-benzotriazol-1-ol hydrate (316 mg, 2.07 mmol) and 1-(3-dimethylaminopropyl)- 3-ethylcarbodiimidhydrochloride (4.36 g, 22.7 mmol) were added and the mixture was stirred at room temperature. The reaction mixture was quenched with concentrated aqueous ammonium chloride and ex- tracted with three portions of ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate and concentrated. The crude product was purified by chromatography on silica gel (cyclohexane / ethyl acetate 0 % to 10 %) to give the title compound, 5.40 g (90 % purity, 78 % yield). LC-MS (Method 11): Rt = 1.13 min; MS (ESI pos): m/z = 247 [M-tBu]+ H-NMR (400 MHz, DMSO-d6) d [ppm]: 0.819 (4.90), 0.835 (8.09), 0.853 (2.63), 1.152 (0.40), 1.174 (0.45), 1.354 (1.52), 1.375 (16.00), 1.459 (0.46), 3.561 (0.84), 3.571 (0.98), 3.577 (1.45), 3.594 (0.81), 3.630 (11.35), 4.220 (0.63), 4.237 (0.78), 4.240 (0.82), 4.257

Reference： [1]Smith, Grant Gill; Evans, Robert C.; Baum, Rocky [Journal of the American Chemical Society, 1986, vol. 108, # 23, p. 7327 - 7332]
[2]Current Patent Assignee: BAYER AG - WO2020/225095, 2020, A1 Location in patent: Page/Page column 169-170

6
[ 13734-41-3 ]
[ 2577-46-0 ]
[ 33857-87-3 ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: t-Boc-L-valine With ethyl 2-cyano-2-(2-nitrobenzenesulfonyloxyimino)acetate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.0833333h; Stage #2: L-isoleucine methyl ester In dichloromethane at 20℃; for 4h;
82%	With benzotriazol-1-ol; dicyclohexyl-carbodiimide
79.84%	With benzotriazol-1-ol; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 20℃; for 48h;

With 4-methyl-morpholine; isobutyl chloroformate In tetrahydrofuran

Reference： [1]Giri, Rajat Subhra; Pal, Saikat; Roy, Sayanta; Dolai, Gobinda; Manne, Srinivasa Rao; Paul, Sandip; Mandal, Bhubaneswar [Peptide Science, 2021, vol. 113, # 2]
[2]Suzuki; Sasaki; Endo; Mihara [Chemical and Pharmaceutical Bulletin, 1981, vol. 29, # 1, p. 233 - 237]
[3]Ray, Sudipta; Das, Apurba K.; Drew, Michael G. B.; Banerjee, Arindam [Chemical Communications, 2006, # 40, p. 4230 - 4232]
[4]Location in patent: scheme or table Zhang, Yingjie; Feng, Jinhong; Jia, Yuping; Wang, Xuejian; Zhang, Lei; Liu, Chunxi; Fang, Hao; Xu, Wenfang [Journal of Medicinal Chemistry, 2011, vol. 54, # 8, p. 2823 - 2838]

7
[ 13139-16-7 ]
[ 2577-46-0 ]
N-alpha-t-butyloxycarbonyl-L-isoleucyl-L-isoleucine methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With benzotriazol-1-ol; dicyclohexyl-carbodiimide
81%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 16h;
72%	Stage #1: N-(tert-butyloxycarbonyl)-L-isoleucine; L-isoleucine methyl ester With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate In dichloromethane; N,N-dimethyl-formamide for 0.166667h; Stage #2: With triethylamine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 14h;	2 Synthesis of methyl (tert-butoxycarbonyl)-L-isoleucyl-L-isoleucinate (4): To a stirred solution of (teri-butoxycarbonyl)-L-isoleucine 3 (13 g, 0.056 mol) and methyl L- lsoleucinate 2 (10.21 g, 0.056 mol) in DCM:DMF (200 mL, 1 : 1), HBTU (23.36 g, 0.061 mol) was added and the reaction mixture was stirred for 10 min. To this reaction mixture Et3N (19.4 mL, 0.14 mol) was added very slowly in order to control the exothermic reaction. The mixture was then stirred at rt and monitored by TLC analysis. After 14h, water (200 mL) was added to it and extracted with ethyl acetate (2 x 200 mL). The combined organic layer was washed with ice cold water (3 x 50 mL) and saturated NaHCC solution (3 x 50 mL). It was dried over anhydrous Na2S04 and concentrated under reduced pressure. The resulting crude residue was purified by flash chromatography on silica gel (100-200 mesh) using 20% EtOAc-hexane as an eluent to obtain 4 (14.6 g, 72%) as a white solid. . 1H NMR (400 MHz, CDC13): δ 6.33 (m, 1H), 5.01 (m, 1H), 4.58 (m, 1H), 3.93 (m, 1H), 3.73 (s, 3H), 1.89 (m, 2H), 1.79 (m, 2H), 1.44 (s, 9H), 0.94 (m, 12H). ELSD: 303.2 [M+H-56]; 99.85% (purity).

	With dicyclohexyl-carbodiimide In pyridine; dichloromethane at 0 - 20℃;
	With 4-methyl-morpholine; benzotriazol-1-ol; dicyclohexyl-carbodiimide In ethyl acetate at 20℃; for 2h; Inert atmosphere;
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at -10℃; for 2h;

Reference： [1]Suzuki; Sasaki; Endo; Mihara [Chemical and Pharmaceutical Bulletin, 1981, vol. 29, # 1, p. 233 - 237]
[2]Location in patent: experimental part Umezawa, Naoki; Matsumoto, Nobuyoshi; Iwama, Shinsuke; Kato, Nobuki; Higuchi, Tsunehiko [Bioorganic and Medicinal Chemistry, 2010, vol. 18, # 17, p. 6340 - 6350]
[3]Current Patent Assignee: RAO M, Surya - WO2017/68477, 2017, A1 Location in patent: Page/Page column 61
[4]Lin; Chen; You; Chen Liu; Lee [Journal of Natural Products, 2000, vol. 63, # 10, p. 1338 - 1343]
[5]Location in patent: experimental part Eum, Heesung; Lee, Yuno; Kim, Songmi; Baek, Ayoung; Son, Minky; Lee, Keun Woo; Ko, Seung Whan; Kim, Sunghoon; Yun, Sae Young; Lee, Won Koo; Ha, Hyun-Joon [Bulletin of the Korean Chemical Society, 2010, vol. 31, # 3, p. 611 - 614]
[6]Zhan, Bei-Bei; Li, Ya; Xu, Jing-Wen; Nie, Xing-Liang; Fan, Jun; Jin, Liang; Shi, Bing-Feng [Angewandte Chemie - International Edition, 2018, vol. 57, # 20, p. 5858 - 5862][Angew. Chem., 2018, vol. 130, # 20, p. 5960 - 5964,5]

8
[ 13726-67-5 ]
[ 2577-46-0 ]
(2S,3R)-2-((S)-2-tert-Butoxycarbonylamino-3-carboxy-propionylamino)-3-methyl-pentanoic acid methyl ester [ No CAS ]

Reference： [1]Journal of general chemistry of the USSR,1986,vol. 56,p. 1446 - 1449
Zhurnal Obshchei Khimii,1986,vol. 56,p. 1631 - 1635

9
N-(9-fluorenylmethoxycarbonyl)isoleucine methyl ester [ No CAS ]
[ 2577-46-0 ]

Yield	Reaction Conditions	Operation in experiment
98%	With potassium fluoride; 18-crown-6 ether In N,N-dimethyl-formamide for 8h; Ambient temperature;
87%	With sodium azide In N,N-dimethyl-formamide at 50℃; for 3h;
79%	With triethylamine; 1-butyl-3-methylimidazolium Tetrafluoroborate In neat (no solvent) at 25℃; Green chemistry;

Reference： [1]Jiang; Li; Joullie [Synthetic Communications, 1994, vol. 24, # 2, p. 187 - 195]
[2]Chen, Chun-Chi; Rajagopal, Basker; Liu, Xuan Yu; Chen, Kuan Lin; Tyan, Yu-Chang; Lin, Fui; Lin, Po-Chiao [Amino Acids, 2014, vol. 46, # 2, p. 367 - 374]
[3]Di Gioia; Costanzo; De Nino; Maiuolo; Nardi; Olivito; Procopio [RSC Advances, 2017, vol. 7, # 58, p. 36482 - 36491]

10
[ 2577-46-0 ]
[ 45233-75-8 ]
[ 168420-31-3 ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 4014 - 4018

11
[ 2577-46-0 ]
[ 24424-99-5 ]
(2s,3s)-2-isocyanato-3-methylvaleric acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With dmap In dichloromethane at 25℃; for 0.166667h;

Reference： [1]Knölker, Hans-Joachim; Braxmeier, Tobias [Synlett, 1997, vol. 1997, # 8, p. 925 - 928]

12
[ 13139-15-6 ]
[ 2577-46-0 ]
[ 53613-22-2 ]

Yield	Reaction Conditions	Operation in experiment
81%	With dicyclohexyl-carbodiimide In tetrahydrofuran at 0 - 20℃; for 20h;	tert-Butoxycarbonyl-L-leucyl-L-isoleucine methyl ester (1) General procedure: To a solution of 23.13 g (100 mmol) tert-butoxycarbonyl-L-leucine in 150 mL of THF cooled to 0 °C at vigorous stirring were added in succession solutions of 21.63 g (105 mmol) of dicyclohexylcarbodiimide in 150 mL of THF and 15.97 g (110 mmol) of L-isoleucine methyl ester in 100 mL of THF. The reaction mixture was warmed to room temperature, and the stirring was continued for 20 h. The separated precipitate was filtered off, the solvent was removed at a reduced pressure, the reaction product was extracted from the residue with ethyl ether, the solution obtained was filtered, the solvent was removed at a reduced pressure, residue was washed with cold hexane and dried in a vacuum. Yield 29.04 g (81%), mp 118-120 °, [α]D20 -32° (c 3, MeOH). IR spectrum, ν, cm-1: 1752, 1688, 1655(C=O), 1555, 1527 (N-Hamide). 1H NMR spectrum (CDCl3), δ, ppm: 0.77-0.86 m (12H, 4CH3), 1.05-1.12 m (1H, CH), 1.34 s (9H, 3CH3), 1.55-1.62 m (4H, 2CH2), 1.77-1.82 m (1H, CH), 3.63 s (3H, CH3), 4.05-4.11 m (1H, CH), 4.42-4.46 m (1H, CH). 13C NMR spectrum (CDCl3), δ, ppm: 11.29, 15.19, 21.93, 22.63, 24.47, 24.79, 28.09, 37.56, 40.61, 51.77, 52.83, 56.23, 79.63, 155.59, 171.95, 172.34. Found, %: C 60.53; H 9.81; N 7.62. C18H34N2O5. Calculated, %: C 60.31; H 9.56; N 7.81.
	With dicyclohexyl-carbodiimide In pyridine; dichloromethane at 0 - 20℃;
	With 4-methyl-morpholine; benzotriazol-1-ol; dicyclohexyl-carbodiimide In ethyl acetate at 20℃; for 2h; Inert atmosphere;

With benzotriazol-1-ol; dicyclohexyl-carbodiimide In dichloromethane; N,N-dimethyl-formamide at 20℃; Cooling with ice;

Reference： [1]Gaidukevich; Popova; Zubreichuk; Knizhnikov [Russian Journal of Organic Chemistry, 2015, vol. 51, # 5, p. 615 - 618][Zh. Org. Khim., 2015, vol. 51, # 5, p. 637 - 640,4]
[2]Lin; Chen; You; Chen Liu; Lee [Journal of Natural Products, 2000, vol. 63, # 10, p. 1338 - 1343]
[3]Location in patent: experimental part Eum, Heesung; Lee, Yuno; Kim, Songmi; Baek, Ayoung; Son, Minky; Lee, Keun Woo; Ko, Seung Whan; Kim, Sunghoon; Yun, Sae Young; Lee, Won Koo; Ha, Hyun-Joon [Bulletin of the Korean Chemical Society, 2010, vol. 31, # 3, p. 611 - 614]
[4]Location in patent: experimental part Koley, Pradyot; Drew, Michael G.B.; Pramanik, Animesh [Journal of Nanoscience and Nanotechnology, 2011, vol. 11, # 8, p. 6747 - 6756]

13
[ 2577-46-0 ]
[ 37517-81-0 ]
[ 308277-47-6 ]

Yield	Reaction Conditions	Operation in experiment
88%	With 4-methyl-morpholine In dichloromethane at -15 - 20℃; for 12h;

Reference： [1]Falorni, Massimo; Giacomelli, Giampaolo; Porcheddu, Andrea; Dettori, Giovanna [European Journal of Organic Chemistry, 2000, # 18, p. 3217 - 3222]

14
[ 2577-46-0 ]
[ 13734-34-4 ]
[ 297740-86-4 ]

Yield	Reaction Conditions	Operation in experiment
84%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 1.08h;	General procedure for coupling reaction: General procedure: the methyl ester of the C-terminal amino acid (1 eq) and the Boc-protected N-terminal amino acid (1.1 eq) were dissolved in dry solvent CH2Cl2 (15 mL), followed by addition of DMAP (1 eq). The reaction mixture was stirred for 5 min at rt whereupon EDC (1.3 eq) was added. The reaction was there after stirred for 1 h at rt. The reaction mixture was then washed with H2O. The aqueous layer was extracted with AcOEt. The organic layer was dried on MgSO4, concentrated in vacuo and the crude product was purified by flash chromatography.
78%	With dicyclohexyl-carbodiimide In pyridine; dichloromethane at 0 - 20℃; for 4.5h;

Reference： [1]Laville, Rmi; Nguyen, Thanh Binh; Moriou, Cline; Petek, Sylvain; Debitus, Ccile; Al-Mourabit, Ali [Heterocycles, 2015, vol. 90, # 2, p. 1351 - 1366]
[2]Lin; Chen; You; Chen Liu; Lee [Journal of Natural Products, 2000, vol. 63, # 10, p. 1338 - 1343]

15
[ 2577-46-0 ]
[ 18942-49-9 ]
BocHN-D-Phe-Ile-OMe [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate In dichloromethane for 0.0833333h;
	With dicyclohexyl-carbodiimide In pyridine; dichloromethane at 0 - 20℃;

Reference： [1]Zhang, Yuqi; Islam, Md. Amirul; McAlpine, Shelli R. [Organic Letters, 2015, vol. 17, # 21, p. 5149 - 5151]
[2]Lin; Chen; You; Chen Liu; Lee [Journal of Natural Products, 2000, vol. 63, # 10, p. 1338 - 1343]

16
[ 2577-46-0 ]
[ 20691-84-3 ]
[ 395647-13-9 ]

Yield	Reaction Conditions	Operation in experiment
79%	With benzotriazol-1-ol; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide

Reference： [1]Sameiro, M; Gonçalves, T; Maia, Hernâni L.S [Tetrahedron Letters, 2001, vol. 42, # 44, p. 7775 - 7777]

17
[ 2577-46-0 ]
[ 13139-14-5 ]
[ 72156-60-6 ]

Yield	Reaction Conditions	Operation in experiment
92%	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;
	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine; HATU In dichloromethane at 20℃; Inert atmosphere;

Reference： [1]Xue, Fengtian; Seto, Christopher T. [Journal of Medicinal Chemistry, 2005, vol. 48, # 22, p. 6908 - 6917]
[2]Singh, Erinprit K.; Nazarova, Lidia A.; Lapera, Stephanie A.; Alexander, Leslie D.; McAlpine, Shelli R. [Tetrahedron Letters, 2010, vol. 51, # 33, p. 4357 - 4360]

18
[ 866555-29-5 ]
[ 2577-46-0 ]
[ 866555-30-8 ]

Yield	Reaction Conditions	Operation in experiment
91%	With 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 25℃; for 17h;
91%	With 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 24h;
91%	With 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 25℃; for 24h;

Reference： [1]Nicolaou; Kim, David W.; Schlawe, Daniel; Lizos, Dimitrios E.; De Noronha, Rita G.; Longbottom, Deborah A. [Angewandte Chemie - International Edition, 2005, vol. 44, # 31, p. 4925 - 4929]
[2]Nicolaou; Lizos, Dimitrios E.; Kim, David W.; Schlawe, Daniel; De Noronha, Rita G.; Longbottom, Deborah A.; Rodriquez, Manuela; Bucci, Mariarosaria; Cirino, Giuseppe [Journal of the American Chemical Society, 2006, vol. 128, # 13, p. 4460 - 4470]
[3]Nicolaou; Schlawe, Daniel; Kim, David W.; Longbottom, Deborah A.; De Noronha, Rita G.; Lizos, Dimitrios E.; Manam, Rama Rao; Faulkner, D. John [Chemistry - A European Journal, 2005, vol. 11, # 21, p. 6197 - 6211]

19
[ 2577-46-0 ]
[ 29776-78-1 ]
[ 276257-21-7 ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: (S)-1-(2-tert-butoxycarbonylaminoacetyl)pyrrolidine-2-carboxylic acid benzyl ester With hydrogen In methanol Stage #2: L-isoleucine methyl ester With benzotriazol-1-ol; dicyclohexyl-carbodiimide; trifluoroacetic acid Further stages.;

Reference： [1]Li, Quan; Moutiez, Mireille; Charbonnier, Jean-Baptiste; Vaudry, Karine; Ménez, André; Quéméneur, Eric; Dugave, Christophe [Journal of Medicinal Chemistry, 2000, vol. 43, # 9, p. 1770 - 1779]

20
[ 2577-46-0 ]
[ 3303-84-2 ]
[ 936124-39-9 ]

Yield	Reaction Conditions	Operation in experiment
90%	With benzotriazol-1-ol; dicyclohexyl-carbodiimide In ethyl acetate; N,N-dimethyl-formamide at 20℃; for 72h;

Reference： [1]Guha, Samit; Drew, Michael G. B.; Banerjee, Arindam [Organic Letters, 2007, vol. 9, # 7, p. 1347 - 1350]

21
[ 2577-46-0 ]
[ 66863-43-2 ]
[ 1034296-19-9 ]

Yield	Reaction Conditions	Operation in experiment
92%	With benzotriazol-1-ol; dicyclohexyl-carbodiimide In tetrahydrofuran at 0 - 20℃; for 18h;
90%	Stage #1: (3S)-2-tert-butoxycarbonyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid With benzotriazol-1-ol In tetrahydrofuran at 0℃; for 0.166667h; Stage #2: L-isoleucine methyl ester With 4-methyl-morpholine; dicyclohexyl-carbodiimide In tetrahydrofuran at 0 - 20℃; for 18h;

Reference： [1]Wu, Guofeng; Liu, Jiawang; Bi, Lanrong; Zhao, Ming; Wang, Chao; Baudy-Floc'h, Michèle; Ju, Jingfang; Peng, Shiqi [Tetrahedron, 2007, vol. 63, # 25, p. 5510 - 5528]
[2]Location in patent: experimental part Liu, Jiawang; Zhao, Ming; Cui, Guohui; Zhang, Xiaoyi; Wang, Jun; Peng, Shiqi [Journal of Medicinal Chemistry, 2008, vol. 51, # 15, p. 4715 - 4723]

22
[ 2577-46-0 ]
[ 36077-41-5 ]

Reference： [1]Journal of Biological Chemistry,1952,vol. 199,p. 801,808
[2]Bulletin of the Chemical Society of Japan,1973,vol. 46,p. 2190 - 2193
[3]Russian Journal of Organic Chemistry,2015,vol. 51,p. 615 - 618
Zh. Org. Khim.,2015,vol. 51,p. 637 - 640,4

23
[ 2577-46-0 ]
[ 453-71-4 ]
[ 907582-63-2 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In methanol at 65℃; for 48h;	2.1 EXAMPLE 2Synthesis of Compound 3Step i[0155] To a solution of isoleucine methyl ester (4.0 g, 22.02 mmol) andDIEA (2.82 g, 22.02 mmol) in methanol (20 mL) 4-fluoro-2-nitrobenzoic acid(1.02 g, 5.50 mmol) was added. The mixture was stirred at 65 0C for 48 h and then evaporated to dryness, dissolved in ethyl acetate and washed with water three times and then with a saturated NaCI solution. The organic layer was dried over Mg2SO4 and the course of the reaction verified by LC-MS.
	In methanol for 72h; Reflux;

Reference： [1]Current Patent Assignee: ACADIA PHARMACEUTICALS INC - WO2006/89286, 2006, A2 Location in patent: Page/Page column 42
[2]Location in patent: scheme or table Malik, Leila; Kelly, Nicholas M.; Ma, Jian-Nong; Currier, Erika A.; Burstein, Ethan S.; Olsson, Roger [Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 6, p. 1729 - 1732]

24
[ 50-00-0 ]
[ 931-53-3 ]
[ 2577-46-0 ]
[ 35737-15-6 ]
C₂₅H₃₄N₄O₃ [ No CAS ]

Reference： [1]Synthesis,2008,p. 2077 - 2082

25
[ 2577-46-0 ]
[ 24601-74-9 ]
C₁₃H₂₄N₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	Stage #1: (S)-4-isopropyloxazolidine-2,5-dione With chloro-trimethyl-silane; triethylamine In tetrahydrofuran at -30℃; for 4.5h; Stage #2: methyl L-isoleucinate With triethylamine In tetrahydrofuran at 0℃; for 2h; regioselective reaction;

Reference： [1]Location in patent: experimental part Mateos-Caro, Julia; Robin, Yves; Levacher, Vincent; Marsais, Francis [Synlett, 2009, # 2, p. 279 - 283]

26
[ 2577-46-0 ]
[ 108-24-7 ]
[ 2256-76-0 ]

Yield	Reaction Conditions	Operation in experiment
100%	In dichloromethane at 20℃; for 4h;
100%	With sodium hydrogencarbonate In dichloromethane; water at 25℃; for 4h;

Reference： [1]Location in patent: experimental part De Marco, Rosaria; Gioia, Maria Luisa Di; Leggio, Antonella; Liguori, Angelo; Viscomi, Maria Caterina [European Journal of Organic Chemistry, 2009, # 22, p. 3795 - 3800]
[2]Di Gioia; Costanzo; De Nino; Maiuolo; Nardi; Olivito; Procopio [RSC Advances, 2017, vol. 7, # 58, p. 36482 - 36491]

27
[ 2577-46-0 ]
[ 1483-73-4 ]
[ 1224466-99-2 ]

Reference： [1]Synthetic Communications,2010,vol. 40,p. 1161 - 1179

28
[ 2577-46-0 ]
[ 1161-13-3 ]
[ 1229693-85-9 ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: N-Cbz-L-Phe With sodium azide; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In tetrahydrofuran; dimethyl sulfoxide at 0℃; for 0.333333h; Stage #2: In tetrahydrofuran; toluene at 45℃; Sonication; Stage #3: L-isoleucine methyl ester In tetrahydrofuran; dichloromethane; toluene for 1h; Sonication;

Reference： [1]Location in patent: experimental part Basavaprabhu; Narendra; Lamani, Ravi S.; Sureshbabu, Vommina V. [Tetrahedron Letters, 2010, vol. 51, # 22, p. 3002 - 3005]

29
[ 2577-46-0 ]
(3S)-2-tert-butoxycarbonyl-1,2,3,4-tetrahydroisoquinole-3-carboxylic acid [ No CAS ]
[ 1034535-22-2 ]

Yield	Reaction Conditions	Operation in experiment
89%	Stage #1: (3S)-2-tert-butoxycarbonyl-1,2,3,4-tetrahydroisoquinole-3-carboxylic acid With benzotriazol-1-ol; dicyclohexyl-carbodiimide In tetrahydrofuran at 0℃; Stage #2: L-isoleucine methyl ester With 4-methyl-morpholine In tetrahydrofuran at 20℃; for 12h;	4.1.4. General procedure for preparing (S)-2-Boc-1,2,3,4-tetrahydroisoquinoline-3-carbonylamino acid methyl esters (3a-q) General procedure: At 0 °C and with stirring, to the solution of 0.256 g (0.924 mmol) of (S)-2-Boc-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, 2 mL of anhydrous THF 0.151 g (0.109 mmol) of HOBt was added, and stirred for 10 min. Then, 0.228 g (0.108 mmol) of DCC was added to form reaction mixture A. To the suspension of 0.102 mmol of HCl·AA-OMe in 4 ml of anhydrous THF, 1 mL of N-methylmorpholine was added and stirred at room temperature for 35 min to form reaction mixture B (pH 9). The reaction mixture A and B were combined, stirred at room temperature for 12 h, and TLC (ethyl acetate/petroleum ether, 1:3) indicated the complete disappearance of 3S-2-Boc-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid. The formed precipitate of DCU was removed by filtration, and the filtrate was evaporated under vacuum. The residue was dissolved in 50 ml of ethyl acetate, the formed solution was washed successively with saturated aqueous solution of NaHCO3 (30 mL × 3), 5% aqueous solution of KHSO4 (30 mL × 3) and saturated aqueous solution of NaCl (30 mL × 3), and dried with anhydrous Na2SO4.

Reference： [1]Location in patent: experimental part Wang, Hong; Peng, Le; Zhao, Ming; Liu, Jiawang; Zhang, Xiaoyi; Wang, Yuji; Wu, Jianhui; Li, Li; Peng, Shiqi [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 2, p. 871 - 882]

30
[ 2577-46-0 ]
C₁₆H₂₀N₂O₅ [ No CAS ]
[ 1244610-31-8 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In dichloromethane at 20℃; for 0.5h;	5.1.1.7. 6-Benzyloxycarbonylamino-2-(3-methoxycarbonylmethyl-ureido)-hexanoic acid methyl ester (3a) General procedure: To a mixture of N6-cbz-l-lyscine methyl ester hydrochloride (6.94 g, 21 mmol) in saturated NaHCO3 (80 mL) and DCM (80 mL) was added triphosgene (2.08 g, 7 mmol), and the reaction mixture was vigorously stirred under ice-water bath for 15 min and the organic layer was collected. The water layer was extracted with DCM for three times and the organic phase was combined and dried with MgSO4. After the solvent removed under vaccum, the residue was dissolved in DCM (20 mL). This solution was then added to the mixture of l-glycine methyl ester hydrochloride (2.64 g, 21 mmol) and triethylamine (2.12 g, 21 mmol). The reaction mixture was stirred at room temperature for 30 min and then the solvent was removed under low pressure. The residue was taken up with ethyl acetate (40 mL) and washed with 1 N HCl (10 mL) and brine (20 mL). The organic phase was dried with MgSO4 and compound 3a was obtained as yellow oil and separated by silica gel column chromatography (petroleum ether/ethyl acetate = 1:1)

Reference： [1]Location in patent: experimental part Su, Li; Fang, Hao; Yang, Kanghui; Xu, Yingying; Xu, Wenfang [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 2, p. 900 - 906]

31
[ 2577-46-0 ]
[ 69872-65-7 ]
[ 1269631-91-5 ]

Yield	Reaction Conditions	Operation in experiment
83%	With benzotriazol-1-ol; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 20℃; Cooling with ice;

Reference： [1]Jana, Poulami; Maity, Sibaprasad; Maity, Suman Kumar; Haldar, Debasish [Chemical Communications, 2011, vol. 47, # 7, p. 2092 - 2094]

32
[ 2577-46-0 ]
[ 24424-99-5 ]
[ 17901-01-8 ]

Yield	Reaction Conditions	Operation in experiment
97%	In water at 110℃; for 0.0833333h; Microwave irradiation; Green chemistry; chemoselective reaction;
	With triethylamine In dichloromethane at 25℃; for 12h; Inert atmosphere;
	With triethylamine In dichloromethane at 25℃; for 24h;	General procedure: To a dried methanol (50 mL) solution of 4 (3.3 g, 20 mmol), thionyl chloride (3.57 g, 30 mmol) was slowly added over 30 minat 0 °C, and then, the solution was maintained at room temperature for 18 h. The solvent was evaporated to obtain a solid in quantitative yield, which was dissolved in dichloromethane (120 mL), and triethylamine (12.1 g, 120 mL) and di-tert-butyldicarbonate (9.6 g, 40 mmol) were added to the dichloromethane solution. The reaction mixture was stirred at 25 °C for 24 h. Afterc ompletion of the reaction, the solution was washed with phosphoric acid (50 x 3 mL), saturated sodium bicarbonate (50 x 3 mL) and saturated sodium chloride (50 x 3 mL), dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to afford a solid to which lithium aluminum hydride (13 mmol) in the presence of dried tetrahydrofuran (25 mL) was added at 0 °C. The reaction mixture was maintained at room temperature for 4 h, and then water was added until the lithium aluminum hydride reacted completely. Next, the solution was filtered, and the residue was washed with tetrahydrofuran (20 x 2 mL).The combined organic solvent phase was evaporated under reduced pressure to yield the crude product, which was purified using column chromatography (petroleum ether/acetone) to afford 5a-5g.

Reference： [1]Nardi; Cano, N. Herrera; Costanzo; Oliverio; Sindona; Procopio [RSC Advances, 2015, vol. 5, # 24, p. 18751 - 18760]
[2]Ko, Eunhwa; Liu, Jing; Perez, Lisa M.; Lu, Genliang; Schaefer, Amber; Burgess, Kevin [Journal of the American Chemical Society, 2011, vol. 133, # 3, p. 462 - 477]
[3]Yang, Dezhi; Wang, Peng; Liu, Jianzhen; Xing, Hualu; Liu, Yang; Xie, Wencheng; Zhao, Guisen [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 1, p. 366 - 373]

33
[ 2577-46-0 ]
[ 163979-02-0 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrazine hydrate In methanol at 20℃; for 12h;	Preparation of the amino acid derivatives 11-18, A general procedure General procedure: l-amino acid (5.6 mmol) was added into 10 mL mixed solution of SOCl2/CH3OH (1:10) and refluxed at 70 °C for 2 h. The solution was concentrated in vacuo and added hydrazine (27.2 mL, 561 mmol) and CH3OH (50 mL), and then stirred at rt for 12 h. The solution was concentrated in vacuo, and finally purified by column chromatography (10:1 CH2Cl2/CH3OH), affording l-amino acid derivative as white solid.
	With hydrazine hydrate

Reference： [1]Location in patent: experimental part Liang, Qing-Feng; Liu, Juan-Juan; Chen, Jian [Tetrahedron Letters, 2011, vol. 52, # 31, p. 3987 - 3991]
[2]Arthur, Isaac N.; Hennessy, James E.; Padmakshan, Dharshana; Stigers, Dannon J.; Lesturgez, Stéphanie; Fraser, Samuel A.; Liutkus, Mantas; Otting, Gottfried; Oakeshott, John G.; Easton, Christopher J. [Chemistry - A European Journal, 2013, vol. 19, # 21, p. 6824 - 6830]

34
[ 2577-46-0 ]
9-[((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-Hydroxy-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-icosahydro-cyclopenta[a]chrysene-3a-carbonyl)-amino]-nonanoic acid [ No CAS ]
[ 1394157-76-6 ]

Yield	Reaction Conditions	Operation in experiment
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃;	Method for synthesis of compound 13 and can be used for obtaining 11, 12, 14 - 39: In a solution of 13b (150 mg, 0.25 mmol) in DCM (8 ml), was added EDC-HCl (0.75 mmol), TEA (1.9 mmol), and methyl glutaminate (1.6 mmol). After stirring overnight at rt, the reaction mixture was diluted with DCM (40 ml), washed with water and brine. The organic layer was dried with Na2SO4 and concentrated in vacuum. The residue was chromatographed on Si-gel and reverse phase HPLC to yield compound 13 (120 mg, 64% yield).
	With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;

Reference： [1]Dang, Zhao; Qian, Keduo; Ho, Phong; Zhu, Lei; Lee, Kuo-Hsiung; Huang, Li; Chen, Chin-Ho [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 16, p. 5190 - 5194]
[2]Dang, Zhao; Ho, Phong; Zhu, Lei; Qian, Keduo; Lee, Kuo-Hsiung; Huang, Li; Chen, Chin-Ho [Journal of Medicinal Chemistry, 2013, vol. 56, # 5, p. 2029 - 2037]

35
[ 2577-46-0 ]
[ 127132-38-1 ]
(2S,3S)-methyl 2-((S)-3-(4-(allyloxy)phenyl)-2-(tertbutoxycarbonylamino)propanamido)-3-methylpentanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With 1-hydroxy-7-aza-benzotriazole; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 18h; Inert atmosphere;

Reference： [1]Jones, Seth A.; Neilsen, Paul M.; Siew, Limei; Callen, David F.; Goldfarb, Nathan E.; Dunn, Ben M.; Abell, Andrew D. [ChemMedChem, 2013, vol. 8, # 12, p. 1918 - 1921]

36
[ 2577-46-0 ]
[ 141321-52-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 366 - 373

37
[ 2577-46-0 ]
C₁₆H₂₂N₂O₅ [ No CAS ]
C₂₃H₃₅N₃O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
36%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0 - 20℃;	Syntheses of dipeptide (7) General procedure: A solution of N-(2-amioethyl)troponyl)glycine (6) (200 mg, 0.62 mmol) in anhydrous dichloromethane (10 mL) was cooled to 0 oC, and then EDC-HCl (142 mg, 0.744 mmol) was added, stirred for 5 min at 0oC. Then L-Phenylalanine methyl ester hydrochloride (160 mg, 0.744 mmol) and Triethylamine (0.26 mL, 1.86 mmol) was added together. This reaction mixture was continued to stirrer at room temperature (rt) for overnight. After completion of reaction, the reaction mixture was concentrated to dryness under reduced pressure. Concentrated reaction residue was re-dissolved in DCM (30 mL) and then washed with water thrice (3*30mL) followed by saturated sodium bicarbonate (20 mL) by following extraction method. The washed organic layers were combined together and concentrated under reduced pressure and then loaded on silicagel column for purification by EtOAc/Hexane to obtain desired product (7). The major component was isolated with EtOAc/Hexane (30:70) and characterized as desired product (120 mg, 40%) by 1H/13C-NMR and Mass spectrometric method.
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 0 - 20℃;

Reference： [1]Balachandra, Chenikkayala; Sharma, Nagendra K. [Tetrahedron, 2014, vol. 70, # 41, p. 7464 - 7469]
[2]Balachandra, Chenikkayala; Sharma, Nagendra K. [Organic Letters, 2015, vol. 17, # 16, p. 3948 - 3951]

38
[ 591-50-4 ]
[ 2577-46-0 ]
[ 1224466-99-2 ]

Yield	Reaction Conditions	Operation in experiment
78%	With copper(l) iodide; 2-(2-methyl-1-oxopropane)cyclohexanone; caesium carbonate In N,N-dimethyl-formamide at 20℃; for 8h; Inert atmosphere;

Reference： [1]Sharma, Krishna K.; Sharma, Swagat; Kudwal, Anurag; Jain, Rahul [Organic and Biomolecular Chemistry, 2015, vol. 13, # 16, p. 4637 - 4641]

39
[ 2577-46-0 ]
[ 112-05-0 ]
methyl 2-(nonanoylamino)-3-methylpentanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: nonanoic acid With 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; for 2h; Inert atmosphere; Stage #2: L-isoleucine methyl ester In tetrahydrofuran at 20℃; Inert atmosphere;	3.2.5. Methyl 2-(Nonanoylamino)propanoate (N-Nonanoyl Alanine Methyl Ester) General procedure: Amide coupling was performed according to the method of Staab [46] and Staab et al. [47] using carbonyl diimidazole (CDI). To a stirred solution of nonanoic acid (322.9 μL, 2 mmol) in anhydrous THF (4.39 mL) under N2 was added CDI (324.3 mg, 2 mmol), causing effervescence from liberated CO2. Stirring was continued at room temperature for 2 h and methyl L-alaninate (279.2 mg, 2 mmol) was added, resulting in separation of a brown oily residue. Stirring at room temperature continued overnight, by which time a white precipitate had formed. The solvent was removed in vacuo, resulting in the formation of white crystals in an oily residue, which were then taken up in Et2O (10 mL), EtOAc (20 mL), and H2SO4 (1 M, 15 mL). The phases were separated and the organic phase was washed successively with H2SO4 (1 M, 3 × 15 mL), water (20 mL), and brine (20 mL). The organic phase was dried (MgSO4), filtered, and concentrated in vacuo, producing a white crystalline solid, (551.3 mg, 2.27 mmol, 113%) which was used crude in the subsequent reaction. A small portion was purified for characterisation by column chromatography on silica (80% CH2Cl2/EtOAc, Rf = 0.51) to give the title compound as a pale yellow powder, which was 98% pure (HPLC-MS),

Reference： [1]Boss, Paul K.; Pearce, Anthony D.; Zhao, Yanjia; Nicholson, Emily L.; Dennis, Eric G.; Jeffery, David W. [Molecules, 2015, vol. 20, # 5, p. 7845 - 7873]

40
[ 143-07-7 ]
[ 2577-46-0 ]
methyl 2-(dodecanoylamino)-3-methylpentanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: lauric acid With 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; for 2h; Inert atmosphere; Stage #2: L-isoleucine methyl ester In tetrahydrofuran at 20℃; Inert atmosphere;	3.2.5. Methyl 2-(Nonanoylamino)propanoate (N-Nonanoyl Alanine Methyl Ester) General procedure: Amide coupling was performed according to the method of Staab [46] and Staab et al. [47] using carbonyl diimidazole (CDI). To a stirred solution of nonanoic acid (322.9 μL, 2 mmol) in anhydrous THF (4.39 mL) under N2 was added CDI (324.3 mg, 2 mmol), causing effervescence from liberated CO2. Stirring was continued at room temperature for 2 h and methyl L-alaninate (279.2 mg, 2 mmol) was added, resulting in separation of a brown oily residue. Stirring at room temperature continued overnight, by which time a white precipitate had formed. The solvent was removed in vacuo, resulting in the formation of white crystals in an oily residue, which were then taken up in Et2O (10 mL), EtOAc (20 mL), and H2SO4 (1 M, 15 mL). The phases were separated and the organic phase was washed successively with H2SO4 (1 M, 3 × 15 mL), water (20 mL), and brine (20 mL). The organic phase was dried (MgSO4), filtered, and concentrated in vacuo, producing a white crystalline solid, (551.3 mg, 2.27 mmol, 113%) which was used crude in the subsequent reaction. A small portion was purified for characterisation by column chromatography on silica (80% CH2Cl2/EtOAc, Rf = 0.51) to give the title compound as a pale yellow powder, which was 98% pure (HPLC-MS),

Reference： [1]Boss, Paul K.; Pearce, Anthony D.; Zhao, Yanjia; Nicholson, Emily L.; Dennis, Eric G.; Jeffery, David W. [Molecules, 2015, vol. 20, # 5, p. 7845 - 7873]

41
[ 2577-46-0 ]
[ 1480-30-4 ]
N-trifluoroacetyl-L-leucyl-L-isoleucine methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With dicyclohexyl-carbodiimide In tetrahydrofuran at 0℃; for 36h;	N-Trifluoroacetyl-L-leucyl-L-isoleucine methylester (7) General procedure: To a solution of 11.36 g (50 mmol) of N-trifluoroacetyl-L-leucine in 100 mL of THF cooled to 0 °C at vigorous stirring were added in succession solutions of 10.3 g (50 mmol) of dicyclohexylcarbodiimide in 70 mL of THF and 7.99 g (55 mmol) of L-isoleucine methyl ester in 50 mL of THF. The reaction mixture was stirred for 36 h, filtered, and the solvent was removed at a reduced pressure. The residue was washed with hexane, dissolved in ethyl ether, the solution obtained was filtered, the solvent was removed at a reduced pressure, residue was washed with hexane and dried in a vacuum. Yield 13.46 g (76%), mp 134-135 °C, [α]D20 -48.5° (c 2.5, MeOH). IR spectrum, ν, cm-1: 1754, 1718, 1663 (C=O), 1563, 1547 (N-Hamide). 1H NMR spectrum (CDCl3), δ, ppm: 0.77-0.86 m (12H, 4CH3), 1.05-1.15 m (1H, CH), 1.55-1.65 m (4H, 2CH2), 1.76-1.82 m (1H, CH), 3.66 s (3H, CH3), 4.44-4.48 m (1H, CH), 4.67-4.72 m (1H, CH). 13C NMR spectrum (CDCl3), δ, ppm: 11.27, 15.13, 21.84, 22.52, 24.56, 25.01, 37.46, 40.92, 51.95, 52.14, 56.76, 115.71 q (JC-F 228.5 Hz), 157.24 q (J 31.7 Hz), 171.29, 171.86. Found, %: C 50.63; H 7.38; N 7.81. C15H25F3N2O4. Calculated, %: C 50.84; H 7.11; N 7.91.

Reference： [1]Gaidukevich; Popova; Zubreichuk; Knizhnikov [Russian Journal of Organic Chemistry, 2015, vol. 51, # 5, p. 615 - 618][Zh. Org. Khim., 2015, vol. 51, # 5, p. 637 - 640,4]

42
[ 2577-46-0 ]
[ 1480-30-4 ]
[ 36077-41-5 ]

Reference： [1]Russian Journal of Organic Chemistry,2015,vol. 51,p. 615 - 618
Zh. Org. Khim.,2015,vol. 51,p. 637 - 640,4

43
[ 2577-46-0 ]
[ 82911-69-1 ]
N-(9-fluorenylmethoxycarbonyl)isoleucine methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With sodium hydrogencarbonate; 1-butyl-3-methylimidazolium Tetrafluoroborate In water at 25℃; for 0.133333h;

Reference： [1]Di Gioia; Gagliardi; Leggio; Leotta; Romio; Liguori [RSC Advances, 2015, vol. 5, # 78, p. 63407 - 63420]

44
[ 13139-17-8 ]
[ 2577-46-0 ]
[ 42807-91-0 ]

Yield	Reaction Conditions	Operation in experiment
88%	With sodium hydrogencarbonate; 1-butyl-3-methylimidazolium Tetrafluoroborate In water at 25℃; for 0.133333h;

Reference： [1]Di Gioia; Gagliardi; Leggio; Leotta; Romio; Liguori [RSC Advances, 2015, vol. 5, # 78, p. 63407 - 63420]

45
[ 2577-46-0 ]
[ 30992-29-1 ]
Boc-Aib-Ile-OMe [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2.92 g	With dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃; for 12h;	Boc-Aib-Ile-OMe (2) The IleOMe obtained from its hydrochloride (4.47 g, 24.63 mmol) was added to an ice-cooled solution of Boc-Aib-OH (2 g, 9.85 mmol) in 5 ml of DCM. Then DCC(3.04 g, 14.78 mmol) was added to the cooled mixture, which was stirred for 12 h at room temperature. The progress of the reaction was monitored by TLC. The residue was then taken into ethyl acetate and the DCU (N,N-dicyclohexylurea) was filtered off. The organic layer was washed with 2M HCl (3 x 100 mL), 1M sodium carbonate (3 x 100 mL) and brine (2 x 100 mL), dried over anhydrous sodium sulfate and evaporated in vacuo to obtain a white solid. The crude peptide was synthesized following similar procedure as that of dipeptide 1.

Reference： [1]Sharma, Ankita; Goswami, Soumyabrata; Rajagopalan; Konar, Anita Dutt [Supramolecular Chemistry, 2015, vol. 27, # 10, p. 669 - 678]

46
[ 2577-46-0 ]
2,3,4,5-tetra-O-acetyl-D-glucopyranose [ No CAS ]
[ 24424-99-5 ]
N-(2,3,4,6-tetra-O-acetyl-α/β-D-glucopyranosyloxycarbonyl)-L-isoleucine methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	Stage #1: L-isoleucine methyl ester; di-<i>tert</i>-butyl dicarbonate With dmap In dichloromethane for 1h; Cooling with ice; Stage #2: 2,3,4,5-tetra-O-acetyl-D-glucopyranose In dichloromethane for 18h; Cooling with ice;	9.1 (1) 4Ac-Glc-Ile-OMe; N-(2,3,4,6-tetra-O-acetyl-α/β-D-glucopyranosyloxycarbonyl)-L-isoleucine methyl ester L-isoleucine methyl ester hydrochloride (3.00 g, 16.5 mmol) was suspended in tetrahydrofuran (33 ml), and the suspension was cooled in an ice bath. To this suspension was added triethylamine (46.0 ml, 330 mmol), and the mixture was warmed to room temperature and stirred for 1 hr. The reaction solution was filtered, and concentrated to give L-isoleucine methyl ester (2.13 g, 14.7 mmol). (0234) BocO (4.48 g, 20.5 mmol) was dissolved in dichloromethane (69 ml), and the mixture was cooled in an ice bath. To this solution was added a solution of 4-(dimethylamino)pyridine (1.97 g, 16.1 mmol) in dichloromethane (69 ml) and a solution of L-isoleucine methyl ester (2.13 g, 20.5 mmol) in dichloromethane (69 ml), and the mixture was stirred at room temperature for 1 hr. The reaction solution was cooled again in an ice bath, a solution of 2,3,4,6-tetra-O-acetyl-D-glucose (7.17 g, 20.5 mmol) in dichloromethane (69 ml) was added, and the mixture was stirred for 18 hr. The reaction solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (gradient; hexane:ethyl acetate=82:18→50:50) to give 4Ac-Glc-Ile-OMe (5.72 g, 11.0 mmol, yield 75%, α:β ratio=1:1) as a white syrup-like substance. (0235) 1H-NMR (400 MHz, CDCl3) δ: 0.89-0.95(t, 6H, J=7.0 Hz), 1.13-1.27(m, 1H), 1.37-1.46(m, 1H), 1.86-1.94(m, 1H), 2.01-2.09(m, 12H), 3.73(s, 1.5H), 3.76(s, 1.5H), 3.80-3.84(m, 0.5H), 4.07-4.14(m, 1.5H), 4.25-4.36(m, 2H), 5.08-5.17(m, 2H), 5.25(t, 0.5H, J=5.2 Hz), 5.41(dd, 1H, J=5.4, 9.1 Hz), 5.47(t, 0.5H, J=5.5 Hz), 5.65(d, 0.5H, J=8.3 Hz), 6.24(d, 0.5H, J=3.7 Hz). (0236) ESIMS (m/z): 542.2 ([M+Na]+), 558.1 ([M+K]+).

Reference： [1]Current Patent Assignee: AJINOMOTO COMPANY INC - US2016/200755, 2016, A1 Location in patent: Page/Page column 11; 12

47
[ 2577-46-0 ]
[ 26893-73-2 ]
(2S,3S)-methyl 2-(6-methoxypicolinamido)-3-methylpentanoate [ No CAS ]