Name: 153-94-6|H-D-Trp-OH|97%
Brand: Ambeed
SKU: A101619
Price: 5.0 USD
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1
[ 2280-01-5 ]
[ 153-94-6 ]

Reference： [1]Journal of the American Chemical Society,1949,vol. 71,p. 3251
[2]Journal of Biological Chemistry,1933,vol. 100,p. 79,82
[3]Journal of Biological Chemistry,1932,vol. 98,p. 565,571
[4]Phytochemistry,2009,vol. 70,p. 1129 - 1138

2
[ 2279-15-4 ]
[ 153-94-6 ]

Reference： [1]Journal of Biological Chemistry,1949,vol. 179,p. 815,817

3
[ 54-12-6 ]
[ 153-94-6 ]

Yield	Reaction Conditions	Operation in experiment
48%	With sodium hydroxide; oxygen; 2-amino-2-hydroxymethyl-1,3-propanediol In water at 30℃; for 8h; Resolution of racemate; Enzymatic reaction; enantioselective reaction;
82 % Chromat.	With borane-ammonia complex; oxygen; ammonium formate In water for 5h;
	Multi-step reaction with 3 steps 1: HCl 2: beim Behandeln mit Pankreas-Enzym in wss. Loesung 3: Ba(OH)2; methanol

	With β-cyclodextrin modified Fe₃O₄ nanoparticles Magnet separation; Resolution of racemate; enantioselective reaction;
~ 100 % ee	With bovine serum albumin modified silica nanoparticles using polydopamine In aq. phosphate buffer for 0.166667h; Sonication; enantioselective reaction;
>99 % ee	With (2R)-aspartic acid In methanol; aq. phosphate buffer at 37℃; for 6h; Enzymatic reaction;
> 99 % ee	With borane-ammonia complex; ancestral L-amino acid oxidase at 30℃; for 24h; Enzymatic reaction;

Reference： [1]Location in patent: body text Zhang, Zizhang [Tetrahedron Letters, 2008, vol. 49, # 45, p. 6468 - 6470]
[2]Chen, Yun; Shiao, Ming-Tang [Bulletin of the Chemical Society of Japan, 1992, vol. 65, # 12, p. 3423 - 3429]
[3]Alexandre, François-René; Pantaleone, David P.; Taylor, Paul P.; Fotheringham, Ian G.; Ager, David J.; Turner, Nicholas J. [Tetrahedron Letters, 2002, vol. 43, # 4, p. 707 - 710]
[4]Brenner et al. [Helvetica Chimica Acta, 1948, vol. 31, p. 1908,1910]
[5]Location in patent: scheme or table Chen, Xin; Rao, Jinan; Wang, Jin; Gooding, J. Justin; Zou, Gang; Zhang, Qijin [Chemical Communications, 2011, vol. 47, # 37, p. 10317 - 10319]
[6]Li, Wei; Ding, Guo-Sheng; Tang, An-Na [RSC Advances, 2015, vol. 5, # 114, p. 93850 - 93857]
[7]Parmeggiani, Fabio; Rué Casamajo, Arnau; Walton, Curtis J. W.; Galman, James L.; Turner, Nicholas J.; Chica, Roberto A. [ACS Catalysis, 2019, vol. 9, # 4, p. 3482 - 3486]
[8]Nakano, Shogo; Minamino, Yuki; Hasebe, Fumihito; Ito, Sohei [ACS Catalysis, 2019, vol. 9, # 11, p. 10152 - 10158]

4
[ 67-56-1 ]
[ 153-94-6 ]
(R)-(+)-tryptophan methyl ester hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With thionyl chloride for 4h; Heating;
98%	With thionyl chloride at 0 - 40℃; for 6h;	3 Synthesis of methyl esters of L- and D-tryptophanes chlorohydrates; :1a,b 2a,b a : D b : L[0344] Thionylchloride (0.064 mol) was slowly added to a cooled (O0C) suspension of tryptophane (0.049 mol) in methanol (150 mL). The reaction mixture was warmed up to 4O0C and stirred at this temperature for six hours. All solvents were removed and the solid residue was triturated with ether. The solid was filtered off to give the required product.[0345] D-tryptophane (2a): yield 98 %, M.p. 232-233°C. NMR1H (δ, ppm,DMSO-dθ, 300 MHz): 3.39 (2H, m, CH2); 3.63 (3H, s, CH3O); 4.20 (1 H1 t, CH, JHH = 5.5 Hz); 7.07 (2H, dt, Ar, JHH = 21 Hz, 6 Hz); 7.26 (1 H, d, H2, JHH = 3 Hz); 7.39 (1 H, d, Ar, JHH = 7.8 Hz); 7.53 (1 H, d, Ar, JHH = 7.8 Hz). NMR13C (δ, ppm, DMSO-d6, 125.76 MHz): 26.01 (s), 52.61 (d), 106.26(s), 111.45(s), 117.84(s), 118.50(s), 121.05(s), 124.80(s), 126.79(s), 136.13(s), 169.57(s). m/z 218(M+).
97%	With thionyl chloride at 40℃; for 4h;

95%	With thionyl chloride at 0 - 20℃; for 15h;
95%	With thionyl chloride In toluene at 0 - 80℃; for 4h;	1 Preparation of D-tryptophan methyl ester hydrochloride D-tryptophan (50 g) was added to a mixed solution of toluene (650 ml) and methanol (105 ml)Slowly drop at 0 degrees CelsiusPlus thionyl chloride (38.6 g),After the dropwise addition, the temperature was raised to 75 to 80 ° C. After the reaction was refluxed for 4 hours,The reaction ends,The reaction solution was cooled to 0 ° C and stirred for 2 hours,Precipitation of solids,filter,The filter cake was washed with toluene,Dried at 50 ° C for 6 h,To obtain D-tryptophan methyl ester hydrochloride,White powder solid.Yield 95%HPLC purity 99%.
93%	With thionyl chloride at -10 - 37℃; for 6h;
92.4%	With thionyl chloride In methanol for 1 - 2h; Heating / reflux;
92%	With thionyl chloride at -10 - 25℃; for 6.5h;
86%	With thionyl chloride for 24h; Reflux;
86%	With thionyl chloride for 24h; Reflux;	2a Synthesis Example 2a-(2R)-3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-aminium chloride Thionyl chloride (9.87 mmol, 0.72 mL) was added dropwise to a solution of D-tryptophan (1.000 g, 4.89 mmol) in methanol (33 mL). The reaction was heated to reflux with vigorous stirring for 24 h. After cooling, the reaction mixture was concentrated under reduced pressure and residual methanol traces removed by azeotropic distillation with dichloromethane (10 mL) under reduced pressure to give the title compound as a white solid (1.070 g, 86%). [0401] 1H NMR (500 MHz, D2O) δ=7.52 (1H, d, J=7.9, 9-H), 7.46 (1H, d, J=8.1, 12-H), 7.26-7.10 (3H, m, 4, 5, 9-H), 4.37 (1H, t, J=6.0, 2-H), 3.73 (3H, s, β-H), 3.44-3.31 (2H, m, 4-H). [0402] 13C NMR (126 MHz, D2O) δ=170.4 (2-C), 136.3 (7-C), 126.4 (8-C), 125.4 (6-C), 122.3 (11-CH), 119.6 (10-CH), 118.1 (9-CH), 112.1 (12-CH), 106.0 (5-C), 53.6 (13-CH3), 53.3 (2-CH), 25.7 (4-CH2). [0403] IR (diamond, vMAX, cm-1) 3261 (NH st), 2870 (N+-H st), 2023 (Ar comb), 1748 (C═O st), 1229, 1211 (CO-O st as), 1181 (C-O st as). [0404] Acc. Mass (FAB): C12H15N2O2 Found: 219.1120 m/z Calculated: 219.1128 m/z.
80%	With thionyl chloride at 25 - 30℃; for 3 - 4h; Heating / reflux;	1 D-tryptophan (100 g) was suspended in methanol (500 mL) and the suspension added to a solution of thionyl chloride (82.14 g) in methanol (500 mL) at 25-30° C under nitrogen atmosphere. The resultant solution was stirred at reflux for 3 to 4 hours and the reaction mixture was concentrated to a residual volume of 150 mL. To the concentrated mixture dichloromethane (700 mL) was added and the resultant solution was cooled to 0- 5° C with continuous stirring for 0.5 hours. The solid so obtained was filtered, washed with dichloromethane (200 mL) and dried in air at 40-45° C to afford D-tryptophan methyl ester hydrochloride.Yield: 10O g (80%)
68%	Stage #1: methanol; D-tryptophan With p-toluenesulfonyl chloride at 65℃; for 12h; Stage #2: With hydrogenchloride In water	2 Example 2 A method for preparing D-tryptophan methyl ester hydrochloride includes the following steps:In a 250mL flask, 2.000g of p-toluenesulfonyl chloride and 50mL of methanol were added. After stirring, 2.000g of D-tryptophan and 60mL of methanol were added, and the mixture was heated to 65 ° C under reflux for 12 hours. The methanol was removed by rotary evaporation to obtain crude tryptophan methyl ester hydrochloride .The crude product was mixed with dichloromethane, stirred to add an aqueous solution of sodium bicarbonate, adjusted to pH = 8, the product was extracted 3 times with dichloromethane, the organic phases were combined, and 10% hydrochloric acid by mass was added dropwise to the organic phase until turbidity appeared Then, continue to add hydrochloric acid dropwise, the total amount of hydrochloric acid is 8mL.After filtration, 0.866 g of D-tryptophan methyl ester hydrochloride as a white solid was obtained in a yield of 68%.The HPLC purity of the product was 96.78% (area normalization method).
	With thionyl chloride for 18h; Heating; Yield given;
	Stage #1: methanol With thionyl chloride at 0℃; for 0.5h; Stage #2: D-tryptophan Heating;
	With hydrogenchloride for 3.5h; Heating;
	With acetyl chloride Reflux;
	Stage #1: methanol With thionyl chloride at 0℃; for 0.5h; Stage #2: D-tryptophan at 60℃; for 18h;
	Stage #1: methanol With thionyl chloride at 0℃; for 0.5h; Inert atmosphere; Stage #2: D-tryptophan at 20℃; Inert atmosphere;	4.1.2 General procedure for syntheses of compounds 4a-4f General procedure: To 4mL of ice-bath cooled methanol was added drop-wise 1mL of thionyl chloride in 5min under nitrogen, the resulting mixture was stirred for 0.5h and amine derivatives 3a-3f were added. The reaction mixture was stirred at room temperature overnight until complete disappearance of the materials indicated by TLC. The solvent and the surplus SOCl2 were removed in vacuum. The residue was dissolved in 20mL of methanol and evaporated under reduced pressure. The procedure was repeated for three times. Then 20mL of ether was added to the residue and evaporated in vacuum, which also took three times. Target compounds 4a-4f were obtained in 86%-95% yield and used without further purification for the following step.
	With thionyl chloride at 0 - 68℃; for 1.5h;	2.1 Thionyl chloride (SOCl2; 2.4 ml) is added to a suspension of D-tryptophan (3g; 14.7 mmoles) in 20 ml methanol, stirring under nitrogen atmosphere in ice bath. The solution is then refluxed (~68°C) for 1.5 hour. Methanol is evaporated and 20 ml of tert-butyl- methyl ether (MTBE) are added. The solution is stirred in ice bath for 1 hour, then it is filtered and the product is washed with cold MTBE. The obtained white solid is dried under vacuum at 600C.
	With thionyl chloride at 0 - 20℃;
	With thionyl chloride at 0 - 20℃; for 3h; Reflux;
	With thionyl chloride at 65℃; for 1h;	1-4; 1 Preparation of Intermediate II Put 1.8L methanol into the reaction kettle, add 361g starting material 1, add 2.65mol thionyl chloride dropwise under the condition of 20±5, after dripping, heat to reflux 65±3°C and react for 1h, monitor the start After the reaction of raw material 1 is completed, the solvent is evaporated under reduced pressure, then 1.8L isopropanol, 265g piperonal are added, stirred and heated to reflux for 7h, the mixture is cooled to 10±5°C, stirred and crystallized for 2h, centrifuged, and dried in vacuum to obtain Solid powder intermediate II 596g, yield 87.2%, purity 99.10%, no isomer impurities were detected.

Reference： [1]Appleton, David R; Babcock, Russell C; Copp, Brent R [Tetrahedron, 2001, vol. 57, # 51, p. 10181 - 10189]
[2]Current Patent Assignee: COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK - WO2008/103470, 2008, A2 Location in patent: Page/Page column 106
[3]Earle, Martyn J.; Noe, Marco; Perosa, Alvise; Seddon, Kenneth R. [RSC Advances, 2014, vol. 4, # 3, p. 1204 - 1211]
[4]Fujiwara, Tomoya; Yasuda, Hiroko; Nishimura, Yushi; Nambu, Hisanori; Yakura, Takayuki [RSC Advances, 2015, vol. 5, # 7, p. 5464 - 5473]
[5]Current Patent Assignee: SHENZHEN DONGYANGGUANG INDUSTRIAL DEVELOPMENT CO LTD - CN104557920, 2016, B Location in patent: Paragraph 0026; 0027
[6]Bhunia, Shome S.; Misra, Ankita; Khan, Imran A.; Gaur, Stuti; Jain, Manish; Singh, Surendra; Saxena, Aaruni; Hohlfield, Thomas; Dikshit, Madhu; Saxena, Anil K. [Journal of Medicinal Chemistry, 2017, vol. 60, # 1, p. 322 - 337]
[7]Current Patent Assignee: ELI LILLY & CO - WO2004/11463, 2004, A1 Location in patent: Page 19
[8]Gupta, Amit K.; Varshney, Kanika; Singh, Neetu; Mishra, Vaibhav; Saxena, Mridula; Palit, Gautam; Saxena, Anil K. [Journal of Chemical Information and Modeling, 2013, vol. 53, # 1, p. 176 - 187]
[9]Newcombe, Sonya; Bobin, Mariusz; Shrikhande, Amruta; Gallop, Chris; Pace, Yannick; Yong, Helen; Gates, Rebecca; Chaudhuri, Shuvashri; Roe, Mark; Hoffmann, Eva; Viseux, Eddy M. E. [Organic and Biomolecular Chemistry, 2013, vol. 11, # 19, p. 3255 - 3260]
[10]Current Patent Assignee: UNIVERSITY OF SUSSEX - US2014/39200, 2014, A1 Location in patent: Paragraph 0400-0404
[11]Current Patent Assignee: SUN PHARMACEUTICAL INDUSTRIES LIMITED - WO2009/4557, 2009, A2 Location in patent: Page/Page column 8
[12]Current Patent Assignee: ZHUHAI COLLEGE OF JILIN UNIVERSITY - CN110483363, 2019, A Location in patent: Paragraph 0041-0044
[13]Hvidt, Torsten; Szarek, Walter A.; Maclean, David B. [Canadian Journal of Chemistry, 1988, vol. 66, p. 779 - 782]
[14]McGuigan, Christopher; Hassan-Abdallah, Alshaimaa; Srinivasan, Sheila; Wang, Yikang; Siddiqui, Adam; Daluge, Susan M.; Gudmundsson, Kristjan S.; Zhou, Huiqiang; McLean, Ed W.; Peckham, Jennifer P.; Burnette, Thimysta C.; Marr, Harry; Hazen, Richard; Condreay, Lynn D.; Johnson, Lance; Balzarini, Jan [Journal of Medicinal Chemistry, 2006, vol. 49, # 24, p. 7215 - 7226]
[15]Yu, Peng; Wang, Tao; Li, Jin; Cook, James M. [Journal of Organic Chemistry, 2000, vol. 65, # 10, p. 3173 - 3191]
[16]Incerti, Matteo; Tognolini, Massimiliano; Russo, Simonetta; Pala, Daniele; Giorgio, Carmine; Hassan-Mohamed, Iftiin; Noberini, Roberta; Pasquale, Elena B.; Vicini, Paola; Piersanti, Silvia; Rivara, Silvia; Barocelli, Elisabetta; Mor, Marco; Lodola, Alessio [Journal of Medicinal Chemistry, 2013, vol. 56, # 7, p. 2936 - 2947]
[17]Alqahtani, Norah; Porwal, Suheel K.; James, Elle D.; Bis, Dana M.; Karty, Jonathan A.; Lane, Amy L.; Viswanathan, Rajesh [Organic and Biomolecular Chemistry, 2015, vol. 13, # 26, p. 7177 - 7192]
[18]Tang, Hong-Jin; Zhang, Xiao-Wei; Yang, Lin; Li, Wei; Li, Jia-Huang; Wang, Jin-Xin; Chen, Jun [European Journal of Medicinal Chemistry, 2016, vol. 124, p. 637 - 648]
[19]Current Patent Assignee: C T G PHARMA - WO2009/37556, 2009, A1 Location in patent: Page/Page column 25
[20]Yen, Andy; Pham, Anh Hoang; Larin, Egor M.; Lautens, Mark [Organic Letters, 2019, vol. 21, # 18, p. 7549 - 7553]
[21]Matam, Sivakumar; Kaliyan, Prabakaran; Selvaraj, Loganathan; Muthu, Seenivasa Perumal; Lohanathan, Bharathi Priya; Viswanadhan, Vijaya Padma; Makala, Himesh; Venkatasubramanian, Ulaganathan [Journal of Heterocyclic Chemistry, 2021, vol. 58, # 2, p. 569 - 579]
[22]Current Patent Assignee: LUOXIN PHARMACEUTICALS GROUP STOCK CO LTD - CN113582992, 2021, A Location in patent: Paragraph 0016; 0026-0040

5
[ 501-53-1 ]
[ 153-94-6 ]
[ 2279-15-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water; at 0 - 20℃;	General procedure: L-Tryptophan (10.24 g, 50 mmol) was dissolved in 1M NaOH (50 mL) and stirred at 0C. Benzyl chloroformate (7.15 mL, 50.1 mmol) and 1M NaOH (50 mL) where then simultaneously added in drop-wise fashion. The mixture was stirred for 1 hour at room temperature. The solution was acidified with 6M HCl to pH 1 after which the product was extracted with EtOAc (3x 200 mL). The organic layers were combined, dried by Na2SO4 and evaporated. The product was obtained a yellow solid and used directly in the following step.

Reference： [1]Journal of Organic Chemistry,2015,vol. 80,p. 8046 - 8054
[2]Organic and Biomolecular Chemistry,2004,vol. 2,p. 2415 - 2417
[3]Journal of the American Chemical Society,1984,vol. 106,p. 7506 - 7513
[4]Tetrahedron Letters,2012,vol. 53,p. 6430 - 6432
[5]Organic and Biomolecular Chemistry,2015,vol. 13,p. 7177 - 7192

6
[ 830-03-5 ]
[ 153-94-6 ]
[ 100-02-7 ]
[ 2280-01-5 ]

Reference： [1]Canadian Journal of Chemistry,1991,vol. 69,p. 1124 - 1130

7
H-Arg-D-Trp-N^mePhe-D-Trp-Leu-Met-NH₂ [ No CAS ]
[ 74-79-3 ]
[ 2566-30-5 ]
[ 153-94-6 ]

Reference： [1]Analytical Chemistry,1995,vol. 67,p. 4431 - 4436

8
[ 188346-51-2 ]
[ 153-94-6 ]
N-<(1,1-dimethylethoxy)carbonyl>-2,2-dimethyl-β-alanyl-(2S)-2-hydroxy-4-(methylpentanoyl)-(2E,5S,6R,7E)-5-hydroxy-6-methyl-8-phenyl-2,7-octadienoyl-D-tryptophan [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With N,O-bis-(trimethylsilyl)-acetamide In N,N-dimethyl-formamide at 55 - 60℃;

Reference： [1]Patel, Vinod F.; Andis, Sherri L.; Kennedy, Joseph H.; Ray, James E.; Schultz, Richard M. [Journal of Medicinal Chemistry, 1999, vol. 42, # 14, p. 2588 - 2603]

9
[ 503-74-2 ]
[ 1783-96-6 ]
Fmoc-Lys(Mtt)-OH [ No CAS ]
[ 153-94-6 ]
isobutylcarbonyl [ No CAS ]
(R)-2-[(R)-2-((S)-6-Amino-2-isobutyrylamino-hexanoylamino)-3-(1H-indol-3-yl)-propionylamino]-succinic acid 4-tert-butyl ester [ No CAS ]

Reference： [1]Tetrahedron Letters,1997,vol. 38,p. 1191 - 1194

10
[ 56-87-1 ]
[ 71989-14-5 ]
[ 153-94-6 ]
tert-butyloxycarbonyl [ No CAS ]
Boc-Lys-D-Trp-D-Asp(OtBu)-OH [ No CAS ]

Reference： [1]Tetrahedron Letters,1997,vol. 38,p. 1191 - 1194

11
[ 923-27-3 ]
[ 71989-14-5 ]
[ 153-94-6 ]
tert-butyloxycarbonyl [ No CAS ]
Boc-D-Lys-D-Trp-D-Asp(OtBu)-OH [ No CAS ]

Reference： [1]Tetrahedron Letters,1997,vol. 38,p. 1191 - 1194

12
[ 67-63-0 ]
[ 153-94-6 ]
D-tryptophan isopropyl ester hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With thionyl chloride at 0℃; Reflux;
	With hydrogenchloride
	With hydrogenchloride

With hydrogenchloride at 50℃; for 72h;

2 Example 2 The Preparation of D-Tryptophan Isopropyl Ester.HCl Example 2 The Preparation of D-Tryptophan Isopropyl Ester.HCl [0101] D-Tryptophan (1 kg) was suspended in isopropanol (5 L) in a 10 L flask. HCl gas (350 g) was bubbled into the reaction mixture. The mixture was stirred for 2 days at 50° C. The solvent was evaporated off at below 40° C., and fresh isopropanol (4 L) was added into the residue. The mixture was stirred for 1 day at 50° C. The solvent was evaporated off at below 40° C., and isopropyl acetate (3 L) was added into the residue. The solid was collected by filtration and washed with isopropyl acetate (3×1 L). The solid was dried in a vacuum oven at 50° C.

Reference： [1]Zeng, Debin; Zhang, Rui; Nie, Quandeng; Cao, Lin; Shang, Luqing; Yin, Zheng [ACS Medicinal Chemistry Letters, 2016, vol. 7, # 12, p. 1197 - 1201]
[2]Shizuma, Motohiro; Adachi, Hiroshi; Amemura, Akinori; Takai, Yoshio; Takeda, Tokuji; Sawada, Masami [Tetrahedron, 2001, vol. 57, # 21, p. 4567 - 4578]
[3]Location in patent: experimental part Shizuma, Motohiro; Kiso, Taro; Terauchi, Hisashi; Takai, Yoshio; Yamada, Hitoshi; Nishimoto, Tomoyuki; Ono, Daisuke; Shimomura, Osarnu; Nomura, Ryoki; Miwa, Yoshikatsu; Nakamura, Masaki; Nakano, Hirofumi [Chemistry Letters, 2008, vol. 37, # 10, p. 1054 - 1055]
[4]Current Patent Assignee: SPRAYABLE HOLDINGS - US2014/256749, 2014, A1 Location in patent: Paragraph 0101

13
[ 2418-95-3 ]
[ 2799-07-7 ]
[ 4727-00-8 ]
[ 108-24-7 ]
[ 153-94-6 ]
Cys-Phe-resin [ No CAS ]
AcCFwKYCNH₂ [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2002,vol. 41,p. 2940 - 2944

14
[ 64-18-6 ]
[ 153-94-6 ]
(R)-4,9-dihydro-3H-pyrido[3,4-b]indole-3-carboxylic acid hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With hydrogenchloride; acetic anhydride
60%	Stage #1: formic acid; D-tryptophan With acetic anhydride Stage #2: With hydrogenchloride; formic acid Further stages.;
59%	Stage #1: formic acid; D-tryptophan With acetic anhydride at 20℃; for 1.5h; Stage #2: With hydrogenchloride at 55℃; for 2.5h;

59%	Stage #1: formic acid; D-tryptophan With acetic acid at 20℃; for 1.5h; Stage #2: With hydrogenchloride In water at 55℃; for 2.5h;
59%	Stage #1: formic acid; D-tryptophan With acetic anhydride at 20℃; for 1.5h; Stage #2: With hydrogenchloride In water at 55℃; for 2.5h;

Reference： [1]Deiters, Alexander; Chen, Kevin; Eary, C. Todd; Martin, Stephen F. [Journal of the American Chemical Society, 2003, vol. 125, # 15, p. 4541 - 4550]
[2]Martin, Stephen F.; Chen, Kevin X.; Eary, C. Todd [Organic Letters, 1999, vol. 1, # 1, p. 79 - 81]
[3]Jarret, Maxime; Tap, Aurélien; Kouklovsky, Cyrille; Poupon, Erwan; Evanno, Laurent; Vincent, Guillaume [Angewandte Chemie - International Edition, 2018, vol. 57, # 38, p. 12294 - 12298][Angew. Chem., 2018, vol. 130, # 38, p. 12474 - 12478,5]
[4]Jarret, Maxime; Turpin, Victor; Tap, Aurélien; Gallard, Jean-François; Kouklovsky, Cyrille; Poupon, Erwan; Vincent, Guillaume; Evanno, Laurent [Angewandte Chemie - International Edition, 2019, vol. 58, # 29, p. 9861 - 9865][Angew. Chem., 2019, vol. 131, # 29, p. 9966 - 9970,5]
[5]Jarret, Maxime; Tap, Aurélien; Turpin, Victor; Denizot, Natacha; Kouklovsky, Cyrille; Poupon, Erwan; Evanno, Laurent; Vincent, Guillaume [European Journal of Organic Chemistry, 2020, vol. 2020, # 40, p. 6340 - 6351]

15
[ 24424-99-5 ]
[ 153-94-6 ]
[ 5241-64-5 ]

Yield	Reaction Conditions	Operation in experiment
86%	With triethylamine In methanol Inert atmosphere;	14.1.2.General Procedure for Synthesis of N-[(tert-butoxy)carbonyl]-d-tryptophan (17) The reaction mixture of d-tryptophan (14, 4.89 mmol), triethylamine (9.79 mmol) and di-tert-butyl dicarbonate (Boc2O, 6.36 mmol) was stirred in methanol (10 mL) under the nitrogen at room temperature for 24 h. After the evaporation of methanol under the pressure, the final product was isolated in 86% yield.
	With sodium hydroxide In tetrahydrofuran; water at 0℃;

Reference： [1]Chalupova, Katarina; Korabecny, Jan; Bartolini, Manuela; Monti, Barbara; Lamba, Doriano; Caliandro, Rosanna; Pesaresi, Alessandro; Brazzolotto, Xavier; Gastellier, Anne-Julie; Nachon, Florian; Pejchal, Jaroslav; Jarosova, Michaela; Hepnarova, Vendula; Jun, Daniel; Hrabinova, Martina; Dolezal, Rafael; Zdarova Karasova, Jana; Mzik, Martin; Kristofikova, Zdena; Misik, Jan; Muckova, Lubica; Jost, Petr; Soukup, Ondrej; Benkova, Marketa; Setnicka, Vladimir; Habartova, Lucie; Chvojkova, Marketa; Kleteckova, Lenka; Vales, Karel; Mezeiova, Eva; Uliassi, Elisa; Valis, Martin; Nepovimova, Eugenie; Bolognesi, Maria Laura; Kuca, Kamil [European Journal of Medicinal Chemistry, 2019, vol. 168, p. 491 - 514]
[2]Tammler, Ursula; Quillan, J. Mark; Lehmann, Jochen; Sadee, Wolfgang; Kassack, Matthias U. [European Journal of Medicinal Chemistry, 2003, vol. 38, # 5, p. 481 - 493]

16
[ 108-30-5 ]
[ 153-94-6 ]
(R)-N-[1-carboxy-2-(1H-indol-3-yl)ethyl]succinamic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	In tetrahydrofuran for 40h; Heating;
92.35%	In acetone at 50℃; for 12h;	2 Example 2 Take 3.00g (30.0mmol) succinic anhydride and 15mL acetone into a 50mL reaction bottle, stir and heat, and add D-tryptophan 2.04g (10.0mmol) to 50 °C after it is completely dissolved, and track the reaction progress by thin layer chromatography. After the end of the 12h reaction, the solvent was removed by rotational evaporation, the solid crude product was dissolved with ethyl acetate, washed several times with 0.5M sodium carbonate solution, dried with anhydrous sodium sulfate for extraction, removed by reduced pressure distillation to obtain a reddish-brown solid, and recrystallized with absolute ethanol to obtain the product, yield 92.35%, and the structural formula of the product was (I.-2).

Reference： [1]Jursic, Branko S.; Patel, Paresh K. [Tetrahedron, 2005, vol. 61, # 4, p. 919 - 926]
[2]Current Patent Assignee: CHINA AGRICULTURAL UNIVERSITY - CN113861096, 2021, A Location in patent: Paragraph 0042-0044

17
[ 100-52-7 ]
[ 153-94-6 ]
[ 246137-74-6 ]
[ 246137-75-7 ]

Yield	Reaction Conditions	Operation in experiment
	With trifluoroacetic acid In dichloromethane at 20℃; Title compound not separated from byproducts;
16.667 % de	With acetic acid at 20℃; for 3h; Overall yield = 66 percent; Overall yield = 0.38 g;	General Procedure A:Pictet-Spengler reaction using tryptophan. General procedure: To a stirring solution of the desired tryptophanenantiomer ((S)-tryptophan or (R)-tryptophan) in glacial acetic acid was addedthe desired aldehyde and the mixture either warmed to 80 °C or stirred at roomtemperature for the specified time. After cooling to room temperature (ifrequired), if no solid was visible, conc.ammonia (aq) was added until precipitation of the product occurred,which was collected by filtration, washed with water (2 × 20 mL) and dried toyield the desired product(s) as a mixture of diastereomers.

Reference： [1]Kuo, Fu-Ming; Tseng, Ming-Chung; Yen, Ya-Hew; Chu, Yen-Ho [Tetrahedron, 2004, vol. 60, # 52, p. 12075 - 12084]
[2]Barker, David; Brar, Harpreet Kaur; Eurtivong, Chatchakorn; Leung, Euphemia; Leung, Ivanhoe K. H.; Paulin, Emily K.; Pilkington, Lisa I.; Rees, Shaun; Reynisson, Jóhannes; Sharma, Nabangshu; White, Reuben M.; Xu, Chris Sun; van Rensburg, Michelle [European Journal of Medicinal Chemistry, 2019]

18
[ 75-07-0 ]
[ 153-94-6 ]
(1R,3R)-1-methyl-2,3,4,9-tetrahydropyrido[3,4‑b]Indole‑3‑carboxylic acid [ No CAS ]
(1S,3R)-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With trifluoroacetic acid In dichloromethane at 20℃; Title compound not separated from byproducts;
86.395 % de	With sulfuric acid In water at 20℃; Overall yield = 76 %;	Synthesis of (1S,3S)-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid (1)¹ General procedure: To a solution of L-tryptophan (20.00 g, 98.00 mmol) in water (500 mL) was added conc. H2SO4 (2 mL) and 40 % aqueous solution of acetaldehyde (20 mL) successively, and the mixture was stirred overnight at room temperature. The mixture was adjusted to pH = 6-7 with ammonia solution (25-28 %, w/w), the resulting white slurry was filtered, and the cake was washed with water to afford 1 as a white solid (16.70 g, 74 %).

Reference： [1]Kuo, Fu-Ming; Tseng, Ming-Chung; Yen, Ya-Hew; Chu, Yen-Ho [Tetrahedron, 2004, vol. 60, # 52, p. 12075 - 12084]
[2]Song, Hong-Jian; Liu, Yong-Xian; Liu, Yu-Xiu; Huang, Yuan-Qiong; Li, Yong-Qiang; Wang, Qing-Min [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 22, p. 5228 - 5233]

19
[ 153-94-6 ]
(2R)-2-amino-3-(1H-indol-3-yl)propan-1-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	With lithium aluminium tetrahydride In tetrahydrofuran for 15h; Inert atmosphere; Reflux;
98%	With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; Reflux;	3.2. Synthesis of (R)-Tryptophanol LiAlH4 (5 g, 134.64 mmol) was slowly added to a suspension of (D)-tryptophan (5 g, 24.48 mmol)in THF (200 mL) at 0 °C. After 30 min, the mixture was heated at reflux overnight. The resulting mixturewas cooled to 0 °C and a saturated aqueous solution of Na2SO4 was added. The suspension wasfiltered, and the filtrate extracted with EtOAc (250 mL). The aqueous phase was washed with EtOAc(3 x 100 mL), and the combined organic phases were dried, and concentrated to give (R)-tryptophanol(4.58 g, 98%).
92%	With dimethyl sulfide borane In tetrahydrofuran Reflux;

92%	With dimethylsulfide borane complex In tetrahydrofuran at 0 - 70℃; for 16h;	16; D INTERMEDIATE 16 (METHOD D) C2i?y2-Amino-3-(lH-indol-3-yr)propan- 1 -olTo a solution of (i?)-tryptophan (4.0 g, 20 mmol) in THF (100 mL) at O0C was slowly added borane-dimethylsulphide complex (5.9 mL, 1OM solution in THF, 59 mmol). The reaction mixture was heated to 7O0C for 16 h and the excess borane was quenched by the addition of methanol (10 mL) at 00C. The reaction mixture was concentrated, and the residue dissolved in EtOAc (120 mL) and washed with 20% NaOH solution (2 x 70 mL). The organic layer was then extracted into aqueous 2M HCl (2 x 100 mL). The combined acidic aqueous layers were then basified to pH 14 (addition of solid NaOH) and were re-extracted with EtOAc (2 x 150 mL). The combined organic fractions were washed with brine (70 mL), dried over MgSO4 and concentrated in vacuo to give the title compound (3.5 g, 92%) as a white solid. δH (MeOD-d3) 7.46 (IH, d, J7.9 Hz), 7.21 (IH, d, J 8.0 Hz), 6.96 (3H, m), 3.79 (IH, dd, J 11.3 and 3.6 Hz)5 3.54 (IH, dd, EPO J 11.2 and 6.2 Hz)5 3.05 (IH5 m), 2.80 (IH5 m), 2.61 (IH5 m). Note: exchangeable protons not evident in MeOD.
	Multi-step reaction with 2 steps 1: thionyl chloride / 18 h / Heating 2: 72 percent / sodium borohydride / ethanol; H₂O / 18 h / Heating
	Multi-step reaction with 2 steps 1.1: chloro-trimethyl-silane / 20 °C 1.2: 1 h / -10 °C 2.1: sodium tetrahydroborate / methanol / 20 °C
	With lithium aluminium tetrahydride
	Stage #1: D-tryptophan With sodium tetrahydroborate; iodine In tetrahydrofuran at 0℃; for 19.5h; Inert atmosphere; Reflux; Stage #2: With potassium hydroxide In tetrahydrofuran; water at 20℃; for 15h;

Reference： [1]Rannoux, Claire; Roussi, Fanny; Retailleau, Pascal; Gueritte, Francoise [Organic Letters, 2010, vol. 12, # 6, p. 1240 - 1243]
[2]Pereira, Nuno A. L.; Sureda, Francesc X.; Pérez, Maria; Amat, Mercedes; Santos, Maria M. M. [Molecules, 2016, vol. 21, # 8]
[3]Location in patent: scheme or table Alexander, Rikki; Balasundaram, Ahrani; Batchelor, Mark; Brookings, Daniel; Crepy, Karen; Crabbe, Tom; Deltent, Marie-France; Driessens, Frank; Gill, Andrew; Harris, Sue; Hutchinson, Gillian; Kulisa, Claire; Merriman, Mark; Mistry, Prakash; Parton, Ted; Turner, James; Whitcombe, Ian; Wright, Sara [Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 15, p. 4316 - 4320]
[4]Current Patent Assignee: UCB - WO2006/114606, 2006, A1 Location in patent: Page/Page column 46-47
[5]Allin, Steven M.; Thomas, Christopher I.; Doyle, Kevin; Elsegood, Mark R. J. [Journal of Organic Chemistry, 2005, vol. 70, # 1, p. 357 - 359]
[6]Hvidt, Torsten; Szarek, Walter A.; Maclean, David B. [Canadian Journal of Chemistry, 1988, vol. 66, p. 779 - 782]
[7]Samuels, Eric R.; Sevrioukova, Irina F. [Bioorganic and medicinal chemistry, 2020, vol. 28, # 6]
[8]Espadinha, Margarida; Barcherini, Valentina; Gonçalves, Lídia M.; Molins, Elies; Antunes, Alexandra M. M.; Santos, Maria M. M. [Pharmaceuticals, 2021, vol. 14, # 3]
[9]Baumann, Georg; Meckel, Tobias; Böhm, Kevin; Shih, Yung-Hsin; Dickhaut, Mirco; Reichardt, Torben; Pilakowski, Johannes; Pehl, Ulrich; Schmidt, Boris [Journal of Medicinal Chemistry, 2022, vol. 65, # 2, p. 1265 - 1282]

20
[ 67-56-1 ]
[ 153-94-6 ]
D-Tryptophan methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99.4%	With sulfuric acid for 2h; Reflux; Large scale;	1-3 Synthesis of intermediate 1 D-tryptophan (25kg, 123mol), Add 125L of methanol to a 500L reactor, Stir at room temperature, Slowly add sulfuric acid (588g, 6mol), After finishing, Heated to reflux, Incubation reaction for 2h, HPLC detection is complete, The methanol was distilled off under reduced pressure, Add 175L of ethyl acetate to beat for 2h, Centrifugation, The product is dried by double cone, 31kg of white solid The yield was 99.4% and the purity was 99.1%.
93%	Stage #1: methanol; D-tryptophan With thionyl chloride for 18h; Reflux; Stage #2: With sodium carbonate
93.6%	With thionyl chloride at 10 - 45℃; for 2h; Large scale;	1.A1 In this embodiment, step A1 is: Put 50.0kg methanol and 12.0kg D-tryptophan into the reactor,Was added dropwise to the cooled thionyl chloride 16kg after 10 ~ 20 ;After the dropwise addition, the temperature was raised to 40 to 45°C, and the reaction was stirred for 2 hours;After the reaction, the methanol was concentrated and evaporated under reduced pressure,After steaming, put 50.0kg ethyl acetate into the reaction kettle,Beat at room temperature for 1 hour, then shake and filter,After drying, 12 kg of intermediate I was obtained, purity: 99.2%, yield: 93.6%.

92%	With thionyl chloride for 18h; Reflux;
70%	With hydrogenchloride In methanol at 20℃; for 16h;
41.1%	Stage #1: methanol; D-tryptophan With thionyl chloride at 0 - 80℃; Stage #2: With sodium hydroxide In water
	With thionyl chloride
	With thionyl chloride at 20℃; for 1h;
	With thionyl chloride	C1 C1. D-Tryptophan methyl ester; The title compound can be obtained by methylesterification of D-tryptophan in methanol with the aid of thionylchloride according to standard procedures.
	With thionyl chloride
	Stage #1: methanol; D-tryptophan With thionyl chloride Stage #2: With triethylamine In tetrahydrofuran
	With acetyl chloride Reflux; Inert atmosphere;
	With thionyl chloride at 0℃; Reflux;
	With thionyl chloride Reflux;
	With acetyl chloride for 5h; Reflux;
	With ammonium hydroxide; acetyl chloride Inert atmosphere;
	Stage #1: methanol; D-tryptophan With acetyl chloride Stage #2: With ammonium hydroxide
	With hydrogenchloride
	Stage #1: methanol; D-tryptophan With acetyl chloride Stage #2: With ammonium hydroxide In water
	Stage #1: methanol; D-tryptophan With acetyl chloride for 5h; Inert atmosphere; Cooling with ice; Reflux; Stage #2: With ammonium hydroxide Inert atmosphere;
	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	1.4 Protection of the Carboxylic Function General procedure: Amino acids are protected in their carboxylic function via a methyl-, ethyl- or tert-butyl-ester using thionyl chloride as reagent and either methanol, ethanol, or tert-butanol as solvent, based the procedure described in Bioorganic & medicinal chemistry 15(14):4903-9, 2007, with the following changes: Thionyl chloride was not distilled prior to reaction; and the intermediate product was not purified via recrystallization but rather using a silica-gel 60 column, with ethyl acetate in hexane as eluent. The intermediate product is verified by 200 MHz 1H-NMR using CDCl3 as solvent.
	With thionyl chloride at 0 - 20℃; for 4h;
	With thionyl chloride In methanol at 0 - 25℃;
	With thionyl chloride at 0 - 20℃;
	With thionyl chloride at 0 - 20℃; for 12h;	1 Example 1: Synthesis of Compound F (Reaction Scheme 9): (R)-Tryptophane Methyl Ester (Compound F English Name: (R)-Methyl-2-amino -3-(1H-indol-3-yl) propanoate) In a three-necked flask equipped with mechanical stirring, add 600 mL of anhydrous methanol.D-tryptophan (102.1 g, 500 mmol), stirring at room temperature,Using an ice-salt bath, the temperature of the reaction system was reduced to 0° C. and thionyl chloride (71.4 g, 600 mmol) was added dropwise.After dropping,The temperature was raised to room temperature for about 12 hours.TLC monitoring, when the reaction of the raw materials is complete, the reaction is stopped.After most of the remaining thionyl chloride and methanol have been distilled out at atmospheric pressure, the thionyl chloride and methanol are removed under reduced pressure and cooled.The solid tryptophan methyl ester hydrochloride was obtained (air-isolated, low temperature can be stored for a longer period of time).When free tryptophan methyl ester is to be used, take a small amount of the hydrochloride of the above tryptophan methyl ester and dissolve it with chloroform.The solution was washed with a saturated solution of sodium bicarbonate until weakly alkaline, the organic layer was dried, and the solvent chloroform was removed.The resulting solid (ie, tryptophan methyl ester) is vacuum dried and, in general, does not require further purification.It can be used directly for next step asymmetric catalytic reactions. If you really need it,The tryptophan methyl ester can be recrystallized with a mixed solvent of toluene and n-hexane.The resulting recrystallized solid was vacuum dried and used for the next step asymmetric catalytic reaction.
	With thionyl chloride at 0 - 20℃; for 12h;	5 Example 5 Synthesis of Compound F (Formula 13): (R)-Tryptophane Methyl Ester (Compound F English Name: (R)-methyl-2-amino-3-(1H-indol-3-yl) propanoate) In a three-neck flask equipped with mechanical stirring, add 600 mL of anhydrous methanol, D-tryptophan (102.1 g, 500 mmol), stir at room temperature, and use an ice salt bath to reduce the temperature of the reaction system to 0°C. Thionyl chloride (71.4 g, 600 mmol) was added, and the mixture was warmed to room temperature for about 12 hours after the dropwise addition. TLC monitoring, when the reaction of the raw materials is complete, the reaction is stopped. After evaporating most of the remaining thionyl chloride and methanol at atmospheric pressure, thionyl chloride and methanol are removed under reduced pressure, and cooled to obtain the hydrochloride salt of solid tryptophan methyl ester (air-insulated, low temperature can be stored for a long time). . When free tryptophan methyl ester is to be used, a small amount of the hydrochloride of tryptophan methyl ester is taken and dissolved in chloroform. The solution is washed with a saturated solution of sodium bicarbonate to weak alkalinity, and the organic layer is dried to remove the solvent chloroform. The resulting solid (ie, tryptophan methyl ester) is vacuum dried and, in general, can be used directly in the next step asymmetric catalytic reaction without further purification. If it is really needed, the tryptophan methyl ester can be recrystallized using a mixed solvent of toluene and n-hexane, and the resulting recrystallized solid can be used in the next step asymmetric catalytic reaction after vacuum drying.
	Stage #1: methanol; D-tryptophan With thionyl chloride at 0℃; Reflux; Stage #2: With sodium methylate In methanol for 0.0125h;
	Stage #1: methanol; D-tryptophan With chloro-trimethyl-silane at 20℃; Stage #2: With triethylamine In methanol; diethyl ether at -10℃; for 1h;	Typical procedure for amino alcohols from amino acids (compounds 1a-e) General procedure: To a flask containing DL-1-Naphthylalanine (1a) (1.0 g, 4.6 mmol), TMSCl (1.51 g, 14 mmol, 3 eq) was added, followed by anhydrous methanol (10 mL). The reaction was allowed to stir at room temperature overnight. Upon completion, the volatiles were removed in vacuo, affording the crude methyl ester hydrochloride (1.34 g). The crude salt was then dissolved in ethyl ether:methanol (7.5:1; 30 mL:4 mL) and cooled to -10 °C. Triethylamine (6 mL) was slowly added and the reaction was stirred for one hour at -10 °C. After reaction completion, the solution was filtered through a pad of celite to remove Et3N salt, and the filtrate was evaporated in vacuo affording the free base methyl ester (1.14 g). The methyl ester was dissolved in methanol (35 mL) and placed on an ice bath. Sodium borohydride (10 eq) was added portion-wise over 20 min and the reaction was allowed to come to room temperature overnight. The solvent was then evaporated, diluted with H2O (80 mL), and extracted with EtOAc (3 × 100 mL). The combined organic layers were dried over MgSO4, filtrated and concentrated in vacuo affording 2a as a white powder (0.87 g, 94%), which was used without further purification. 1H NMR (400 MHz, CDCl3T) δ8.05 (d, J = 7.0 Hz, 1H), 7.88 (d, J = 9.1 Hz, 1H), 7.77 (d, J = 8.7 Hz,1H), 7.53 (sext, J = 7.6 Hz, 2H), 7.43 (t, J = 7.7 Hz, 1H), 7.36 (d,J = 6.2 Hz, 1H), 3.72 (dd, J = 3.7, 10.6 Hz, 1H), 3.49 (dd, J = 6.6,10.6 Hz, 1H), 3.33 (m, 2H), 2.95 (dd, J = 9.7, 14.8 Hz, 1H). HRMS m/zcalculated for C13H16NO [M+H]+: 202.1232. Found: 202.1227.
	Stage #1: methanol; D-tryptophan at 0℃; for 0.0833333h; Stage #2: With acetyl chloride at 0℃; for 5h; Reflux; Stage #3: With ammonium hydroxide	4.1.1. General synthetic methods and experimental details General procedure: 4.1.1.1. Procedure A, synthesis of D- & L-tryptophan methyl ester. A250 mL round bottom flask containing methanol (140 mL), wascooled to 0 °C, then solid D or L-Tryptophan (20 g, 97.93 mmol) wasadded in one portion. The solution was stirred for 5 min, then acetylchloride (25 mL) was added dropwise using a dropping funnel over aperiod of 15 min, the solution was then heated to reflux for 5 h. Then itwas allowed to cool to room temperature and the solvent was removedunder reduced pressure to give tryptophan methyl ester hydrochloride.The free base was obtained by adding 50 mL dilute NH4OH andextraction with CH2Cl2 (3 × 50 mL). The combined organic extractswere dried over anhydrous MgSO4, evaporated under reduced pressureto give the D- or L-tryptophan methyl ester, that was used in the nextstep without further purification [40,42].
	With thionyl chloride at 0 - 25℃; for 21h; Inert atmosphere;

Reference： [1]Current Patent Assignee: SHANDONG ACAD PHARMACEUTICAL SCIENCES; SHANDONG HAIYOU FREDA PHARMACY - CN110437228, 2019, A Location in patent: Paragraph 0026-0034
[2]Devi, Parthiban Brindha; Jogula, Sridhar; Reddy, Asireddy Parameshwar; Saxena, Shalini; Sridevi, Jonnalagadda Padma; Sriram, Dharmarajan; Yogeeswari, Perumal [Molecular Informatics, 2015, vol. 34, # 2-3, p. 147 - 159]
[3]Current Patent Assignee: SUZHOU HOMESUN PHARMACEUTICAL - CN111253399, 2020, A Location in patent: Paragraph 0014-0015
[4]Robaa, Dina; Enzensperger, Christoph; Eldin Abulazm, Shams; Hefnawy, Mohamed M.; El-Subbagh, Hussein I.; Wani, Tanveer A.; Lehmann, Jochen [Journal of Medicinal Chemistry, 2011, vol. 54, # 20, p. 7422 - 7426]
[5]Location in patent: scheme or table Smil, David V.; Manku, Sukhdev; Chantigny, Yves A.; Leit, Silvana; Wahhab, Amal; Yan, Theresa P.; Fournel, Marielle; Maroun, Christiane; Li, Zuomei; Lemieux, Anne-Marie; Nicolescu, Alina; Rahil, Jubrail; Lefebvre, Sylvain; Panetta, Anthony; Besterman, Jeffrey M.; Déziel, Robert [Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 3, p. 688 - 692]
[6]Jiang, Chun-Xiao; Yu, Bo; Miao, Ya-Mei; Ren, Hao; Xu, Qianhe; Zhao, Chun; Tian, Li-Li; Yu, Zhen-Qing; Zhou, Pan-Pan; Wang, Xiaolei; Fang, Jianguo; Zhang, Jiwen; Zhang, Jin Z.; Wu, Quan-Xiang [Journal of Natural Products, 2021, vol. 84, # 9, p. 2468 - 2474]
[7]Zapf, Christoph W.; Del Valle, Juan R.; Goodman, Murray [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 18, p. 4033 - 4036]
[8]Song, Hao; Yang, Jun; Chen, Wei; Qin, Yong [Organic Letters, 2006, vol. 8, # 26, p. 6011 - 6014]
[9]Current Patent Assignee: 4 SC AG - WO2006/79645, 2006, A1 Location in patent: Page/Page column 34
[10]Location in patent: scheme or table Gupta, Leena; Srivastava, Kumkum; Singh, Shubhra; Puri; Chauhan, Prem M.S. [Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 11, p. 3306 - 3309]
[11]Location in patent: body text Cardoso, Ana Lúcia; Lopes, Susana M.M.; Matos Beja, Ana; Ramos Silva, Manuela; de los Santos, Jesús M.; Pinho e Melo, Teresa M.V.D.; Palacios, Francisco [Tetrahedron, 2009, vol. 65, # 45, p. 9116 - 9124]
[12]Location in patent: scheme or table Abadi, Ashraf H.; Gary, Bernard D.; Tinsley, Heather N.; Piazza, Gary A.; Abdel-Halim, Mohammad [European Journal of Medicinal Chemistry, 2010, vol. 45, # 4, p. 1278 - 1286]
[13]Location in patent: experimental part Kumar, Ravi; Gupta, Leena; Pal, Pooja; Khan, Shahnawaz; Singh, Neetu; Katiyar, Sanjay Babu; Meena, Sanjeev; Sarkar, Jayanta; Sinha, Sudhir; Kanaujiya, Jitendra Kumar; Lochab, Savita; Trivedi, Arun Kumar; Chauhan, Prem M.S. [European Journal of Medicinal Chemistry, 2010, vol. 45, # 6, p. 2265 - 2276]
[14]Location in patent: scheme or table Chauhan, Shikha S.; Gupta, Leena; Mittal, Monika; Vishwakarma, Preeti; Gupta, Suman; Chauhan, Prem M.S. [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 21, p. 6191 - 6194]
[15]Location in patent: experimental part Mohamed, Heba A.; Girgis, Nancy M. R.; Wilcken, Rainer; Bauer, Matthias R.; Tinsley, Heather N.; Gary, Bernard D.; Piazza, Gary A.; Boeckler, Frank M.; Abadi, Ashraf H. [Journal of Medicinal Chemistry, 2011, vol. 54, # 2, p. 495 - 509]
[16]Location in patent: scheme or table Ahmed, Nermin S.; Gary, Bernard D.; Tinsley, Hethar N.; Piazza, Gary A.; Laufer, Stefan; Abadi, Ashraf H. [Archiv der Pharmazie, 2011, vol. 344, # 3, p. 149 - 157]
[17]Location in patent: scheme or table Ahmed, Nermin S.; Gary, Bernard D.; Piazza, Gary A.; Tinsley, Heather N.; Laufer, Stefan; Abadi, Ashraf H. [Medicinal Chemistry, 2010, vol. 6, # 6, p. 374 - 387]
[18]Location in patent: scheme or table Wang, Mingzhong; Feng, Xiangyang; Cai, Liangzhen; Xu, Zhengshuang; Ye, Tao [Chemical Communications, 2012, vol. 48, # 36, p. 4344 - 4346]
[19]Ahmed, Nermin S.; Ali, Amal H.; El-Nashar, Shreen M.; Gary, Bernard D.; Fajardo, Alexandra M.; Tinsley, Heather N.; Piazza, Gary A.; Negri, Matthias; Abadi, Ashraf H. [European Journal of Medicinal Chemistry, 2012, vol. 57, p. 329 - 343]
[20]El-Gamil, Dalia S.; Ahmed, Nermin S.; Gary, Bernard D.; Piazza, Gary A.; Engel, Matthias; Hartmann, Rolf W.; Abadi, Ashraf H. [Archiv der Pharmazie, 2013, vol. 346, # 1, p. 23 - 33]
[21]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]
[22]Current Patent Assignee: TEL AVIV UNIVERSITY - US9096645, 2015, B2 Location in patent: Page/Page column 21; 22
[23]Shankaraiah, Nagula; Sharma, Pankaj; Pedapati, Srinivas; Nekkanti, Shalini; Srinivasulu, Vunnam; Kumar, Niggula Praveen; Kamal, Ahmed [Letters in drug design and discovery, 2016, vol. 13, # 4, p. 335 - 342]
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[26]Current Patent Assignee: XIHUA UNIVERSITY - CN107556308, 2018, A Location in patent: Paragraph 0020
[27]Current Patent Assignee: XIHUA UNIVERSITY - CN107417685, 2017, A Location in patent: Paragraph 0025
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21
[ 153-94-6 ]
[ 348080-83-1 ]
[ 348081-12-9 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; N,O-Bis(trimethylsilyl)trifluoroacetamide In N,N-dimethyl-formamide at 0 - 60℃; for 2.5h;	31.1 (R)-Tryptophan (0.3 g) was taken up in DMF (1 ml) and pyridine (1 ml) and treated with BSTFA (0.85 ml). The mixture was warmed to 60[deg.] C. After 30 min at 60[deg.] C. the solution was cooled to 0[deg.] C. and a solution of benzo[b]thiophene-5-methanesulfonyl chloride (0.3 g) in DMF (1 ml) was added dropwise. The reaction mixture was left stirring at rt for 2 h and then treated with methanol (1 ml). The solution was then passed through a Bond Elut PSA column. After initial elution with methanol (30 ml) the product was eluted with 4% TFA in THF (20ml). The THF solution was stripped to dryness and triturated with hexane to give the subtitle compound (0.3 g).

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - US2003/199571, 2003, A1 Location in patent: Page/Page column 12

22
[ 76-83-5 ]
[ 153-94-6 ]
(R)-3-(1H-indol-3-yl)-2-(N-triphenylmethylamino)propanoic acid [N-trityltryptophan] [ No CAS ]
[ 108826-79-5 ]

Yield	Reaction Conditions	Operation in experiment
79%	With chloro-trimethyl-silane; triethylamine; citric acid In diethyl ether; dichloromethane	a (a) (a) Preparation of (R)-3-(1H-indol-3-yl)-2-(N-triphenylmethylamino)propanoic acid [N-trityltryptophan] STR13 Chlorotrimethylsilane (70.0 ml, 0.527 mol) was added at a moderate rate to a stirred slurry of D-tryptophan (100.0 g, 0.490 mol) in anhydrous methylene chloride (800 ml) under a nitrogen atmosphere. This mixture was continuously stirred for 4.25 hours. Triethylamine (147.0 ml, 1.055 mol) was added, followed by the addition of a solution of triphenylmethyl chloride (147.0 g, 0.552 mol) in methylene chloride (400 ml) using an addition funnel. The mixture was stirred at room temperature, under a nitrogen atmosphere for at least 20 hours. The reaction was quenched by the addition of methanol (500 ml). The solution was concentrated on a rotary evaporator to near dryness and the mixture was redissolved in methylene chloride and ethyl acetate. An aqueous work-up involving a 5% citric acid solution (2) and brine (2) was then performed. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to dryness on a rotary evaporator. The solid was dissolved in hot diethyl ether followed by the addition of hexanes to promote crystallization. By this process 173.6 g (0.389 mol) of analytically pure (R)-3-(1H-indol-3-yl)-2-(N-triphenylmethylamino)propanoic acid was isolated as a white solid in two crops giving a total of 79% yield. FDMS 446 (M+). 1 H NMR (DMSO-d6) δ 2.70 (m, 1H), 2.83 (m, 2H), 3.35 (m, 1H), 6.92-7.20 (m, 12H), 7.30-7.41 (m, 8H), 10.83 (s, 1H), 11.73 (br s, 1H). Analysis for C30 H26 N2 O2: Theory: C, 80.69; H, 5.87; N, 6.27. Found: C, 80.47; H, 5.92; N, 6.10.

Reference： [1]Current Patent Assignee: ELI LILLY & CO - US5846973, 1998, A

23
(R)-tryptophan sodium salt [ No CAS ]
[ 153-94-6 ]
[ 191279-37-5 ]
[ 66863-43-2 ]

Yield	Reaction Conditions	Operation in experiment
1: 81% 2: 84%	With sodium hydroxide; formaldehyd In water	4 H--tpi--Phe--trp--Leu--Met--NH2 EXAMPLE 4 H--tpi--Phe--trp--Leu--Met--NH2 H--tpi--OH was prepared by the method of Lippke et al. (J. Med. Chem., vol. 26, pp. 500-503, 1983) from D-tryptophan sodium salt (prepared from 20 g. of D-tryptophan and 3.9 g. of sodium hydroxide) and aqueous formaldehyde (37%, 15.9 g.) in water (50 ml.). The product was obtained by crystallization in two crops (12.77 g., m.r. 290°-292° C.; 4.31 g., m.r. 292°-295° C.; 81% yield). Boc--tpi--OH was prepared from H--tpi--OH (2.9 g.) and di-t-butyl dicarbonate (3.7 g.) in dioxane (30 ml.)-water (30 ml.) containing triethylamine (2.8 ml.) at room temperature. The crude product was crystallized from methanol in three crops (0.36 g., m.p. 320° C. with decomposition; 1.05 g.; 0.69 g.; 84% yield).

Reference： [1]Current Patent Assignee: BAYER AG - US4839465, 1989, A

24
[ 7732-18-5 ]
[ 76-83-5 ]
[ 153-94-6 ]
[ 108826-79-5 ]

Yield	Reaction Conditions	Operation in experiment
79%	With chloro-trimethyl-silane; triethylamine; citric acid In diethyl ether; dichloromethane	Tritylation Tritylation Chlorotrimethylsilane (70.0 ml, 0.527 mol) was added at a moderate rate to a stirred slurry of D-tryptophan (100.0 g, 0.490 mol) in anhydrous methylene chloride (800 ml) under a nitrogen atmosphere. This mixture was continuously stirred for 4.25 hours. Triethylamine (147.0 ml, 1.055 mol) was added, followed by the addition of a solution of triphenylmethyl chloride (147.0 g, 0.552 mol) in methylene chloride (400 ml) using an addition funnel. The mixture was stirred at room temperature, under a nitrogen atmosphere for at least 20 hours. The reaction was quenched by the addition of methanol (500 ml). The solution was concentrated on a rotary evaporator to near dryness and the mixture was redissolved in methylene chloride and ethyl acetate. An aqueous work-up involving a 5% citric acid solution (2X) and brine (2X) was then performed. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to dryness on a rotary evaporator. The solid was dissolved in hot diethyl ether followed by the addition of hexanes to promote crystallization. By this process 173.6 g (0.389 mol) of analytically pure (R)-3-(1H-indol-3-yl)-2-(N-triphenylmethylamino)propanoic acid was isolated as a white solid in two crops giving a total of 79% yield. FDMS 446 (M+). 1H NMR (DMSO-d6) δ 2.70 (m, 1H), 2.83 (m, 2H), 3.35 (m, 1H), 6.92-7.20 (m. 12H) 7.30-7.41 (m, 8H), 10.83 (s, 1H), 11.73 (br s, 1H).
79%	With chloro-trimethyl-silane; triethylamine; citric acid In diethyl ether; dichloromethane	Tritylation Tritylation Chlorotrimethylsilane (70.0 ml, 0.527 mol) was added at a moderate rate to a stirred slurry of D-tryptophan (100.0 g, 0.490 mol) in anhydrous methylene chloride (800 ml) under a nitrogen atmosphere. This mixture was continuously stirred for 4.25 hours. Triethylamine (147.0 ml, 1.055 mol) was added, followed by the addition of a solution of triphenylmethyl chloride (147.0 g, 0.552 mol) in methylene chloride (400 ml) using an addition funnel. The mixture was stirred at room temperature, under a nitrogen atmosphere for at least 20 hours. The reaction was quenched by the addition of methanol (500 ml). The solution was concentrated on a rotary evaporator to near dryness and the mixture was redissolved in methylene chloride and ethyl acetate. An aqueous work-up involving a 5% citric acid solution (2X) and brine (2X) was then performed. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to dryness on a rotary evaporator. The solid was dissolved in hot diethyl ether followed by the addition of hexanes to promote crystallization. By this process 173.6 g (0.389 mol) of analytically pure (R)-3-(1H-indol-3-yl)-2-(N-triphenylmethylamino)propanoic acid was isolated as a white solid in two crops giving a total of 79% yield. FDMS 446 (M+). 1H NMR (DMSO-d6) δ 2.70 (m, 1H), 2.83 (m, 2H), 3.35 (m, 1H), 6.92-7.20 (m, 12H), 7.30-7.41 (m, 8H), 10.83 (s, 1H), 11.73 (br s, 1H).

Reference： [1]Current Patent Assignee: ELI LILLY & CO - EP747049, 1996, A1
[2]Current Patent Assignee: ELI LILLY & CO - EP747055, 1996, A2

25
[ 86-90-8 ]
[ 153-94-6 ]
(R)-2-(5-bromo-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(1H-indol-3-yl)-propionic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide; at 100℃; for 7h;	A mixture of the relevant substituted phthalic anhydrides (25 mmol), L-tryptophan (25 mmol) and DMF (70 mL) was heated at 100 0C for seven hours. The crude reaction mixture was diluted with ethyl acetate (250ml) and washed with brine (3 x 120ml). The organic layer was dried (MgSO4), filtered and the solvent removed in vacuo. The crude material was purified by chromatography column (DCM:MeOH:AcOH (95:4:1) elution) to give the pure product. Method: LCMS1. EPO <DP n="42"/>The compounds made are listed below:

Reference： [1]Patent: WO2007/7054,2007,A1 .Location in patent: Page/Page column 40-41

26
[ 98-59-9 ]
[ 153-94-6 ]
[ 136891-53-7 ]

Yield	Reaction Conditions	Operation in experiment
86%	With triethylamine In tetrahydrofuran; water at 0 - 20℃; for 2.5h; Inert atmosphere;
83%	With triethylamine In tetrahydrofuran; water at 0 - 20℃; Inert atmosphere;

Reference： [1]Qi, Na; Allu, Srinivasa Rao; Wang, Zhanlong; Liu, Qiang; Guo, Jian; He, Yun [Organic Letters, 2016, vol. 18, # 18, p. 4718 - 4721]
[2]Schindler, Corinna S.; Stephenson, Corey R. J.; Carreira, Erick M. [Angewandte Chemie - International Edition, 2008, vol. 47, # 46, p. 8852 - 8855]

27
[ 55854-46-1 ]
[ 153-94-6 ]
[ 203640-36-2 ]

Yield	Reaction Conditions	Operation in experiment
71%	With triethylamine; In 1,4-dioxane; water; at 20℃;	General procedure: 5-Bromothiophene-2-sulfonylchloride (1g, 4.43 mmol) was added to a solution of the appropriate non-natural commercial amino acid (4.43 mmol) in H2O (4.43 mL) and dioxane (13.3 mL) containing Et3N (1.24 mL, 8.86 mmol). The mixture was stirred at room temperature overnight, the dioxane was evaporated and the residue was treated with EtOAc and washed with HCl 1 N and brine. Organic layers were then collected, dried over Na2SO4, and evaporated in vacuo.
		To a suspension of (R)-2-Amino-3-(lH-indol-3-yl)-propionic acid 2 (0.23 g, 1.12 mmol) (Alfa-Aesar, A- 18426) in acetone (3 mL) was added 2M sodium carbonate (1 mL) to stir at room temperature for 30 minutes. To this mixture was added bromosulfonyl chloride 1 (0.13g, 0.5 mmol) (Alfa-Aesar, A-14677) at 0 0C to stir for 15 minutes. The reaction mixture was stirred further for 1 hour at room temperature. After pouring into water (20 mL), the solution was washed with ether (x3). The aqueous layer was acidified with IM HCl, followed by extraction with ethyl acetate (x3). The combined organic extracts were then washed with brine and dried (Na2SC^) to provide the crude (R)-2-(5-Bromo- thiophene-2-sulfonylamino)-3-(lH-indol-3-yl)-propionic acid product (3) (O.lg, 74 %). LC-MS (ES+) 429, 431; (ES-) 427, 429.A portion of the crude (R)- 2-(5-Bromo-thiophene-2-sulfonylamino)-3-(lH-indol-3-yl)- propionic acid product (3) was taken to the next step without further purification.
		Example 1; Step A; To a suspension of (R)-2-Amino-3-(1H-indol-3-yl)-propionic acid 2 (0.23 g , 1.12 mmol ) (Alfa-Aesar, A-18426) in acetone (3 mL ) was added 2M sodium carbonate (1 mL ) to stir at room temperature for 30 minutes . To this mixture was added bromosulfonyl chloride 1 (0.13 g , 0.5 mmol ) (Alfa-Aesar, A-14677) at 0 C. to stir for 15 minutes . The reaction mixture was stirred further for 1 hour at room temperature . After pouring into water (20 mL ), the solution was washed with ether (×3). The aqueous layer was acidified with 1M HCl , followed by extraction with ethyl acetate (×3). The combined organic extracts were then washed with brine and dried (Na2SO4 ) to provide the crude (R)-2-(5-Bromo-thiophene-2-sulfonylamino)-3-(1H-indol-3-yl)-propionic acid product (3) (0.16 g , 74% ). LC- MS (ES+) 429, 431 ; (ES-) 427, 429.A portion of the crude (R)-2-(5-Bromo-thiophene-2-sulfonylamino)-3-(1H-indol-3-yl)-propionic acid product (3) was taken to the next step without further purification.

Example 11 2 3Step ATo a suspension of (R)-2-Amino-3-(lH-indol-3-yl)-propionic acid 2 (0.23 g, 1.12 mmol) (Alfa-Aesar, A- 18426) in acetone (3 mL) was added 2M sodium carbonate (1 mL) to stir at room temperature for 30 minutes. To this mixture was added bromosulfonyl chloride 1 (0.13g, 0.5 mmol) (Alfa-Aesar, A-14677) at 0 C to stir for 15 minutes. The reaction mixture was stirred further for 1 hour at room temperature. After pouring into water (20 mL), the solution was washed with ether (x3). The aqueous layer was acidified with 1M HC1, followed by extraction with ethyl acetate (x3). The combined organic extracts were then washed with brine and dried (Na2S04) to provide the crude (R)-2-(5-Bromo- thiophene-2-sulfonylamino)-3-(lH-indol-3-yl)-propionic acid product (3) (0.16g, 74 %). LC-MS (ES+) 429, 431 ; (ES-) 427, 429.A portion of the crude (R)- 2-(5-Bromo-thiophene-2-sulfonylamino)-3-(lH-indol-3-yl)- propionic acid product (3) was taken to the next step without further purification.

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 2617 - 2629
[2]Patent: WO2010/75287,2010,A2 .Location in patent: Page/Page column 44
[3]Patent: US2011/230452,2011,A1 .Location in patent: Page/Page column 13-14
[4]Patent: WO2012/118498,2012,A1 .Location in patent: Page/Page column 32-33

28
[ 292638-85-8 ]
[ 153-94-6 ]
[ 1259372-31-0 ]

Yield	Reaction Conditions	Operation in experiment
85%	With triethylamine In methanol; water at 20℃;

Reference： [1]Chen, Pinhong; Cao, Lidong; Tian, Wenhai; Wang, Xinfeng; Li, Chaozhong [Chemical Communications, 2010, vol. 46, # 44, p. 8436 - 8438]

29
[ 34404-30-3 ]
[ 153-94-6 ]
[ 1401719-78-5 ]

Yield	Reaction Conditions	Operation in experiment
79%		Example 6 Preparation of H-D-Glu( -Trp-OH)-0-Bzl, Apo829 A. Preparation of Boc-D-Glu(D-Trp-OH)-0-Bzl Boc-D-Glu-OBz. ( 1.24 g, 33.3 mmol) was mixed with HOSu (3.83 g, 33.3 mrnol) and EDCI hydrochloride (6.38 g, 33.3 mmol) in DMF (80 mL) at room temperature and stirred for overnight. D-Trp-OH (10.2 g; 50 mmol) was added all at once and the reaction mixture was stirred at room temperature for another 6 h. The mixture was then quenched with a 0.5N HCI solution (250 mL) as a sticky solid formed. The liquid fraction was decanted and the residual sticky solid was dissolved in ethyl acetate (200 mL). The ethyl acetate layer was washed with a 0.5 N HCI solution (100 mL x 2), water (100 mL x 2) and brine, dried over MgS04 and filtered. The filtrate was concentrated in vacuo by rotary evaporation and the residue was triturated with ether to give Boc-D-Glu(D-Trp-OH)-0-Bzl as a white solid (6.60 g). The mother liquid was concentrated and triturated with 10 % ethyl acetate in hexanes to give a second crop of product as off-white solid (7.23 g). Combined yield = 13.82g (79%); 1H NMR (DMSO-DB, 400MHz) S (ppm): 10.82 (br. s, 1H), 8.09 (d, J = 7.1 Hz, 1H), 7.51 (d, J = 7.1 Hz, 1H), 7.27 - 7.41 (m, 7H), 7.11 (s, 1 H), 7.05 (t, J = 7.1 Hz: 1 H), 6.92 - 7.00 (m, 1 H), 5.01 - 5.21 (m, 2H), 4.39 - 4.51 (m, 1 H), 3.94 - 4.06 (m, 1 H), 3.08 - 3.19 (m, 1 H), 2.93 - 3.06 (m, 1 H), 2.05 - 2.26 (m, 2H), 1.82 - 1.98 (m, 1 H), 1 .67 - 1 .79 (m, 1 H), 1.37 (s, 9H); MS (m/z) 524 [M+1]+.

Reference： [1]Patent: WO2012/129671,2012,A1 .Location in patent: Page/Page column 38-39

30
[ 65706-99-2 ]
[ 153-94-6 ]
[ 1382326-04-6 ]

Yield	Reaction Conditions	Operation in experiment
88%		Example 7 Preparation of H-D-Glu(D-Trp-0-CH(CH3)-0-CO-0-cyclohexyl)-OH (Apo843). A. Preparation of Cbz-D-Glu(D-Trp-OH)-0-Bzl. Cbz-D-Glu(OH)-0-Bzl (18.57 g, 50 mmol), HOSu (5.76 g, 50 mmol) andEDCI.HCI (9.59 g, 50 mmol) were mixed in DMF (100 mL) at ice-water bath temperature. The reaction mixture was allowed to warm to RT then stirred at RT for overnight. The reaction mixture was cooled again in an ice-water bath and D-Trp-OH (10.21 g, 50 mmol) was added. The mixture was then stirred at RT for 6 h. The mixture was poured into a beaker containing a mixture of 0.5N HCI (200 mL) and ice chunks. The mixture was extracted with ethyl acetate twice (200 mL ? 100 mL). The organic layers were combined and washed with water (100 mL x3) and brine (100 mL), dried over magnesium sulphate and filtered. The filtrate was concentrated by rotary evaporation under reduced pressure and the resulting solid was triturated with a mixture of ether and hexanes. Cbz-D-Glu(D- Trp-OH)-0-Bzl (24.5 g) was obtained as a white solid after suction filtration. Yield = 88%; 1H NMR (DMSO-D6, 400 MHz) delta ppm: 12.55 (br. s, 1H), 10.81 (s, 1H), 8.11 (d, J = 8.1 Hz, 1H), 7.78 (d, J = 8.1 Hz, 1H), 7.51 (d, J = 7.1 Hz, 1H), 7.19 -7.45 (m, 11 H), 7.11 (s, 1 H), 7.05 (t, J = 7.6 Hz, 1H), 6.96 (t, J = 7.6 Hz, 1H), 4.92 - 5.22 (m, 4H), 4.37 -4.55 (m, 1 H), 3.99 -4.17 (m, 1 H), 3.14 (dd, J =,14.7, 5.6 Hz, 1H). 2.92 - 3.07 (m, 1 H), 2.08 - 2.33 (m, 2H), 1.85 - 2.07 (m, 1H), 1.64 - 1.85 (m, 1 H); MS-ESI (m/z): 558 [M-M]*.

Reference： [1]Patent: WO2012/129671,2012,A1 .Location in patent: Page/Page column 40-41

31
[ 97996-97-9 ]
[ 153-94-6 ]
[ 1382326-14-8 ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: α-ethyl D-N-carbobenzoxyglutamate With 1-hydroxy-pyrrolidine-2,5-dione; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; Cooling with ice-water; Stage #2: D-tryptophan In N,N-dimethyl-formamide at 20℃; Cooling with ice-water; Stage #3: With hydrogenchloride In water; N,N-dimethyl-formamide Cooling with ice;	19 Example 19 Preparation of H-D-Glu(D-Trp-0-CH(CH3)0-CO-0-cyclohexyl)-0-Et hydrochloride salt, Apo854.HCI Cbz-D-Glu(OH)-0-Et (12.1 g, 39.1 mmol), HOSu (4.60 g, 40.0 mmol) andEDCI.HCI (7.67 g, 40.0 mmol) were mixed in DMF (100 mL) under ice-water bath temperature. The reaction mixture was allowed to warm to RT then stirred for overnight. The reaction mixture was cooled again in an ice-water bath and D-Trp- OH (8.17 g, 40.0 mmol) was added. The mixture was stirred at room temperature for overnight. The mixture was poured into a beaker containing 0.5N HCI (200 mL) and ice pellets. The mixture was extracted with ethyl acetate (2x200 mL + 1x100 mL). The organic layers were combined and washed with a 0.5N HCI solution (100 mL), water (2x100 mL) and brine (100 mL), dried over MgS04, then filtered. The filtrate was concentrated via rotary evaporation under reduced pressure and the resulting solid Cbz-D-Glu(D-Trp-OH)-0-Et was triturated with10% ethyl acetate in hexanes. The precipitated white solid was collected via suction filtration (17.6 g). Yield = 90 %; 1H NMR (DMSO-D6l 400 MHz) δ ppm: 12.58 (br. s, 1 H), 10.82 (s, 1H), 8.12 (d, J = 8.1 Hz, 1 H), 7.71 (d, J = 8.1 Hz, 1 H), 7.52 (d, J = 8.1 Hz, 1H), 7.23 - 7.42 (m, 6H), 7.12 (s, 1 H), 7.06 (t, J = 7.6 Hz, 1 H), 6.97 (t, J = 7.6 Hz, 1H), 4.97 - 5.10 (m, 2H), 4.41 - 4.51 (m, 1H), 3.95 - 4.15(m, 3H), 3.15 (dd, J = 14.1 , 5.1 Hz, 1H), 2.99 (dd, J = 15.2, 8.1 Hz, 1 H), 2.09 - 2.26 (m, 2H), 1.83 - 1.96 (m. 1 H), 1.65 - 1.81 (m, 1 H), 1.16 (t, J - 7.1 Hz, 3H); MS-ESI (m/z): 496 [ +1f. To a mixture of Cbz-D-Glu(D-Trp-OH)-0-Et {4.95 g, 0.0 mmol) with potassium carbonate (4.15 g, 30.0 mmol) and sodium iodide (6.00 g, 40.0 mmol) in Λ/,/V-dimethylformamide (30 mL) at room temperature, 1-chtoroethylcyclohexyl carbonate (6.20 g, 30.0 mmol) was added. After being stirred at room temperature for overnight, additional W,/V-dimethylformamide (30 mL) was added and the reaction mixture was stirred at 40°C for overnight. The reaction mixture was diluted with ethyl acetate then washed with water (3x) then with brine. The crude product Cbz-D-Glu(D-Trp-0-CH(CH3)-0-CO-0-cyclohexyl)-0-Et was purified by column chromatography on silica gel using a solvent gradient of a mixture of ethyl acetate in hexanes (20 to 40%) as eluant. Fractions rich in product were combined together and evaporated to dryness. Thus, the desired compound Cbz-D-Glu(D-Trp-0-CH(CH3)-0-CO-0-cyclohexyl)-0-Et (4.43 g) was obtained as a pale-yellow foam. Yield = 66 %; 1H NMR (DMSO-D6> 400 MHz) δ ppm: 10.86 (or. s, 1H), 8.36 (dd, J = 17.2, 7.1 Hz, 1 H), 7.66 - 7.77 (m, 1 H), 7.46(t, J = 8.0 Hz., 1H), 7.22 - 7.42 (m, 6H), 7.10 - 7.20 (m, 1 H), 7.02 - 7.10 (m, 1 H), 6.90 - 7.02 (m, 1 H), 6.58 - 6.70 (m, 0.5H), 6.46 - 6.58 (m, 0.5H), 5.04 (br. s, 2H), 4.38 - 4.61 (m, 2H), 3.93 - 4.15 (m, 3H), 2.90 - 3.17 (m, 2H), 2.20 (br. s, 2H), 1.54 - 1.96 (m, 6H), 1.02 - 1.53 (m, 12H); MS-ESI (m/z): 666 [M+1f. Cbz-D-Glu(D-Trp-0-CH(CH3)-0-CO-0-cyclohexyl)-0-Et (2.0 g, 3.0 mmol) and 10 % Pd/C (wet, 0.6 g) was mixed in ethanol (50 mL) and 2 HCI in ether (1.7 mL, 3.4 mmol). The reaction mixture was hydrogenated in a Parr apparatus at 20-25 psi of hydrogen pressure for an hour. The mixture was filtered through Celite and the cake was washed with ethanol. The filtrate was concentrated by rotary evaporation and the residue was triturated with a mixture of ether and hexanes. Thus, H-D-Glu(D-Trp-O-CH(CH3)-0-CO-0-cyclohexyl)-0-Ethydrochloride salt (Apo854.HCI, 0.80 g) was obtained as a pink solid foam. Yield = 47%; *H NMR (DMSO-D6, 400 MHz) δ ppm: 0.94 (br. s, 1 H), 8.57 (br. s, 4H), 7.47 (t, J = 8.1 Hz, 1H), 7.34 (d, J = 8.1 Hz, 1H), 7.19 (s, 1 H), 7.07 (t, J = 7.6 Hz, 1 H), 6.88 - 7.03 (m, 1 H), 6.58 - 6.72 (q, J = 5.1 Hz, 0.5H), 6.53 (q, J = 5.1 Hz,0.5H), 4.39 - 4.63 (m, 2H), 4.00 - 4.26 (m, 2H), 3.78 - 4.00 (m, 1 H), 2.93 - 3.18 (m, 2H), 2.18 - 2.41 (m, 2H), 1.88 - 2.02 (m, 2H), 1.82 (br. s, 2H), 1.63 (br. s, 2H), 1.13 - 1.53 (m, 12H); MS-ESI (m/z): 532 [M+1]+ (free base).

Reference： [1]Current Patent Assignee: APOTEX INC - WO2012/129671, 2012, A1 Location in patent: Page/Page column 53-54

32
[ 67-56-1 ]
[ 153-94-6 ]
(R)-methyl 2-amino-3-(1H-indol-3-yl)propanoate hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With thionyl chloride In methanol for 24h; Reflux;	2a Synthesis Example 2a - (2f?)-3-(1H-indol-3-vl)-1-methoxy-1-oxopropan-2-aminium chlorideThionyl chloride (9.87 mmol, 0.72 mL) was added dropwise to a solution of D- tryptophan (1.000 g, 4.89 mmol) in methanol (33 mL). The reaction was heated to reflux with vigorous stirring for 24 h. After cooling, the reaction mixture was concentrated under reduced pressure and residual methanol traces removed by azeotropic distillation with dichloromethane (10 mL) under reduced pressure to give the title compound as a white solid (1.070 g, 86%).1H MR (500 MHz, D20) δ = 7.52 (1 H, d, 7=7.9, 9-H), 7.46 (1 H, d, 7=8.1 , 12-H), 7.26 - 7.10 (3H, m, 4, 5, 9-H), 4.37 (1H, t, J=6.0, 2-H), 3.73 (3H, s, 3-H), 3.44 - 3.31 (2H, m, 4-H).13C NMR (126 MHz, D20) δ = 170.4 (2-C), 136.3 (7-C), 126.4 (8-C), 25.4 (6-C),122.3 (11-CH), 119.6 (10-CH), 118.1 (9-CH), 112.1 (12-CH), 106.0 (5-C), 53.6 (13- CH3), 53.3 (2-CH), 25.7 (4-CH2).IR (diamond, vMAX> cm"1) 3261 (NH st), 2870 (Nf-H st), 2023 (Ar comb), 1748 (C=0 St), 1229, 1211 (CO-0 st as), 1181 (C-0 st as).Acc. Mass (FAB): Ci2H15 202 Found: 219.1120 m/z Calculated: 219.1128 m/z
	With thionyl chloride at 0 - 20℃; for 12h;	5 Example 5: Synthesis of tryptophan methyl ester (Compound F English name: (R) -methyl 2-amino-3- (1H-Indol-3-yl) propanoate hydrochloride In a three-necked flask equipped with a mechanical stirrer,Add anhydrous methanol 600 mL,D-tryptophan (102.1 g, 500 mmol), Room temperature stirring, using ice salt bath,The temperature of the reaction system was reduced to 0 ° C,A solution of thionyl chloride (71.4 g, 600 mmol)After the dropwise addition, the temperature was raised to room temperature for about 12 hours.Thin layer chromatography monitoring, when the raw material reaction is complete,Stop the reaction.After atmospheric distillation of most of the remaining thionyl chloride and methanol,Decompression in addition to thionyl chloride and methanol, cooling,To give the hydrochloride of solid tryptophan methyl ester (Isolated from air) can be used directly in the next step.

Reference： [1]Current Patent Assignee: UNIVERSITY OF SUSSEX - WO2012/131313, 2012, A1 Location in patent: Page/Page column 52
[2]Current Patent Assignee: XIHUA UNIVERSITY - CN106432237, 2017, A Location in patent: Paragraph 0032

33
[ 153-94-6 ]
[ 158932-00-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 366 - 373
[2]Chemical Biology and Drug Design,2017,vol. 90,p. 791 - 803

34
[ 153-94-6 ]
[ 171489-59-1 ]

Reference： [1]RSC Advances,2014,vol. 4,p. 1204 - 1211
[2]Patent: WO2009/37556,2009,A1
[3]Patent: CN110437228,2019,A
[4]Patent: CN111253399,2020,A

35
[ 153-94-6 ]
[ 171596-29-5 ]

Reference： [1]RSC Advances,2014,vol. 4,p. 1204 - 1211
[2]Patent: CN105348283,2016,A
[3]Patent: CN109970739,2019,A
[4]Patent: CN110437228,2019,A

36
[ 610-14-0 ]
[ 153-94-6 ]
[ 1173180-35-2 ]

Yield	Reaction Conditions	Operation in experiment
91%	With sodium hydroxide In tetrahydrofuran; water at 0℃; Ionic liquid;
90%	With sodium hydroxide In tetrahydrofuran; water at 0℃; for 2h;
1.59 g	With sodium hydroxide In tetrahydrofuran at 0℃; for 2h;

Reference： [1]Wu, Jiang-Feng; Huang, Pei-Qiang [Chinese Chemical Letters, 2020, vol. 31, # 1, p. 61 - 63]
[2]Luo, Shi-Peng; Peng, Qi-Long; Xu, Chu-Pei; Wang, Ai-E; Huang, Pei-Qiang [Chinese Journal of Chemistry, 2014, vol. 32, # 8, p. 757 - 770]
[3]Peng, Qi-Long; Luo, Shi-Peng; Xia, Xiao-Er; Liu, Liang-Xian; Huang, Pei-Qiang [Chemical Communications, 2014, vol. 50, # 16, p. 1986 - 1988]

37
[ 112-64-1 ]
[ 153-94-6 ]
N-myristoyl-D-tryptophan [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: D-tryptophan With pyridine; chloro-trimethyl-silane In dichloromethane for 4h; Stage #2: tetradecanoyl chloride In dichloromethane at 0 - 20℃; for 1.5h;	13 ExamiIel3 Pyridine (478 L, 5.94 mmol) was added dropwise to a mixture of D-tryptophan (404 mg, 1 .98 mmol) and trimethylsilyl chloride (754 L, 5.94 mmol) in dry dichloromethane (15 mL). The resulting suspension was stirred for 4 hrs until a clear solution was formed. The solution was cooled to 0 C, and then a solution of myristoyl chloride (489 L, 1 .80 mmol) in drydichloromethane (15 mL) was added dropwise. The cooling bath was removed and the mixture was stirred for 1 .5 hr at room temperature. 1 M Hydrochloric acid (20 mL) was added, the mixture was stirred for 15 mm, than the phases were separated. The organic layer was washed with 1 M hydrochloric acid (3 x 20 mL), dried over anhydrous sodium sulfate and evaporated to dryness. The residue was crystallized from dichloromethane (5mL) and hexanes (15 mL) mixture. The crystals were filtered off, washed with hexanes and dried in vacuo to give N-myristoyl-D-tryptophan as white crystals.Yield: 594 mg (80%).1 H NMR spectrum (300 MHz, CDCI3, dH): 8.34 (bs, 1 H); 7.58 (d, J7.9 Hz, 1 H); 7.35 (d, J=7.7 Hz, 1 H); 7.25-7.07 (m, 2 H); 7.01 (s, 1 H); 6.08 (d, J=7.5 Hz, 1 H); 4.99-4.85 (m, 1 H);3.45-3.25 (m, 2 H); 2.11 (t, J=7.6 Hz, 2 H); 1.62-1.41 (m, 2 H); 1.32-1.14 (m, 20 H); 0.89 (t,J=6.4 Hz, 3 H).LC-MS purity: 100% (ELSD).LC-MS Rt (Sunfire 4.6 mm x 100 mm, acetonitrile/water 50:50 to 100:0 + 0.1% FA): 7.21 mm.LC-MS mz: 414.0 (M+H)+.

Reference： [1]Current Patent Assignee: NOVO NORDISK A/S - WO2014/60447, 2014, A1 Location in patent: Page/Page column 129

38
N^α-(5-fluoro-2,4-dinitrophenyl)-L-alaninamide [ No CAS ]
[ 153-94-6 ]
[ 141779-69-3 ]

Yield	Reaction Conditions	Operation in experiment
	With Sodium hydrogenocarbonate In water monomer at 40℃; for 1.33333h;
	Stage #1: D-tryptophane With hydrogenchloride In water monomer at 120℃; for 24h; Stage #2: N^α-(5-fluoro-2,4-dinitrophenyl)-L-alaninamide With Sodium hydrogenocarbonate In water monomer; acetone at 47℃; for 1h;	2.10 Absolute configuration determination of compounds General procedure: A solution of compounds (1.5 mg) in 6 M HCl (1 ml) was heated to 120 °C for 24 h. The solution was then evaporated to dryness and the residue redissolved in H2O (100 μl) and was then placed in a 1 ml reaction vial and treated with a 2% solution of FDAA (200 μl) in acetone followed by 1.0 M NaHCO3 (40 μl). The reaction mixture was heated at 47 °C for 1 h, cooled to room temperature, and then acidified with 2.0 M HCl (20 μl). In a similar fashion, standard D- and L-amino acids were derivatized separately. The derivatives of the hydrolysates and standard amino acids were subjected to analytical HPLC analysis (Shimadzu LC-20AD, C18 column; 5 μm, 4.6 mm × 250 mm; 1.0 ml/min) at 30 °C using the following gradient program: solvent A, water + 0.2% TFA; solvent B, MeCN; linear gradient 0 min 25% B, 40 min 60% B, 45 min 100% B; UV detection at 340 nm [39].
	With Sodium hydrogenocarbonate In acetone at 40℃; for 1h;	Amino acid analysis of 1 using Marfey’s method General procedure: Compound 1 (0.5 mg) was dissolved in 1 mL of 6N HCl and heated in a sealed tube at 110 °C for 24 h. After cooling and evaporation of the remaining solvent, 100 mL of FDAA (1% N-α-(2,4-dinitro-5-fluorophenyl)-L-alaninamidein acetone), and 20 mL of 1 M NaHCO3 were added. The mixture was heated at 40 °C for 1 h and 10 mL of 2 M HCl, was added to stop the reaction. After drying in a freeze-dryer overnight, the derivatized product was dissolved in MeOH. Commercially available standard amino acids (L- and D-configuration) were treated separately with FDAA in the same way. The derivatized amino acids obtained from hydrolysis of compound 1 were analyzed using LC-MS bycomparison of the retention time and molecular weight with those of the derivatized standard amino acids (Table S1).

	Stage #1: D-tryptophane With Sodium hydrogenocarbonate In water monomer Stage #2: N^α-(5-fluoro-2,4-dinitrophenyl)-L-alaninamide In water monomer; acetone at 60℃; for 1h;
	With Sodium hydrogenocarbonate In water monomer; acetone at 37℃; for 1h;	Acid hydrolysis and Marfey’s analysis of javanicunine C (2) Acid hydrolysis and Marfey’s analysis were performed according to Helaly et al. (2018) and Capon et al. (2003) with slight modification. Briefly, 500 μL of 6 M HCl was added to 1.5 mg of javanicunine C (2). The resulting solution was kept in a sealed vial after being flushed with nitrogen and left stirring at 110 C for 24 h. The reaction mixture was then neutralized with 500 μL of 6 M NaOH and allowed to dry completely. The resulting sample was subjected to UPLC-HRMS to confirm the production of Trp (Fig. S15-S16). For the Marfey’s analysis, the hydrolysate mixture was re-dissolved in deionized water (250 μL) before adding 100 μL of sodium bicarbonate (1 M) and 500 μL of 1-fluo- ro-2-4-dinitrophenyl-5- L-alanine amide (L-FDAA) (1% in acetone). The resulting solution was kept stirring at 37 C for 1 h and then neutralized with 100 μL of 1 M HCl. Similarly, L-Trp and D-Trp were dissolved in water and treated with L-FDAA as described for the acid hydrolysate to afford L-FDAA standards. UPLC-HRMS analysis of the Marfey’s de- rivatives of compound 2, L-Trp, and D-Trp was performed using an LTQ-Orbitrap XL mass spectrometer connected to a Waters Acquity UPLC system (Fig. S17).
	With Sodium hydrogenocarbonate In aq. phosphate buffer

Reference： [1]Schubert, Vivien; Di Meo, Florent; Saaidi, Pierre-Loic; Bartoschek, Stefan; Fiedler, Hans-Peter; Trouillas, Patrick; Suessmuth, Roderich D. [Chemistry - A European Journal, 2014, vol. 20, # 17, p. 4948 - 4955]
[2]Nishanth Kumar; Mohandas; Nambisan, Bala [Peptides, 2014, vol. 53, p. 48 - 58]
[3]Zeng, Yanbo; Wang, Hao; Kamdem, Ramsay S.T.; Orfali, Raha S.; Dai, Haofu; Makhloufi, Gamall; Janiak, Christoph; Liu, Zhen; Proksch, Peter [Tetrahedron Letters, 2016, vol. 57, # 27-28, p. 2998 - 3001]
[4]Chen, Ziming; Huang, Hongbo; Ju, Jianhua; Luo, Minghe; Song, Xiaoxian; Wang, Xin; Zang, Ruochen [Journal of Natural Products, 2019, vol. 82, # 9, p. 2594 - 2600]
[5]Al Subeh, Zeinab Y.; Raja, Huzefa A.; Burdette, Joanna E.; Falkinham, Joseph O.; Hemby, Scott E.; Oberlies, Nicholas H. [Phytochemistry, 2021, vol. 189]
[6]Doyon, Tyler J.; Buller, Andrew R. [Journal of the American Chemical Society, 2022, vol. 144, # 16, p. 7327 - 7336]

39
[ 1446358-48-0 ]
[ 153-94-6 ]
C₂₈H₂₁F₂N₇O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
16%	With triethylamine In tetrahydrofuran; water at 100℃; for 18h;	1 General procedure: General procedure B A solution of amino nucleophile (3 equiv.), triethylamine (10 equiv.), and Intermediate 1 (1 equiv.) was stirred in dioxane and water (2:1 ratio) at 90 °C until complete consumption of starting material was observed by LC/MS. The solution was diluted withiN hydrochloric acid and dichloromethane. The layers were then separated and thelayer was extracted with dichloromethane. The organics were combined, dried over magnesium sulfate, filtered, and the solvent was removed in vacuo. Purification yielded theproduct. The title compound was prepared following general procedure B, except D-tryptophan was the amine reactant and the contents were heated at 100 °C for 18 h as a solution in THF/water (2:1). The contents were treated with 3N HC1 solution, solvent was removed in vacuo, and the resulting solid was washed with H20, then purified via reverse phase HPLC utilizing a 5-75 % acetonitrile/water gradient to deliver the desired compound, Compound 1-108 (3.5 mg, 16 %) as a clear oil.1H-NMR (500 MHz, CD3OD) ö 8.85 (d, 1 H), 8.16 (d, 1 H), 7.69 (d, 1 H), 7.33-7.27 (m, 1 H),7.17 (d, 1 H), 7.13-7.05 (m, 4 H), 7.01-6.96 (m, 1 H), 6.95-6.89 (m, 3 H), 5.97 (s, 2 H), 5.50 (dd, 1 H), 3.70 (dd, 1 H), 3.28 (d, 1 H).

Reference： [1]Current Patent Assignee: CYCLERION THERAPEUTICS INC - WO2014/144100, 2014, A2 Location in patent: Paragraph 00274

40
[ 5255-17-4 ]
[ 153-94-6 ]
N-(3β-hydroxy-Δ⁵-cholen-24-oyl)-D-tryptophan [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	Stage #1: 3β-hydroxy-5-cholenoic acid With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0℃; for 0.416667h; Inert atmosphere; Stage #2: D-tryptophan In N,N-dimethyl-formamide at 0 - 20℃; for 16h; Inert atmosphere; chemoselective reaction;	General procedure for the coupling of cholenic acid 4 to amino acids General procedure: To a stirred solution of cholenic acid (183.1mg, 0.489 mmol) in DMF (5.0 mL) at 0 °C, DIPEA (N,N-diisopropyl-N-ethylamine, 200 μL, 1.15 mmol) is added. To the obtained suspension, TBTU (O-(Benzotriazol-1-yl)-N,N,N',N',-tetramethyluronium tetrafluoroborate, 195.2 mg, 0.515 mmol) is added, and the mixture is stirred at 0 °C for additional 25 minutes, when a perfectly clear solution is obtained. The appropriate aminoacid (0.494 mmol) is then added and the mixture is allowed reaching room temperature while stirring for a total of 16 hours. The mixture is poured over AcOEt (50 mL) and acidified with 2% aqueous H2SO4. The aqueous layer is discarded, and the organic layer is washed at first with half-saturated brine and then brine. The organic phase is dried over Na2SO4 and evaporated under reduced pressure. The crude material thus obtained is purified by silica gel column chromatography eluting at first with a 5% solution of methanol in dichloromethane, then with a mixture of DCM:MeOH:AcOH = 95:5:0.5 v/v/v.

Reference： [1]Castelli, Riccardo; Tognolini, Massimiliano; Vacondio, Federica; Incerti, Matteo; Pala, Daniele; Callegari, Donatella; Bertoni, Simona; Giorgio, Carmine; Hassan-Mohamed, Iftiin; Zanotti, Ilaria; Bugatti, Antonella; Rusnati, Marco; Festuccia, Claudio; Rivara, Silvia; Barocelli, Elisabetta; Mor, Marco; Lodola, Alessio [European Journal of Medicinal Chemistry, 2015, vol. 103, p. 312 - 324]

41
[ 5616-32-0 ]
[ 153-94-6 ]
C₁₄H₁₆N₄O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at 20℃; for 5h;	1 Example 1 Example 1 To a 1L three-necked flask was added 200mL of tetrahydrofuran, 20g D-tryptophan, 7.7g methylaminoacetonitrile, 38.2g EDC · HCl and 1g 4-dimethylaminopyridine. The reaction was stirred at room temperature for 5 hours. After completion of the reaction, 300mL of ethyl acetate and 300mL water was added. The ethyl acetate layer was washed with 200mL saturated sodium chloride and stirred. Still stratification of the ethyl acetate layer was distilled under reduced pressure at 30°C to a volume of about 200ml. The solution was recrystallized with 700ml of petroleum ether, filtered and vacuum dried at 40°C to give 22.25g of compound III. HPLC purity 98%, Yield 91%.

Reference： [1]Current Patent Assignee: ZHEJIANG YONGNING PHARMA - CN105348283, 2016, A Location in patent: Paragraph 0031; 0032

42
[ 153-94-6 ]
[ 343-94-2 ]

Yield	Reaction Conditions	Operation in experiment
23.3%	With pyridoxal hydrochloride In aq. buffer at 15℃; for 18h;	Synthesis of Tryptamine Hydrochloride Mixtures of equimolar 0.01 pyridoxal hydrochloride and D-tryptophan in a 90% buffer solution were kept for 18 h at T = 15 °C. In preparing the solutions, the mixtures turned an intense yellow and changed their color to orange over time. The color then became less intense, and a white precipitate formed. The precipitate was filtered off, washed with alcohol, and dried to a constant weight. The yield was 0.0088 g (23.3%); m > 210 °C (the precipitate blackened as it decomposed). The product yielded a qualitative reaction for Cl- with a solution of AgNO3 and aqualitative reaction with Br2 (violet). The final product was poorly soluble in alcohol (IR spectrum (KBr), ν, cm-1: 3150-3350 (NH2), 2250-2700 (>NH), 1625, 1580 (C=C); UV spectrum, λmax: 280 nm).

Reference： [1]Pishchugin; Tuleberdiev [Russian Journal of Physical Chemistry, 2017, vol. 91, # 10, p. 1851 - 1854][Zh. Fiz. Khim., 2017, vol. 91, # 10, p. 1648 - 1652,5]

43
[ 107-18-6 ]
[ 153-94-6 ]
H-D-Trp-OAll [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90.3%	With toluene-4-sulfonic acid In toluene at 25 - 95℃;	2; 5 Example 5: Preparation of Boc-Tyr-D-Trp-OAll (13) D-Tryptophan (100 g), and PTSA.H20 (186.28 g) were added to allyl alcohol (1000 ml) stirred at 25 to 35°C, followed by addition of toluene (500ml). The resulting mixture was stirred at 80-95°C till completion of reaction, as monitored by TLC. After completion, the mass was cooled, and 5% aqueous sodium bicarbonate solution was added to it. Extraction with ethyl acetate followed by separation and concentration of the organic layer gave a residue containing H-D-Trp-OAll (11). Yield: 108.01 g (90.3%) Purity: > 95% (HPLC)
90%	With toluene-4-sulfonic acid In toluene at 25 - 95℃;	5 Example 5: Preparation of Boc-Tyr-D-Trp-OAll (13) Example 5: Preparation of Boc-Tyr-D-Trp-OAll (13) (0078) D-Tryptophan (150 g), and PTSA.FLO (280 g) were added to allyl alcohol (1500 ml) stirred at 25 to 35 °C, followed by addition of toluene (500ml). The resulting mixture was stirred at 80-95 C till completion of reaction, as monitored by TLC. After completion, the mass was cooled, and 5% aqueous sodium bicarbonate solution was added to it. Extraction with ethyl acetate followed by separation and concentration of the organic layer gave a residue containing H-D-Trp-OAll (11). Yield : 162 g, 90 %, Purity : 98% (HPLC) (0079) Boc-Tyr-OH (12, 173 g) was added to the stirred mixture of H-D-Trp-OAll (11.150 g) and DMF (450 ml) at 25 to 35°C, followed by addition of HOBt (104 g). NMM (75 ml) and EDAC.HCl (142 g). The reaction mixture was stirred at 10 to 30°C, till completion, as monitored by TLC. After completion, the reaction mass was quenched with 0.5N HCl. The precipitated solid was filtered, treated with 5% aqueous sodium carbonate solution, filtered again and dried to give Boc-Tyr-D-Trp-OAll (13). (0080) Yield : 280 g, 90%, Purity : 95% (HPLC)
90.2%	With toluene-4-sulfonic acid In toluene at 25 - 95℃;	5 Example 5: Preparation of Boc-Tyr-D-Trp-OAll (16) D-Tryptophan (H-D-Trp-OH, 13, 100.0 g), and PTSA.H20 (186.3 g) were added to allyl alcohol (1000 ml) stirred at 25 to 35°C, followed by addition of toluene (500ml). The resulting mixture was stirred at 80 to 95°C till completion of reaction, as monitored by TLC, HPLC. After completion, the mass was cooled and 5% aqueous sodium bicarbonate solution was added to it. Extraction with ethyl acetate followed by separation and concentration of the organic layer gave a residue containing H-D-Trp-OAll (14). Yield: 108.01 g (90.3%), Purity: > 95% (HPLC)

Reference： [1]Current Patent Assignee: EMCURE PHARMACEUTICALS LTD. - WO2017/178950, 2017, A1 Location in patent: Page/Page column 8; 16
[2]Current Patent Assignee: EMCURE PHARMACEUTICALS LTD. - WO2017/212390, 2017, A1 Location in patent: Page/Page column 18-19
[3]Current Patent Assignee: EMCURE PHARMACEUTICALS LTD. - WO2019/77507, 2019, A1 Location in patent: Page/Page column 18

44
[ 67-56-1 ]
[ 153-94-6 ]
D-tryptophan ethyl ester hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With thionyl chloride at 0 - 22℃; for 26h;	General Method to Obtain D-AminoAcid Methyl Ester Hydrochlorides General procedure: To a suspension of 5 g of D-amino acid in 100 mLdry methanol at 0-5°, 8-10 mL thionyl chloridewere added dropwise, the mixture was stirred for 2 hand kept at 20-22° for 24 h. The solvent was evaporatedunder vacuum at 30-40°, the residue wasmixed with dry ether, filtered off, dried, and recrystallizedfrom methanol-ether mixture.

Reference： [1]Fayrushina; Baltina; Baltina; Konovalova; Petrova; Eropkin, M. Yu. [Russian Journal of Bioorganic Chemistry, 2017, vol. 43, # 4, p. 456 - 462][Bioorg. Khim., 2017, vol. 43, # 4, p. 427 - 434,8]

45
[ 14389-12-9 ]
copper(II) choride dihydrate [ No CAS ]
[ 153-94-6 ]
[Cu(D-tryptophanate)(5-(4-pyridyl)tetrazolate)]n [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide at 50℃; for 168h;

Reference： [1]Mendiratta, Shruti; Tseng, Tien-Wen; Luo, Tzuoo-Tsair; Chen, Chi; Huang, Chia-Yuan [Crystal Growth and Design, 2018, vol. 18, # 5, p. 2672 - 2676]

46
[ 120-72-9 ]
[ 56-45-1 ]
[ 153-94-6 ]

Yield	Reaction Conditions	Operation in experiment
69%	Stage #1: indole; L-serin With Salmonella enterica tryptophan synthase In methanol; aq. phosphate buffer at 37℃; Enzymatic reaction; Stage #2: With (2R)-aspartic acid In methanol; aq. phosphate buffer Stage #3: In aq. phosphate buffer; deuteromethanol at 37℃; Enzymatic reaction; stereoselective reaction;

Reference： [1]Parmeggiani, Fabio; Rué Casamajo, Arnau; Walton, Curtis J. W.; Galman, James L.; Turner, Nicholas J.; Chica, Roberto A. [ACS Catalysis, 2019, vol. 9, # 4, p. 3482 - 3486]

47
[ 73-22-3 ]
[ 153-94-6 ]

Yield	Reaction Conditions	Operation in experiment
94 % ee	With (2R)-aspartic acid In methanol; aq. phosphate buffer at 37℃; for 6h; Enzymatic reaction; stereoselective reaction;
> 99 % ee	With IvoA acetyltransferase; ATP; magnesium chloride In aq. phosphate buffer at 20℃; for 12h; enantioselective reaction;
	Multi-step reaction with 2 steps 1.1: acetonitrile / 25 h / 20 - 60 °C 1.2: 12 h / 40 °C 2.1: benzylamine hydrochloride / isopropyl alcohol; water / 1 h / 20 °C

> 99 % ee

With dipotassium hydrogenphosphate; ATP; magnesium chloride In aq. buffer at 20℃; for 12h; Enzymatic reaction;

Reference： [1]Parmeggiani, Fabio; Rué Casamajo, Arnau; Walton, Curtis J. W.; Galman, James L.; Turner, Nicholas J.; Chica, Roberto A. [ACS Catalysis, 2019, vol. 9, # 4, p. 3482 - 3486]
[2]Hai, Yang; Jenner, Matthew; Tang, Yi [Journal of the American Chemical Society, 2019, vol. 141, # 41, p. 16222 - 16226]
[3]Chin, Jik; Fu, Rui; Lough, Alan J.; So, Soon Mog [Angewandte Chemie - International Edition, 2020, vol. 59, # 11, p. 4335 - 4339][Angew. Chem., 2020, vol. 132, # 11, p. 4365 - 4369,5]
[4]Current Patent Assignee: UNIVERSITY OF CALIFORNIA - WO2021/55696, 2021, A1 Location in patent: Page/Page column 6; 10-11; 17

48
[ 1256350-54-5 ]
[ 153-94-6 ]
C₃₇H₃₄N₂O₈ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48.4%	Stage #1: 3-(3,5-dimethoxyphenyl)-6-methoxy-2-(4-methoxyphenyl)benzofuran-4-carboxylic acid With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 0.333333h; Stage #2: D-tryptophan In dichloromethane at 20℃; for 4h;	26 Synthesis Method B General procedure: Compound 1d (100 mg, 0.23 mmol) was dissolved in 50 mL of dry dichloromethane.DMAP (33.7 mg, 0.28 mmol) and EDCI (53.0 mg, 0.28 mmol) were added in that order.After stirring for 20 minutes,Add the amine compound (1.2 equiv) and stir at room temperature for 4 h.The TLC monitors the disappearance of the starting material and stops the reaction.The reaction solution is concentrated under reduced pressure, and the residue is separated by silica gel.The corresponding product was obtained.

Reference： [1]Current Patent Assignee: CHINESE ACADEMY OF MEDICAL SCIENCES - CN109721579, 2019, A Location in patent: Paragraph 0196; 0203; 0268-0271

49
xenematide G [ No CAS ]
[ 72-19-5 ]
[ 44902-02-5 ]
[ 153-94-6 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In water; at 120℃; for 3h;	General procedure: Compounds 1 and 2 (1mg each) were hydrolysed with 6MHCl (1ml) at 120 C for 3 h. The solutions were then evaporatedto dryness, and the residues were re-dissolved in 1mlof water and dried on a rotary evaporator. Next, 100 mul of 1Msodium bicarbonate was added to each residue to form solutions.Amino acid standards were also individually dissolvedin 100 mul of 1M sodium bicarbonate at concentrations of1mgml-1. The D, L-aminoheptanoic acid were purchasedfrom Aladdin Biochemical Technology and J&K Scientific.Thirty-five microlitres of Nalpha-(2,4-dinitro-5-fluorophenyl)-L-alaninamide (L-FDAA, Marfey?s Reagent, for threonine,leucine and tryptophan) [26] and 60mul Nalpha-(2,4-dinitro-5-fluorophenyl)-D/L-leucinamide (D/L-FDLA, advanced Marfey?sreagent, for alpha-aminoheptanoic acid) [27] in acetone(10mgml-1) was added to each solution. The solutions wereincubated in a water bath at 55 C for 1 h. After cooling toroom temperature, each solution was dissolved in MeCN forHPLC analysis. At 26 C, MeCN/H2O containing 0.1%HCOOH was used as mobile phase using the following gradient:0-5min, 20% MeCN; 5-35 min, 20-60% MeCN;35-40min, 60-100% MeCN and 40-50 min, 100-20%MeCN. The flow rate was 1 ml min-1 with UV detection at340 nm. The HPLC results for the amino acids were comparedto the results of the standard samples [26].

Reference： [1]Journal of Antibiotics,2019

50
[ 59259-90-4 ]
[ 153-94-6 ]
[ 406938-39-4 ]

Yield	Reaction Conditions	Operation in experiment
86%	With trifluoroacetic acid In 5,5-dimethyl-1,3-cyclohexadiene at 120℃;	1; 5 Example 5 Weigh 200 g of the compound of formula 1 (1.02 mol)And 204.2 g of the compound of formula 2 (1.0 mol)Stir in a 2L three-neck bottle.Add 1500 mL of xylene and 228 g of trifluoroacetic acid (2.0 mol),Heat to 120 degrees Celsius.The reaction to the compound of formula 2 is less than 1.0%, and the temperature is lowered to 10 degrees Celsius.Filtering, drying under reduced pressure at 60 ° C to obtain 290 g of compound 3,The molar yield relative to the compound of formula 2: 86%, purity 98.7%.

Reference： [1]Current Patent Assignee: WATERSTONE PHARMACEUTICALS WUHAN - CN109970739, 2019, A Location in patent: Paragraph 0011; 0016

51
[ 35718-08-2 ]
[ 153-94-6 ]
C₁₅H₁₄N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	With sodium hydroxide In water at 0 - 20℃; for 0.5h;	V.d d. Preparation of intermediate 18 D-Tryptophane 17 (1.00 g, 4.89 mmol, 1.0 eq.) was suspended in water (10 ml_). Solubilization occurs after sodium hydroxide (0.78 g, 19.56 mmol, 4.0 eq.) addition. Reaction mixture was cooled down at 0°C, and propargylchloroformate 5 (0.64 g, 5.39 mmol, 0.52 ml_, 1.1 eq.) was added dropwise. Reaction mixture was allowed to warm up to room temperature for 30 minutes. Reaction mixture was acidified with (12N) hydrochloric acid solution, extracted with ethyl acetate (3 x 100 ml_), dried over magnesium sulfate and solvents were evaporated under vacuum. The residue was purified by flash chromatography [Biotage ; column AIT 40g; eluant: Cyclohexane / EtOAc; gradient: 100/0 -> 0/100 (12 CV)] affording compound 18 (530 mg, 38% yield) as a white foam.

Reference： [1]Current Patent Assignee: CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE; UNIVERSITY OF STRASBOURG; CENTRE HOSPITALIER UNIVERSITAIRE DE BESANCON; UNIVERSITY OF FRANCHE-COMTE - WO2019/243273, 2019, A1 Location in patent: Page/Page column 78; 80

52
C₁₅H₁₅N₃*C₁₈H₁₄Cl₂N₂O₃ [ No CAS ]
[ 153-94-6 ]

Yield	Reaction Conditions	Operation in experiment
95%	With benzylamine hydrochloride In water; isopropyl alcohol at 20℃; for 1h;

Reference： [1]Chin, Jik; Fu, Rui; Lough, Alan J.; So, Soon Mog [Angewandte Chemie - International Edition, 2020, vol. 59, # 11, p. 4335 - 4339][Angew. Chem., 2020, vol. 132, # 11, p. 4365 - 4369,5]

53
[ 120-57-0 ]
[ 153-94-6 ]
[ 406938-39-4 ]

Yield	Reaction Conditions	Operation in experiment
88.5%	Stage #1: piperonal; D-tryptophan With trifluoroacetic acid at 30 - 40℃; for 25h; Inert atmosphere; Stage #2: With hydrogenchloride In water at 40 - 50℃; for 17h; Inert atmosphere;	1.S2-1.S3; 2.S2-2.S3; 3.S2-3.S3; 4.S2-4.S3; 5.S2-5.S3; 6.S2-6.S3; 7.S2-7.S3; 8.S2-8.S3 S2. Add D-tryptophan and trifluoroacetic acid to the piperonal solution and react at 30-40°C for 25h in a nitrogen atmosphere.Then wash and neutralize the excess trifluoroacetic acid with aqueous sodium bicarbonate solution, and remove the aqueous phase in layers to obtain an intermediate solution;S3. Take the intermediate solution, distill off the methylene chloride, add concentrated hydrochloric acid and water, and react at 40-50°C for 17h in a nitrogen atmosphere.Decrease the temperature to 0-10, crystallize, filter, wash with water, and dry to obtain tadalafil intermediate,Among them, the weight ratio of dichloromethane, catalyst, piperitol, D-tryptophan, trifluoroacetic acid, water, and concentrated hydrochloric acid is 120:0.6:10:15:15:15:3.

Reference： [1]Current Patent Assignee: PINGGUANG PHARMACEUTICAL - CN111116583, 2020, A Location in patent: Paragraph 0037; 0039; 0042-0044; 0047-0049; 0052-0054; 0057

54
[ 53406-00-1 ]
[ 153-94-6 ]
C₁₇H₁₆N₃O₃⁽¹⁺⁾ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47.8%	With triethylamine In methanol at 20℃; for 24h;	17 Example 17 To the 2 mL methanol solution containing D-Trp (D-Trp, 224.6 mg, 1.1 mmol), dropwise add 1-(2,4-dinitrophenyl)-3-carbamoylpyridine chloride (324.7mg, 1mmol) in 2 mL of methanol solution. After the addition is complete, add 1mmol of triethylamine, add in three times at 0h, 4h, and 9h respectively. After stirring for 24h at room temperature, TLC detects that raw material 1-(2, The reaction of 4-dinitrophenyl)-3-carbamoylpyridine chloride is complete.The insoluble matter in the reaction solution was removed by filtration, the filtrate was concentrated under reduced pressure to remove the solvent, and purified by silica gel column chromatography to obtain the product D-Trp-NAD (165 mg, 47.8%).

Reference： [1]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES; Dalian Institute of Chemical Physics (in: CAS) - CN111217744, 2020, A Location in patent: Paragraph 0062; 0063

55
[ 108-31-6 ]
[ 153-94-6 ]
C₁₅H₁₄N₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95.69%	In cyclohexane at 40℃; for 3.5h;	3 Example 3 Take 2.94g (30.0mmol) maleic anhydride and 20mL cyclohexane and add it to a 50mL reaction bottle, stir and heat, and add D-tryptophan 2.04g (10.0mmol) at a constant temperature of 40 °C after it is completely dissolved, and track the reaction progress by thin layer chromatography. After the end of the 3.5h reaction, the solvent was removed by rotational evaporation, the solid crude product was dissolved with ethyl acetate, washed several times with 0.1M sodium bicarbonate solution, ethyl acetate extracted, the organic layer was dried with anhydrous sodium sulfate, the solvent was removed by reduced pressure distillation to obtain a reddish-brown solid, and the product was recrystallized with absolute ethanol to obtain the product, the yield was 95.69%, and the structural formula of the product was (I.-3).

Reference： [1]Current Patent Assignee: CHINA AGRICULTURAL UNIVERSITY - CN113861096, 2021, A Location in patent: Paragraph 0045-0047

56
[ 1680-36-0 ]
[ 153-94-6 ]
C₂₀H₂₈N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87.63%	In cyclohexanone at 80℃; for 24h;	6 Example 6 In a 50mL three-mouth flask, 2.98g (10.0mmol) of nonanoic anhydride, 20mL cyclohexanone and 2.04g (10.0mmol) D-tryptophan were added to a 50mL three-mouth flask, heated to 80 °C and stirred for 24h, the reaction ended, washed with 0.1M sodium hydroxide solution, ethyl acetate extracted, distilled under reduced pressure to remove the solvent to obtain a reddish-brown viscous solid, and recrystallized with absolute ethanol to obtain the product. The yield was 87.63%, and the structural formula of the product was (I.-6).

Reference： [1]Current Patent Assignee: CHINA AGRICULTURAL UNIVERSITY - CN113861096, 2021, A Location in patent: Paragraph 0054-0056

57
[ 407-25-0 ]
[ 153-94-6 ]
[ 22220-03-7 ]

Yield	Reaction Conditions	Operation in experiment
95.49%	In acetonitrile at 20℃; for 0.5h;	8 Example 8 In a 50mL three-mouth flask was added 4.20g (20.0mmol) of trifluoroacetic anhydride, 10mL acetonitrile and 2.04g (10.0mmol) D-tryptophan, stirred at room temperature for 0.5h, after the reaction was completed, the solvent was removed by reduced pressure distillation, the solid crude product was washed with 0.1M sodium carbonate solution, dichloromethane extraction, the organic layer was dried with sodium anhydrous sulfate, the solvent was removed by vacuum distillation to obtain a reddish-brown solid, and ethanol was recrystallized. The yield was 95.49%, and the structural formula of the product was (I.-8).

Reference： [1]Current Patent Assignee: CHINA AGRICULTURAL UNIVERSITY - CN113861096, 2021, A Location in patent: Paragraph 0060-0062

58
[ 105827-91-6 ]
[ 153-94-6 ]
C₁₅H₁₄ClN₃O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83.29%	With pyridine In dimethyl sulfoxide at 60℃;	12 Example 12 To the 50mL three-mouth flask was added 1.02g (5.0mmol) D-tryptophan, dissolved in 25mL DMSO, after adding 0.69g (5.0mmol) pyridine, under the condition of stirring, adding 5mL2-chloro-5- (chloromethyl) thiazole (0.84g, 5.0mmol) of DMSO solution, heated to 60 °C overnight reaction, TLC detection, raw materials after all the reaction is complete, add a large amount of ethyl acetate, filtered to collect solids, ethanol recrystallization to obtain reddish-brown powder. The yield was 83.29%, and the structural formula of the product was (I.-10).

Reference： [1]Current Patent Assignee: CHINA AGRICULTURAL UNIVERSITY - CN113788801, 2021, A Location in patent: Paragraph 0086-0088

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	153-94-6	MDL No. :	MFCD00005647
Formula :	C₁₁H₁₂N₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	QIVBCDIJIAJPQS-SECBINFHSA-N
M.W :	204.23 g/mol	Pubchem ID :	9060
Synonyms :

Num. heavy atoms :	15
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.18
Num. rotatable bonds :	3
Num. H-bond acceptors :	3.0
Num. H-bond donors :	3.0
Molar Refractivity :	57.36
TPSA :	79.11 Å²

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-8.3 cm/s

Log Po/w (iLOGP) :	0.98
Log Po/w (XLOGP3) :	-1.06
Log Po/w (WLOGP) :	1.12
Log Po/w (MLOGP) :	-1.66
Log Po/w (SILICOS-IT) :	1.53
Consensus Log Po/w :	0.18

[ CAS No. 153-94-6 ]

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

Log S (ESOL) :	-0.68
Solubility :	42.2 mg/ml ; 0.207 mol/l
Class :	Very soluble
Log S (Ali) :	-0.11
Solubility :	158.0 mg/ml ; 0.772 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.76
Solubility :	0.357 mg/ml ; 0.00175 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.09

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

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

[ CAS No. 153-94-6 ]

Quality Control of [ 153-94-6 ]

Related Doc. of [ 153-94-6 ]

Product Details of [ 153-94-6 ]

Calculated chemistry of [ 153-94-6 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 153-94-6 ]

Application In Synthesis of [ 153-94-6 ]

[ 153-94-6 ] Synthesis Path-Upstream 1~4

[ 153-94-6 ] Synthesis Path-Downstream 1~58

Similar Product of [ 153-94-6 ]

Related Functional Groups of [ 153-94-6 ]

Amino Acid Derivatives

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Similar Product of
[ 153-94-6 ]

Related Functional Groups of
[ 153-94-6 ]