Name: 6306-54-3|(S)-2-(1,3-Dioxoisoindolin-2-yl)-3-methylbutanoic acid|98%
Brand: Ambeed
SKU: A599961
Price: 7.0 USD
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1
[ 85-44-9 ]
[ 72-18-4 ]
[ 6306-54-3 ]

Yield	Reaction Conditions	Operation in experiment
100%	at 135℃;
98%	at 140℃; for 0.166667h;
98%	In melt at 140℃; for 0.25h;

97%	at 170℃; for 1h;	(S)-2-(1,3-dioxoisoindolin-2-yl)-3-methylbutanoic acid (L-N-Phthaloylvaline, 27) and methyl (S)-2-(1,3-dioxoisoindolin-2-yl)-3-methylbutanoate (L-N-Phthaloylvaline methyl ester, S6) A mixture of L-leucine (1.17 g, 10.0 mmol) and phthalic anhydride (1.0 equiv, 1.48 g, 10.0mmol) was stirred and heated at 170 °C for 1 h under reduced pressure. Cooling thereaction mixture to rt afforded spectroscopically pure 27 (2.41 g, 9.75 mmol, 97%). 27 wasused for the next step without further purification as follows: to 27 (0.99 g, 4.00 mmol) inMeOH (40mL) was added thionyl chloride (4.0 equiv, 1.90 g, 16.0 mmol) at 0 °C dropwise. The resultingmixture was warmed to rt and stirred overnight. The reaction mixture was concentrated in vacuo, silicagel column chromatography (hexane/EtOAc = 5/1, v/v) gave S6 (0.94 g, 90%) as a colorless liquid. TheNMR data of 27 and S6 were consistent with those previously reported.
95%	In water for 0.5h; microwave irradiation;
83%	With acetic acid for 5h; Reflux;
80%	With triethylamine In toluene for 16h; Dean-Stark; Reflux;	3.1 Step 1 To a 1-necked round-bottom flask (1 L) equipped with a condenser and Dean-Stark apparatus was charged with L-valine (23.4 g, 0.2 mole), phthalic anhydride (29.6 g, 0.2 mole), toluene (300 mL) and Et3N (2.6 mL) in that order. The resulting mixture was refluxed for 16 hrs until no more H20 was produced. H20 (300 mL) was added to the cooled solution and layers were separated. Organic layer was further washed with brine, dried and concentrated. The crude was crystallized from EtOAc /hexanes (80 mL/200 mL) to give (S)-2-(l,3-dioxoisoindolin-2-yl)-3- methylbutanoic acid (39.0 g, 80%) as a white solid.
75%	With triethylamine In toluene for 18h; Reflux;
75%	at 121℃; for 1h;	2 (2S)-3-Methyl-2-(1,3-dioxo-2-benzazole-2-yl)butanoic acid 3b The (S)-amino acids 1a-c and 1e (1mmol, 1equiv) and phthalic anhydride (1.5mmol, 1.5equiv) were heated together at 130-160°C. After completion of the reaction, the unreacted phthalic anhydride was scraped off from the walls of the flask and the crude acid that remained in the flask was purified by crystallization, from different solvents, to afford pure crystals of 3a-c, e (Table 4). 4.1.2 (2S)-3-Methyl-2-(1,3-dioxo-2-benzazole-2-yl)butanoic acid 3b White needles. (5.12 g, 75%), mp 121 °C, Rf: 0.5 (EtOAc); [α]D29 = +28.5 (c 1.5, EtOAc); νmax (cm-1): 3489 (br s, O-H), 1732 (br s, both carboxylic and amido C=O); log ε (λmax, nm): 3.3449 (298.5); δH (400 MHz, CD3OD, in ppm): 0.88 (3H, d, J = 6.8 Hz, H4), 1.14 (3H, d, J = 6.4 Hz, CH3 at C3), 2.69 (1H, 8 signals with 1:7:21:35:35:21:7:1 ratio, J = 6.8 Hz, H3), 4.52 (1H, d, J = 8 Hz, H2) and 7.82-7.89 (4H, m, aromatic Hs); LR EIMS m/z in amu (% abundance): 247 (13) [M]+⩽, 205 (14) [M-propene]+, 204 (10) [M-iPr⩽]+, 203 (34) [M-CO2, A]+⩽, 202 (1 0 0) [M-⩽OH-CO]+⩽ and 160 (35) [A-iPr⩽]+.
75%	In neat (no solvent) for 1h; Heating;
73%	for 0.5h; Heating;
70%	With triethylamine In toluene at 130℃; Dean-Stark;
50%	In N,N-dimethyl-formamide for 0.0333333h; Microwave irradiation;
	at 150 - 180℃;
	at 150 - 180℃; for 0.5h;
	With potassium hydroxide 2.) MeOH; Multistep reaction;
	at 140℃;
	In N,N-dimethyl-formamide at 100℃; for 12h;
	In toluene for 20h; Heating;
	With acetic acid at 150℃; for 0.166667h; Microwave irradiation;
	With acetic acid for 12h; Reflux;
	In N,N-dimethyl-formamide Reflux;
	With triethylamine In toluene Heating;
	With triethylamine In toluene Reflux; Dean-Stark;
	With acetic acid Reflux; Schlenk technique;
	With acetic acid Schlenk technique; Reflux;
	With triethylamine In toluene for 24h; Reflux;	15 Synthesis of E Phthalic anhydride is added to L-valine (D) in toluene with presence of triethyl amine. Afier reflux for 24 hours, the solvent is removed by evaporation and the residue is purifiedby recrystallization from ethanol.
	With acetic acid Reflux; Schlenk technique; Inert atmosphere;
	With triethylamine In toluene for 4h; Dean-Stark; Reflux;	13 General Peptide Synthesis Procedures:N-Protection with Phthalimide General procedure: Amino acid (13.5 mmol, 1.0 equiv), phthalic anhydride (13.5 mmol, 1.0 equiv), and triethylamine (1.35 mmol, 0.1 equiv) were dissolved in toluene (70 mL) in an oven dried round bottom flask equipped with a stir bar and a Dean-Stark apparatus. The reaction mixture was heated to reflux for 4 h. Upon cooling, the reaction mixture was concentrated. The residue was dissolved in EtOAc, transferred to a separatory funnel, and washed with 1 M HCl. The organic layer was dried with MgSO4, filtered through Celite, and concentrated. The products were purified via column chromatography on silica gel eluting with hexanes/EtOAc.
	With triethylamine In toluene Reflux; Inert atmosphere;
	With triethylamine
	With triethylamine In toluene Reflux;
	at 170℃;	Reaction condition a: If the compound of formula If is added in a molar ratio of 1: 1.5,The reaction at 170 degrees and agitated conditions is ‘abdominal drunk:

Reference： [1]Griesbeck, Axel G.; Mauder, Harald [Angewandte Chemie, 1992, vol. 104, # 1, p. 97 - 99]
[2]Griesbeck, Axel G.; Mauder, Harald; Mueller, Ingrid [Chemische Berichte, 1992, vol. 125, # 11, p. 2467 - 2476]
[3]Griesbeck, Axel G.; Hirt, Joachim; Peters, Karl; Peters, Eva-Maria; Schnering, Hans-Georg von [Liebigs Annalen, 1995, # 4, p. 619 - 624]
[4]Baran, Phil S.; Chen, Longrui; Chen, Miao; Hoshikawa, Tamaki; Kawamata, Yu; Li, Chao; Mykhailiuk, Pavel; Nakamura, Hugh; Peters, Byron K.; Reisberg, Solomon H.; Shibuguchi, Tomoyuki; Takahira, Yusuke [Synlett, 2019, vol. 30, # 10, p. 1178 - 1182]
[5]Shendage, Deepak M.; Froehlich, Roland; Haufe, Guenter [Organic Letters, 2004, vol. 6, # 21, p. 3675 - 3678]
[6]Tukhtaev; Yusupov; Vinogradova [Egyptian Journal of Chemistry, 2021, vol. 64, # 6, p. 3049 - 3058]
[7]Current Patent Assignee: THE ROSKAMP INST - WO2020/154420, 2020, A2 Location in patent: Page/Page column 33
[8]Wixey, James S.; Ward, Benjamin D. [Chemical Communications, 2011, vol. 47, # 19, p. 5449 - 5451]
[9]Saddiqa, Aisha; Raza, Abdul R.; Black, David Stc.; Kumar, Naresh [Tetrahedron Asymmetry, 2014, vol. 25, # 9, p. 736 - 743]
[10]Raza, Abdul Rauf; Saddiqa, Aisha; Çakmak, Osman [Chirality, 2015, vol. 27, # 12, p. 951 - 957]
[11]Sharma, Renu; Nagar, Meena [Phosphorus, Sulfur and Silicon and the Related Elements, 2006, vol. 181, # 12, p. 2863 - 2875]
[12]Vicens, Laia; Bietti, Massimo; Costas, Miquel [Angewandte Chemie - International Edition, 2021, vol. 60, # 9, p. 4740 - 4746][Angew. Chem., 2021, vol. 133, # 9, p. 4790 - 4796,7]
[13]Leite, Ana Cristina Lima; Barbosa, Fabio Fernandes; Cardoso, Marcos Verissimo De Oliveira; Moreira, Diogo R. M.; Coelho, Lucas Cunha D.; Da Silva, Elany Barbosa; Filho, Gevanio Bezerra De Oliveira; De Souza, Valdenia Maria Oliveira; Pereira, Valeria Rego A.; Reis, Luiza De C.; Ferreira, Paulo Michel Pinheiro; Pessoa, Claudia; Wanderley, Almir Goncalves; Mota, Fernanda Virginia B.; Da Silva, Teresinha G. [Medicinal Chemistry Research, 2014, vol. 23, # 4, p. 1701 - 1708]
[14]Fling et al. [Journal of the American Chemical Society, 1947, vol. 69, p. 2466] Shankman; Schvo [Journal of the American Chemical Society, 1958, vol. 80, p. 1164,1167] Schumann; Boissonnas [Helvetica Chimica Acta, 1952, vol. 35, p. 2237,2240]
[15]Meier, Chris; Boche, Gernot [Chemische Berichte, 1990, vol. 123, # 8, p. 1691 - 1698]
[16]Easton, Christopher J.; Hutton, Craig A.; Tan, Eng Wui; Tiekink, Edward R. T. [Tetrahedron Letters, 1990, vol. 31, # 48, p. 7059 - 7062]
[17]Griesbeck, Axel G.; Nerowski, Frank; Lex, Johann [Journal of Organic Chemistry, 1999, vol. 64, # 14, p. 5213 - 5217]
[18]Skowronek; Gawronski [Tetrahedron Asymmetry, 1999, vol. 10, # 23, p. 4585 - 4590]
[19]Hoshino; Yamamoto [Journal of the American Chemical Society, 2000, vol. 122, # 42, p. 10452 - 10453]
[20]Hill, Roger R.; Birch, David; Jeffs, Graham E.; North, Michael [Organic and Biomolecular Chemistry, 2003, vol. 1, # 6, p. 965 - 972]
[21]Location in patent: scheme or table Al-Farhan, Khalid; Ghazzali, Mohamed; Al-Hazimi, Hassan M.A.; El-Faham, Ayman; Reedijk, Jan [Journal of Molecular Structure, 2011, vol. 994, # 1-3, p. 269 - 275]
[22]Location in patent: scheme or table Mallakpour, Shadpour; Asadi, Parvin; Sabzalian, Mohammad R. [Amino Acids, 2011, vol. 41, # 5, p. 1215 - 1222]
[23]Location in patent: experimental part Hassan, Hammed H.A.M.; El-Banna, Sabah G.; Elhusseiny, Amel F.; Mansour, El-Sayed M.E. [Molecules, 2012, vol. 17, # 7, p. 8255 - 8275]
[24]Gruzdev, Dmitry A.; Levit, Galina L.; Krasnov, Victor P. [Tetrahedron Asymmetry, 2012, vol. 23, # 24, p. 1640 - 1646]
[25]He, Gang; Zhang, Shu-Yu; Nack, William A.; Li, Qiong; Chen, Gong [Angewandte Chemie - International Edition, 2013, vol. 52, # 42, p. 11124 - 11128][Angew. Chem., 2013, vol. 125, # 42, p. 11330 - 11334,5]
[26]Cai, Yan; Lyu, Hairong; Yu, Chengbin; Miao, Zhiwei [Advanced Synthesis and Catalysis, 2014, vol. 356, # 2-3, p. 596 - 602]
[27]Cai, Yan; Ge, Haihong; Sun, Weize; Miao, Zhiwei [Synthesis, 2015, vol. 47, # 11, p. 1669 - 1677]
[28]Current Patent Assignee: SINEVIR THERAPEUTICS - US9181281, 2015, B2 Location in patent: Page/Page column 23; 24
[29]Ge, Haihong; Liu, Shuang; Cai, Yan; Sun, Yuchao; Miao, Zhiwei [Synthesis, 2016, vol. 48, # 3, p. 448 - 454]
[30]Bume, Desta Doro; Pitts, Cody Ross; Jokhai, Rayyan Trebonias; Lectka, Thomas [Tetrahedron, 2016, vol. 72, # 40, p. 6031 - 6036]
[31]Jang, Yun-Suk; Dieckmann, Michael; Cramer, Nicolai [Angewandte Chemie - International Edition, 2017, vol. 56, # 47, p. 15088 - 15092][Angew. Chem., 2017, vol. 129, p. 15284 - 15288,5]
[32]Shipilovskikh, Sergei A.; Vaganov, Vladimir Yu.; Denisova, Elena I.; Rubtsov, Aleksandr E.; Malkov, Andrei V. [Organic Letters, 2018, vol. 20, # 3, p. 728 - 731]
[33]Brauns, Marcus; Cramer, Nicolai [Angewandte Chemie - International Edition, 2019, vol. 58, # 26, p. 8902 - 8906][Angew. Chem., 2019, vol. 131, p. 8994 - 8998,5]
[34]Current Patent Assignee: NANKAI UNIVERSITY - CN109970713, 2019, A Location in patent: Paragraph 0073

2
[ 67-56-1 ]
[ 6306-54-3 ]
[ 124729-87-9 ]

Yield	Reaction Conditions	Operation in experiment
98%	With hydrogenchloride at 10℃;
97%	With hydrogenchloride at 0℃; for 12h;
94%	With hydrogenchloride at 10℃; for 4h;

90%	With thionyl chloride at 0 - 20℃;	(S)-2-(1,3-dioxoisoindolin-2-yl)-3-methylbutanoic acid (L-N-Phthaloylvaline, 27) and methyl (S)-2-(1,3-dioxoisoindolin-2-yl)-3-methylbutanoate (L-N-Phthaloylvaline methyl ester, S6) A mixture of L-leucine (1.17 g, 10.0 mmol) and phthalic anhydride (1.0 equiv, 1.48 g, 10.0mmol) was stirred and heated at 170 °C for 1 h under reduced pressure. Cooling thereaction mixture to rt afforded spectroscopically pure 27 (2.41 g, 9.75 mmol, 97%). 27 wasused for the next step without further purification as follows: to 27 (0.99 g, 4.00 mmol) inMeOH (40mL) was added thionyl chloride (4.0 equiv, 1.90 g, 16.0 mmol) at 0 °C dropwise. The resultingmixture was warmed to rt and stirred overnight. The reaction mixture was concentrated in vacuo, silicagel column chromatography (hexane/EtOAc = 5/1, v/v) gave S6 (0.94 g, 90%) as a colorless liquid. TheNMR data of 27 and S6 were consistent with those previously reported.
81%	With thionyl chloride at 20℃; for 4h;
	With acid

Reference： [1]Griesbeck, Axel G.; Mauder, Harald [Angewandte Chemie, 1992, vol. 104, # 1, p. 97 - 99]
[2]Griesbeck, Axel G.; Hirt, Joachim; Peters, Karl; Peters, Eva-Maria; Schnering, Hans-Georg von [Liebigs Annalen, 1995, # 4, p. 619 - 624]
[3]Griesbeck, Axel G.; Mauder, Harald; Mueller, Ingrid [Chemische Berichte, 1992, vol. 125, # 11, p. 2467 - 2476]
[4]Baran, Phil S.; Chen, Longrui; Chen, Miao; Hoshikawa, Tamaki; Kawamata, Yu; Li, Chao; Mykhailiuk, Pavel; Nakamura, Hugh; Peters, Byron K.; Reisberg, Solomon H.; Shibuguchi, Tomoyuki; Takahira, Yusuke [Synlett, 2019, vol. 30, # 10, p. 1178 - 1182]
[5]Nathanael, Joses G.; Wille, Uta [Journal of Organic Chemistry, 2019, vol. 84, # 6, p. 3405 - 3418]
[6]Easton, Christopher J.; Hutton, Craig A.; Tan, Eng Wui; Tiekink, Edward R. T. [Tetrahedron Letters, 1990, vol. 31, # 48, p. 7059 - 7062]

3
[ 6306-54-3 ]
[ 5511-73-9 ]

Yield	Reaction Conditions	Operation in experiment
94%	With thionyl chloride for 1h; Ambient temperature;
93%	With thionyl chloride for 2.16667h; Reflux;
90%	With thionyl chloride In dichloromethane at 50℃; for 4h;

85%	With thionyl chloride In dichloromethane for 5h; Heating;
85%	With oxalyl dichloride In hexane; N,N-dimethyl-formamide; benzene at 20℃;	1 N-Phthaloyl-(S)-amino acyl chlorides 2b, c, e. General procedure: Oxalyl chloride (1.15 mL, 13.2 mmol) and DMF (5 lL) were added to a suspension of N-phthaloyl-(S)-amino acid (6 mmol) in a hexane-C6H6 1:1 mixture (30 mL). The reaction mixture was stirred at ambient temperature for 5-7 h and then evaporated under reduced pressure. The residue was treated with hexane (40 mL) and the precipitate formed was filtered off and dried in vacuo over P2O5. 4.2.1 N-Phthaloyl-(S)-valyl chloride 2b Colourless solid (1.36 g, 85%): mp 122-123 °C (hexane) (lit. 120-121 °C 18a ; 121-122 °C 18b ). (c 1.0, C6H6) {lit. 18b (c 1.5, C6H6)}. 1H NMR (400 MHz, CDCl3): δ 0.92 (3H, d, J 6.8 Hz, Me-3B); 1.17 (3H, d, J 6.8 Hz, Me-3A); 2.76 (1H, dsept, J 8.4, 6.8 Hz, H-3); 4.75 (1H, d, J 8.4 Hz, H-2); 7.81 (2H, m, Phth); 7.94 (2H, m, Phth). Anal. calcd for C13H12ClNO3 (265.70): C, 58.77; H, 4.55; N, 5.27; Cl, 13.34; found: C, 59.05; H, 4.38; N, 5.25; Cl, 13.06.
	With phosphorus pentachloride In benzene for 1h;
	With phosphorus pentachloride In 1,2-dichloro-ethane 1.) 30 min ,0 deg C, 2.) 16 h, r. t.;
	With thionyl chloride In toluene at 60℃; for 1h; Inert atmosphere;
	With thionyl chloride
	With thionyl chloride In tetrahydrofuran for 2.5h; Inert atmosphere; Reflux;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; Inert atmosphere;
	With thionyl chloride In dichloromethane
	With thionyl chloride In tetrahydrofuran at 20℃;
	With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 1h;
	With thionyl chloride In toluene Reflux; Schlenk technique;
	With thionyl chloride at 60℃; for 1h;	General procedure for the coupling of homophthalic acid 7 with 5a-d General procedure: A mixture of (2S)-N protected carboxylic acids 3a-d (1mmol, 1equiv) and SOCl2 (1.1mmol, 1.1equiv) was heated at 60°C for 1h under dry conditions to afford acid chlorides 5a-c. Homophthalic acid 7 (0.25mmol, 0.25equiv) was added and the reaction mixture was heated at 200°C for 6h. The crude product was poured into chilled water (20mL) and partitioned with EtOAc (3×25mL). The organic phase was dried over anhydrous Na2SO4, the mixture was filtered, and the solvent was removed under reduced pressure. The residue was subjected to column chromatography with EtOAc and n-hexane as the mobile phase to give crystals of 9a-c, 10 and 11.
	With thionyl chloride; N,N-dimethyl-formamide at 90℃; for 2h;	2.4 (S)-2-(1-(4-Benzylpiperidin-1-yl)-4-methyl-1-oxopentan-2-yl)isoindoline-1,3-dione (13) General procedure: N-phthaloyl-l-leucine, 1 (1 g, 3.83 mmol), DMF (0.05 mL, 0.65 mmol) and freshly distilled thionyl chloride (0.5 mL, slow addition) were mixed together and the contents were heated at 90 °C for 2 h. The reaction mixture was cooled to room temperature and kept in an ice bath. 4-Benzylpiperidine (1.0 mL, 5.7 mmol, dissolved in 20 mL of ethylacetate) and triethylamine (1.0 mL) were added subsequently to the reaction mixture and the contents were stirred at room temperature for 2 h. The reaction mixture was concentrated under reduced pressure and extracted into ethylacetate. The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue thus obtained was purified by silica gel chromatography (9:1-6:4 petroleum ether/ethylacetate gradient) to afford the title compound (1.1 g, 2.6 mmol, 69%). Mp: 78-80 °C; [α]D25 -12.4; 1H NMR (400 MHz, CDCl3): δ 7.77-7.64 (m, 4H, Ar-H), 7.19-6.99 (m, 5H, Ar-H), 5.08 (m, 1H, NCH), 4.46 (m, 1H, benzylic CH2), 3.70 (m, 1H, benzylic CH2), 3.0 (m, 1H, CH2), 2.58-2.42 (m, 4H, 2 * NCH2), 1.69-1.46 (m, 6H), 1.18-1.04 (m, 1H, CH), 0.87 (d, 6H, J = 4.12 Hz, 2 * CH3), 13C NMR (100 MHz, CDCl3): δ 168.3 (C=O), 167.6 (C=O), 139.8 (Ar-C), 134.0 (Ar-C), 131.7 (Ar-C), 128.9 (Ar-C), 128.2 (Ar-C), 126.0 (Ar-C), 123.3 (Ar-C), 50.3 (CH), 42.7 (CH2), 31.7 (CH2), 25.3 (CH), 23.1 (CH3), 21.1 (CH3); IR (KBr) νmax (cm-1) = 3025, 2930, 2869, 1715 (C=O), 1655 (C=O), 1448, 1381, 1076, 720; HRMS m/z calculated [M+H]+ for C26H31N2O3+: 419.2329; found: 419.1951.
	With thionyl chloride In toluene Schlenk technique; Reflux;
	With thionyl chloride In neat (no solvent) at 60℃; for 1h;
	With oxalyl dichloride In dichloromethane for 0.5h; Reflux;	15 Oxalyl chloride is added to solution of E in DCM. After refluxing for 30 minutes, the volatile components are evaporated and the residue is purified by recrystallization from DMC and hexane under argon environment. The product (F) is dried overnight under high vacuum before it can react with aldehyde by catalyzing with ZnCl2 in DCM at 0 degree C. At the end of reaction, the reaction mixture is passed through a plug of Al2O3 to obtain product G with purity at 95%. No further purification is necessary.
	With thionyl chloride In toluene Reflux; Schlenk technique; Inert atmosphere;
	With chlorinating agent
	With thionyl chloride In dichloromethane for 4h; Reflux;
	With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 0℃;
	With thionyl chloride In tetrahydrofuran at 20℃; for 16h;	A A. (S)-2-(1,3-dioxoisoindolin-2-yl)-3-methylbutanoyl chloride Thionyl chloride (3.12 mL, 42.8 mmol) was added to (S)-2-(1 ,3-dioxoisoindolin-2-yl)-3- methylbutanoic acid (10.57 g, 42.8 mmol) in tetrahydrofuran (214 mL) at room temperature and the reaction mixture was stirred for sixteen hours, then concentrated to give crude (S)-2-(1 ,3- dioxoisoindolin-2-yl)-3-methylbutanoyl chloride (1 1 .36 g, 40.6 mmol, 95 % yield), which was carried forward into the next reaction.
	With thionyl chloride In tetrahydrofuran at 20℃; for 16h;	A. (S)-2-(1 ,3-Dioxoisoindolin-2-yl)-3-methylbutanoyl chloride Thionyl chloride (3.12 mL, 42.8 mmol) was added to (S)-2-(1 ,3-dioxoisoindolin-2- yl)-3-methylbutanoic acid (10.57 g, 42.8 mmol) in tetrahydrofuran (214 mL) at room temperature and the reaction mixture was stirred for sixteen hours, then concentrated to give crude (S)-2-(1 ,3-dioxoisoindolin-2-yl)-3-methylbutanoyl chloride (11 .36 g, 40.6 mmol, 95 % yield), which was carried forward into the next reaction.
	With oxalyl dichloride; N,N-dimethyl-formamide In hexane; benzene for 4h;	3.2 Step 2 To a solution of (S)-2-(l,3-dioxoisoindolin-2-yl)-3-methylbutanoic acid (5.0 g, 20 mmol) in a mixture of hexane/benzene (40 mL/40 mL) was added oxalyl chloride (3.5 mL, 40 mmol) in a dropwise manner, followed by DMF (0.02 mL). After 4 hrs, all volatiles were completely removed via rotovap. The resulting (S)-2-(l,3-dioxoisoindolin-2-yl)-3-methylbutanoyl chloride as a crude was used in next step without further purification.
	With thionyl chloride In dichloromethane Reflux;

Reference： [1]Aitken, R. Alan; Cooper, Harris R.; Mehrotra, Amit P. [Journal of the Chemical Society. Perkin transactions I, 1996, # 5, p. 475 - 483]
[2]Location in patent: experimental part Hassan, Hammed H.A.M.; El-Banna, Sabah G.; Elhusseiny, Amel F.; Mansour, El-Sayed M.E. [Molecules, 2012, vol. 17, # 7, p. 8255 - 8275]
[3]Juaristi; Beck; Hansen; Matt; Mukhopadhyay; Simson; Seebach [Synthesis, 1993, # 12, p. 1271 - 1290]
[4]Mizrahi, Dana M.; Waner, Trevor; Segall, Yoffi [Phosphorus, Sulfur and Silicon and the Related Elements, 2001, vol. 173, p. 1 - 25]
[5]Gruzdev, Dmitry A.; Levit, Galina L.; Krasnov, Victor P. [Tetrahedron Asymmetry, 2012, vol. 23, # 24, p. 1640 - 1646]
[6]Meier, Chris; Boche, Gernot [Chemische Berichte, 1990, vol. 123, # 8, p. 1691 - 1698]
[7]Effenberger, Franz; Steegmueller, Dieter [Chemische Berichte, 1988, vol. 121, p. 117 - 124]
[8]Hermange, Philippe; Dau, Marie Elise Tran Huu; Retailleau, Pascal; Dodd, Robert H. [Organic Letters, 2009, vol. 11, # 18, p. 4044 - 4047]
[9]Location in patent: scheme or table Foroughifar, Naser; Mobinikhaledi, Akbar; Ebrahimi, Sattar [Turkish Journal of Chemistry, 2010, vol. 34, # 4, p. 603 - 611]
[10]Wixey, James S.; Ward, Benjamin D. [Chemical Communications, 2011, vol. 47, # 19, p. 5449 - 5451]
[11]Donohoe, Timothy J.; Callens, Cedric K. A.; Flores, Aida; Mesch, Stefanie; Poole, Darren L.; Roslan, Ishmael A. [Angewandte Chemie - International Edition, 2011, vol. 50, # 46, p. 10957 - 10960]
[12]Location in patent: scheme or table Mallakpour, Shadpour; Asadi, Parvin; Sabzalian, Mohammad R. [Amino Acids, 2011, vol. 41, # 5, p. 1215 - 1222]
[13]He, Gang; Zhang, Shu-Yu; Nack, William A.; Li, Qiong; Chen, Gong [Angewandte Chemie - International Edition, 2013, vol. 52, # 42, p. 11124 - 11128][Angew. Chem., 2013, vol. 125, # 42, p. 11330 - 11334,5]
[14]Nair, Roshna V.; Kotmale, Amol S.; Dhokale, Snehal A.; Gawade, Rupesh L.; Puranik, Vedavadi G.; Rajamohanan, Pattuparambil R.; Sanjayan, Gangadhar J. [Organic and Biomolecular Chemistry, 2014, vol. 12, # 5, p. 774 - 782]
[15]Cai, Yan; Lyu, Hairong; Yu, Chengbin; Miao, Zhiwei [Advanced Synthesis and Catalysis, 2014, vol. 356, # 2-3, p. 596 - 602]
[16]Saddiqa, Aisha; Raza, Abdul R.; Black, David Stc.; Kumar, Naresh [Tetrahedron Asymmetry, 2014, vol. 25, # 9, p. 736 - 743]
[17]Singh, Anil K.; Rajendran, Vinoth; Pant, Akansha; Ghosh, Prahlad C.; Singh, Neelu; Latha; Garg, Sandeep; Pandey, Kailash C.; Singh, Brajendra K.; Rathi, Brijesh [Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 8, p. 1817 - 1827]
[18]Cai, Yan; Ge, Haihong; Sun, Weize; Miao, Zhiwei [Synthesis, 2015, vol. 47, # 11, p. 1669 - 1677]
[19]Raza, Abdul Rauf; Saddiqa, Aisha; Çakmak, Osman [Chirality, 2015, vol. 27, # 12, p. 951 - 957]
[20]Current Patent Assignee: SINEVIR THERAPEUTICS - US9181281, 2015, B2 Location in patent: Page/Page column 23; 24
[21]Ge, Haihong; Liu, Shuang; Cai, Yan; Sun, Yuchao; Miao, Zhiwei [Synthesis, 2016, vol. 48, # 3, p. 448 - 454]
[22]Dey, Aniruddha; Pimparkar, Sandeep; Deb, Arghya; Guin, Srimanta; Maiti, Debabrata [Advanced Synthesis and Catalysis, 2017, vol. 359, # 8, p. 1301 - 1307]
[23]Pati, Tanmay K.; Debnath, Sudipto; Kundu, Mrinalkanti; Khamrai, Uttam; Maiti, Dilip K. [Organic Letters, 2018, vol. 20, # 13, p. 4062 - 4066]
[24]Na, Christina G.; Alexanian, Erik J. [Angewandte Chemie - International Edition, 2018, vol. 57, # 40, p. 13106 - 13109][Angew. Chem., 2018, vol. 130, # 40, p. 13290 - 13293,4]
[25]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2018/229629, 2018, A1 Location in patent: Page/Page column 91
[26]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2020/95215, 2020, A1 Location in patent: Page/Page column 63-64
[27]Current Patent Assignee: THE ROSKAMP INST - WO2020/154420, 2020, A2 Location in patent: Page/Page column 33
[28]Tukhtaev; Yusupov; Vinogradova [Egyptian Journal of Chemistry, 2021, vol. 64, # 6, p. 3049 - 3058]

4
[ 72-18-4 ]
[ 22509-74-6 ]
[ 6306-54-3 ]

Yield	Reaction Conditions	Operation in experiment
71%	With sodium carbonate In ethyl acetate
	Stage #1: L-valine; N-ethoxycarbonylphthalimide With sodium carbonate In water at 20℃; for 3h; Stage #2: With hydrogenchloride In water at 0℃;
	With sodium carbonate In water at 20℃; for 16h;

With sodium carbonate In water at 20℃; for 5h;

Reference： [1]Aitken, R. Alan; Cooper, Harris R.; Mehrotra, Amit P. [Journal of the Chemical Society. Perkin transactions I, 1996, # 5, p. 475 - 483]
[2]Dey, Aniruddha; Pimparkar, Sandeep; Deb, Arghya; Guin, Srimanta; Maiti, Debabrata [Advanced Synthesis and Catalysis, 2017, vol. 359, # 8, p. 1301 - 1307]
[3]Pati, Tanmay K.; Debnath, Sudipto; Kundu, Mrinalkanti; Khamrai, Uttam; Maiti, Dilip K. [Organic Letters, 2018, vol. 20, # 13, p. 4062 - 4066]
[4]Chen, Zhongxiang; Fan, Hongjun; Yang, Shiwei; Bian, Guangling; Song, Ling [Organic and Biomolecular Chemistry, 2018, vol. 16, # 37, p. 6933 - 6939]

5
[ 112450-34-7 ]
[ 6306-54-3 ]
(S)-2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-methyl-thiobutyric acid S-(4-cyano-5,6-diphenyl-pyridazin-3-yl) ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With dicyclohexyl-carbodiimide In tetrahydrofuran at 0 - 20℃; for 48h;

Reference： [1]Ibrahim, T.M.; Donia, S.G.; Magdel-Din, A.A. [Egyptian Journal of Chemistry, 1994, vol. 37, # 3, p. 273 - 282]

6
[ 79225-55-1 ]
[ 6306-54-3 ]
(S)-2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-methyl-butyric acid 4-cyano-5,6-diphenyl-pyridazin-3-yl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With dicyclohexyl-carbodiimide In tetrahydrofuran at 0 - 20℃; for 48h;

Reference： [1]Ibrahim, T.M.; Donia, S.G.; Magdel-Din, A.A. [Egyptian Journal of Chemistry, 1994, vol. 37, # 3, p. 273 - 282]

7
3-Hydroxy-5,6-diphenyl-pyridazine-4-carboxylic acid [ No CAS ]
[ 6306-54-3 ]
3-[(S)-2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-methyl-butyryloxy]-5,6-diphenyl-pyridazine-4-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With dicyclohexyl-carbodiimide In tetrahydrofuran at 0 - 20℃; for 48h;

Reference： [1]Ibrahim, T.M.; Donia, S.G.; Magdel-Din, A.A. [Egyptian Journal of Chemistry, 1994, vol. 37, # 3, p. 273 - 282]

8
[ 128627-93-0 ]
[ 6306-54-3 ]
3-[(S)-2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-methyl-butyrylsulfanyl]-5,6-diphenyl-pyridazine-4-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With dicyclohexyl-carbodiimide In tetrahydrofuran at 0 - 20℃; for 48h;

Reference： [1]Ibrahim, T.M.; Donia, S.G.; Magdel-Din, A.A. [Egyptian Journal of Chemistry, 1994, vol. 37, # 3, p. 273 - 282]

9
[ 6973-51-9 ]
[ 6306-54-3 ]
(S)-2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-methyl-N-(4-nitro-benzothiazol-2-yl)-butyramide [ No CAS ]

Reference： [1]Pakistan Journal of Scientific and Industrial Research,1995,vol. 38,p. 246 - 248

10
[ 213532-60-6 ]
[ 6306-54-3 ]
S-[(1'S,2'R)-10'-(diisopropylsulfamoyl)isobornyl] (2S)-3-methyl-2-phthalimidobutanethioate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
28%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 0 - 20℃; for 5h;

Reference： [1]Barrett, Anthony G. M.; Braddock, D. Christopher; Christian, Paul W. N.; Pilipauskas, Daniel; White, Andrew J. P.; Williams, David J. [Journal of Organic Chemistry, 1998, vol. 63, # 17, p. 5818 - 5823]

11
[ 78277-26-6 ]
[ 6306-54-3 ]
6-[(S)-2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-3-methyl-butyryloxy]-hexanoic acid benzyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With potassium carbonate In N,N-dimethyl-formamide for 16h; Ambient temperature;

Reference： [1]Griesbeck, Axel G.; Nerowski, Frank; Lex, Johann [Journal of Organic Chemistry, 1999, vol. 64, # 14, p. 5213 - 5217]

12
L-valine hydrochloride [ No CAS ]
[ 438470-19-0 ]
[ 6306-54-3 ]

Yield	Reaction Conditions	Operation in experiment
89%	With potassium carbonate In acetonitrile at 20℃; for 3h;

Reference： [1]Casimir, J Richard; Guichard, Gilles; Briand, Jean-Paul [Journal of Organic Chemistry, 2002, vol. 67, # 11, p. 3764 - 3768]

13
[ 560110-12-5 ]
[ 6306-54-3 ]
Phth-L-Val-D-Val-NHMe [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With benzotriazol-1-ol; triethylamine; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 24h;

Reference： [1]Hill, Roger R.; Birch, David; Jeffs, Graham E.; North, Michael [Organic and Biomolecular Chemistry, 2003, vol. 1, # 6, p. 965 - 972]

14
[ 124491-96-9 ]
[ 6306-54-3 ]
(S)-N-((R)-1-Dimethylcarbamoyl-ethyl)-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-methyl-butyramide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With benzotriazol-1-ol; triethylamine; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 24h;

Reference： [1]Hill, Roger R.; Birch, David; Jeffs, Graham E.; North, Michael [Organic and Biomolecular Chemistry, 2003, vol. 1, # 6, p. 965 - 972]

15
[ 3705-50-8 ]
[ 6306-54-3 ]
(S)-N-((R)-1-Dimethylcarbamoyl-2-phenyl-ethyl)-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-methyl-butyramide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With benzotriazol-1-ol; triethylamine; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 24h;

Reference： [1]Hill, Roger R.; Birch, David; Jeffs, Graham E.; North, Michael [Organic and Biomolecular Chemistry, 2003, vol. 1, # 6, p. 965 - 972]

16
[ 230643-41-1 ]
[ 6306-54-3 ]
(S)-N-((R)-1-Dimethylcarbamoyl-2-methyl-propyl)-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-methyl-butyramide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With benzotriazol-1-ol; triethylamine; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 24h;

Reference： [1]Hill, Roger R.; Birch, David; Jeffs, Graham E.; North, Michael [Organic and Biomolecular Chemistry, 2003, vol. 1, # 6, p. 965 - 972]

17
[ 6306-54-3 ]
[ 667466-72-0 ]
[ 667466-92-4 ]

Yield	Reaction Conditions	Operation in experiment
71%	With dicyclohexyl-carbodiimide In tetrahydrofuran at 0 - 20℃; for 17h;
71%	With dicyclohexyl-carbodiimide In tetrahydrofuran at 0 - 20℃; for 17h;

Reference： [1]Aly; Wasfy [Phosphorus, Sulfur and Silicon and the Related Elements, 2003, vol. 178, # 9, p. 1911 - 1921]
[2]Aly; Wasfy [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2004, vol. 43, # 3, p. 629 - 635]

18
[ 6306-54-3 ]
[ 667466-69-5 ]
[ 667466-76-4 ]

Yield	Reaction Conditions	Operation in experiment
58%	With dicyclohexyl-carbodiimide In tetrahydrofuran at 0 - 20℃; for 17h;
58%	With dicyclohexyl-carbodiimide In tetrahydrofuran at 0 - 20℃; for 17h;

Reference： [1]Aly; Wasfy [Phosphorus, Sulfur and Silicon and the Related Elements, 2003, vol. 178, # 9, p. 1911 - 1921]
[2]Aly; Wasfy [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2004, vol. 43, # 3, p. 629 - 635]

19
[ 6306-54-3 ]
[ 667466-71-9 ]
[ 667466-84-4 ]

Yield	Reaction Conditions	Operation in experiment
66%	With dicyclohexyl-carbodiimide In tetrahydrofuran at 0 - 20℃; for 17h;

Reference： [1]Aly; Wasfy [Phosphorus, Sulfur and Silicon and the Related Elements, 2003, vol. 178, # 9, p. 1911 - 1921]

20
[ 74-89-5 ]
[ 6306-54-3 ]
[ 512827-74-6 ]

Yield	Reaction Conditions	Operation in experiment
98%	With 4-methyl-morpholine; isobutyl chloroformate In tetrahydrofuran; water at -20℃; for 1h;

Reference： [1]Shendage, Deepak M.; Froehlich, Roland; Haufe, Guenter [Organic Letters, 2004, vol. 6, # 21, p. 3675 - 3678]

21
[ 6306-54-3 ]
[ 667466-71-9 ]
[ 667466-84-4 ]

Yield	Reaction Conditions	Operation in experiment
66%	With dicyclohexyl-carbodiimide In tetrahydrofuran at 0 - 20℃; for 17h;

Reference： [1]Aly; Wasfy [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2004, vol. 43, # 3, p. 629 - 635]

22
[ 6306-54-3 ]
[ 828253-37-8 ]
2-{(S)-1-[(4R,6R)-6-((R)-5,5-Dimethyl-2-oxo-tetrahydro-furan-3-yloxy)-2-oxo-4-phenyl-[1,3]oxazinane-3-carbonyl]-2-methyl-propyl}-isoindole-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In acetonitrile at 20℃; for 16h;

Reference： [1]Yin, Biaolin; Dhal, Robert; Maisonneuve, Vincent; Dujardin, Gilles [European Journal of Organic Chemistry, 2006, # 15, p. 3309 - 3313]

23
[ 6306-54-3 ]
[ 2624-36-4 ]

Yield	Reaction Conditions	Operation in experiment
48%	Stage #1: N-phthaloyl L-valine With chloroformic acid ethyl ester; triethylamine In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: With ammonia In tetrahydrofuran; water at 0℃; for 0.5h; Inert atmosphere;
	Multi-step reaction with 2 steps 1: Et₃N / 0.25 h / 0 °C 2: aq. NH₃ / 0.08 h / 0 °C
	Multi-step reaction with 4 steps 1: N-ethyl-N,N-diisopropylamine; benzotriazol-1-ol; dmap; dicyclohexyl-carbodiimide / N,N-dimethyl-formamide / 18 h / 20 °C 2: triethylamine / dichloromethane / 0 - 20 °C 3: triethylamine / dichloromethane / 4 h / Reflux 4: pyridinium polyhydrogenfluoride; N-Bromosuccinimide / dichloromethane / 18 h / 20 °C

2.09 g

Stage #1: N-phthaloyl L-valine With thionyl chloride Stage #2: With ammonium hydroxide

Reference： [1]Location in patent: experimental part Cam, Thuy Hoang; Bouillere, Francelin; Johannesen, Sine; Zulauf, Anais; Panel, Cecilia; Pouilhes, Annie; Gori, Didier; Alezra, Valerie; Kouklovsky, Cyrille [Journal of Organic Chemistry, 2009, vol. 74, # 11, p. 4177 - 4187]
[2]Bagley, Mark C.; Buck, Richard T.; Hind, S. Lucy; Moody, Christopher J. [Journal of the Chemical Society. Perkin transactions I, 1998, # 3, p. 591 - 600]
[3]Ulbrich, Dirk; Daniliuc, Constantin G.; Haufe, Günter [Journal of Fluorine Chemistry, 2016, vol. 188, p. 65 - 75]
[4]Shipilovskikh, Sergei A.; Vaganov, Vladimir Yu.; Denisova, Elena I.; Rubtsov, Aleksandr E.; Malkov, Andrei V. [Organic Letters, 2018, vol. 20, # 3, p. 728 - 731]

24
[ 6306-54-3 ]
[ 20556-14-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: dicyclohexylcarbodiimide; tetrahydrofuran / Behandeln des Reaktionsprodukts mit wss.Natronlauge in Dioxan 2: N₂H₄+H₂O; ethanol

Reference： [1]Obata; Mizutani [Journal of the Agricultural Chemical Society of Japan, 1959, vol. 23, p. 121,123]

25
[ 6306-54-3 ]
[ 3918-94-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: dicyclohexylcarbodiimide / Erwaermen des Reaktionsprodukts mit wss.Salzsaeure in Aceton 2: N₂H₄+H₂O; ethanol

Reference： [1]Shankman; Schvo [Journal of the American Chemical Society, 1958, vol. 80, p. 1164,1167]

26
[ 40204-26-0 ]
[ 6306-54-3 ]
[ 1094530-70-7 ]

Yield	Reaction Conditions	Operation in experiment
55%	Stage #1: N-phthaloyl L-valine With 1,1'-carbonyldiimidazole In tetrahydrofuran Inert atmosphere; Stage #2: malonic acid monobenzyl ester With dibutylmagnesium In tetrahydrofuran; n-heptane at 0℃; Inert atmosphere; Stage #3: In tetrahydrofuran; n-heptane for 0.5h; Inert atmosphere;

Reference： [1]Lin, Weimin; Theberge, Cory R.; Henderson, Timothy J.; Zercher, Charles K.; Jasinski, Jerry; Butcher, Ray J. [Journal of Organic Chemistry, 2009, vol. 74, # 2, p. 645 - 651]

27
[ 72-18-4 ]
[ 88-95-9 ]
[ 6306-54-3 ]

Yield	Reaction Conditions	Operation in experiment
70%	With triethylamine In dichloromethane at 20℃; Inert atmosphere;

Reference： [1]Location in patent: scheme or table Cam, Thuy Hoang; Bouillere, Francelin; Johannesen, Sine; Zulauf, Anais; Panel, Cecilia; Pouilhes, Annie; Gori, Didier; Alezra, Valerie; Kouklovsky, Cyrille [Journal of Organic Chemistry, 2009, vol. 74, # 11, p. 4177 - 4187]

28
[ 1417710-91-8 ]
[ 6306-54-3 ]
[ 1417710-94-1 ]

Yield	Reaction Conditions	Operation in experiment
90%	With trichlorophosphate for 16h; Reflux;	Experimental General procedure: A mixture of amino triazole 1a-b (2 mmol), N-phethaloyl-l-amino acid 2a-d (2 mmol) in POCl3 (10 mL) was refluxed for 16 h. The reaction mixture slowly was poured into crashed ice with stirring and neutralized with solid potassium carbonate. The mixture was allowed to stand overnight and the solid separated out was filtered and washed with cold water. The compound so obtained was dried and giving the pure products 3a-h.

Reference： [1]Ebrahimi, Sattar; Sayadi, Masoomeh; Darvishi, Ghasem [Chinese Chemical Letters, 2012, vol. 23, # 12, p. 1335 - 1338]

29
[ 4413-43-8 ]
[ 6306-54-3 ]
[ 1417710-98-5 ]

Yield	Reaction Conditions	Operation in experiment
90%	With trichlorophosphate for 16h; Reflux;	Experimental General procedure: A mixture of amino triazole 1a-b (2 mmol), N-phethaloyl-l-amino acid 2a-d (2 mmol) in POCl3 (10 mL) was refluxed for 16 h. The reaction mixture slowly was poured into crashed ice with stirring and neutralized with solid potassium carbonate. The mixture was allowed to stand overnight and the solid separated out was filtered and washed with cold water. The compound so obtained was dried and giving the pure products 3a-h.

Reference： [1]Ebrahimi, Sattar; Sayadi, Masoomeh; Darvishi, Ghasem [Chinese Chemical Letters, 2012, vol. 23, # 12, p. 1335 - 1338]

30
[ 123-75-1 ]
[ 6306-54-3 ]
[ 1605299-98-6 ]

Yield	Reaction Conditions	Operation in experiment
77%	Stage #1: N-phthaloyl L-valine With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0℃; Stage #2: With benzotriazol-1-ol In dichloromethane at 0℃; Stage #3: pyrrolidine In dichloromethane at 0 - 20℃; for 24h;

Reference： [1]Singh, Anil K.; Kishan, Ram; Bahadur, Vijay; Vijayan, Narayanasamy; Balachandran, Vadivelu; Tiwari, Hemandra K.; Singh, Brajendra K.; Rathi, Brijesh [Journal of Physical Organic Chemistry, 2014, vol. 27, # 6, p. 490 - 497]

31
[ 110-89-4 ]
[ 6306-54-3 ]
[ 1605299-99-7 ]

Yield	Reaction Conditions	Operation in experiment
79%	Stage #1: N-phthaloyl L-valine With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0℃; Stage #2: With benzotriazol-1-ol In dichloromethane at 0℃; Stage #3: piperidine In dichloromethane at 0 - 20℃; for 24h;

Reference： [1]Singh, Anil K.; Kishan, Ram; Bahadur, Vijay; Vijayan, Narayanasamy; Balachandran, Vadivelu; Tiwari, Hemandra K.; Singh, Brajendra K.; Rathi, Brijesh [Journal of Physical Organic Chemistry, 2014, vol. 27, # 6, p. 490 - 497]

32
[ 110-91-8 ]
[ 6306-54-3 ]
[ 154462-94-9 ]

Yield	Reaction Conditions	Operation in experiment
82%	Stage #1: N-phthaloyl L-valine With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0℃; Stage #2: With benzotriazol-1-ol In dichloromethane at 0℃; Stage #3: morpholine In dichloromethane at 0 - 20℃; for 24h;

Reference： [1]Singh, Anil K.; Kishan, Ram; Bahadur, Vijay; Vijayan, Narayanasamy; Balachandran, Vadivelu; Tiwari, Hemandra K.; Singh, Brajendra K.; Rathi, Brijesh [Journal of Physical Organic Chemistry, 2014, vol. 27, # 6, p. 490 - 497]

33
[ 1415097-58-3 ]
[ 6306-54-3 ]
N-phthaloyl-L-valinyl-N-acetylglycine methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With silver carbonate In dichloromethane at 20℃; for 2h;

Reference： [1]Pourvali, Aysa; Cochrane, James R.; Hutton, Craig A. [Chemical Communications, 2014, vol. 50, # 100, p. 15963 - 15966]

34
[ 116287-43-5 ]
[ 6306-54-3 ]
N-phthaloyl-L-valinyl-N-acetyl-L-alanine methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With silver carbonate In dichloromethane at 20℃; for 2h;

Reference： [1]Pourvali, Aysa; Cochrane, James R.; Hutton, Craig A. [Chemical Communications, 2014, vol. 50, # 100, p. 15963 - 15966]

35
[ 105740-12-3 ]
[ 6306-54-3 ]
N-phthaloyl-L-valinyl-N-acetyl-L-valine methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With silver carbonate In dichloromethane at 20℃; for 2h;

Reference： [1]Pourvali, Aysa; Cochrane, James R.; Hutton, Craig A. [Chemical Communications, 2014, vol. 50, # 100, p. 15963 - 15966]

36
N-thioacetyl-L-leucine methyl ester [ No CAS ]
[ 6306-54-3 ]
N-phthaloyl-L-valinyl-N-acetyl-L-leucine methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	With silver carbonate In dichloromethane at 20℃; for 2h;

Reference： [1]Pourvali, Aysa; Cochrane, James R.; Hutton, Craig A. [Chemical Communications, 2014, vol. 50, # 100, p. 15963 - 15966]

37
(2S,3S)-1,4-bis(phenylmethoxy)-2,3-diaminobutane [ No CAS ]
[ 6306-54-3 ]
(2S,2'S)-N,N'-((2S,3S)-1,4-bis(benzyloxy)butane-2,3-diyl)bis(2-(1,3-dioxoisoindolin-2-yl)-3-methylbutanamide) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	Stage #1: N-phthaloyl L-valine With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 15h; Inert atmosphere; Stage #2: (2S,3S)-1,4-bis(phenylmethoxy)-2,3-diaminobutane In dichloromethane Inert atmosphere;	Preparation of (2S,2'S)-N,N'-((2S,3S)-1,4-bis(benzyloxy)butane-2,3-diyl)bis(2-(1,3-dioxoisoindolin-2-yl)-3-methylbutanamide) L4 2.75g (7.2 mmol) of HBTU was added to a stirred solution of 1.8g (7.2 mmol) of phthalimideprotected (L)- valine and DIPEA (2.5 mL, 14.4 mmol) in dry DCM (21 mL) at 0 °C under argonatm; the resulting mixture was stirred another 15 min followed by 1g (3.33 mmol) of (2S,3S)-1,4-bis(benzyloxy)butane-2,3-diamine was added and the stirring continued until reactioncomplete (monitored by TLC). The reaction mixture was quenched by addition of H2O followedby diluted with DCM (40 mL). The organic phase was washed successively with 10% aqueousNOBocOMeClS4HCl solution, saturated aqueous NaHCO3 and brain solution. Then the fractions were dried byanhydrous Na2SO4 concentrated through Rotaryevaporator. The residue was purified over columnchromatography (100-200 mesh silica gel, 30% ethylacetate-hexane). After column purification 1.97g(2.6mmol, 78% yield) of the desired bis-amide wasisolated as foamy solid. 1H NMR (500 MHz, CDCl3): δ7.83-7.81(m, 2H), 7.73-7.71(m, 2H), 7.35-7.31(m, 1H), 7.27-7.21(m, 5H), 4.42-4.34(m, 4H),3.55-3.47(m, 2H), 2.78-2.73(m, 1H), 1.04(d, J = 6.5 Hz, 3H), (d, J = 6.5 Hz, 3H), 0.84(d, J =6.5 Hz, 3H). 13C NMR (125 MHz, CDCl3): 168.7, 168.2, 137.6, 134.1, 131.5, 128.3, 127.7,127.6, 127.5, 123.5, 73.2, 69.2, 62.0, 50.5, 27.5, 20.3, 19.4. IR (ν, cm-1): 3340, 2984, 1720, 1685,1512, 1464, 1350, 1062, 1013, 823.1 equivalent of O-Bn bisamide was

Reference： [1]Jayakumar, Samydurai; Kumarswamyreddy, Nandarapu; Prakash, Muthuraj; Kesavan, Venkitasamy [Organic Letters, 2015, vol. 17, # 5, p. 1066 - 1069]

38
C₁₅H₂₅N₃O [ No CAS ]
[ 6306-54-3 ]
C₂₈H₃₆N₄O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: N-phthaloyl L-valine With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0℃; for 1h; Stage #2: C₁₅H₂₅N₃O In dichloromethane at 0 - 20℃; for 24.5h;	General procedure for deprotection and coupling reaction with N-phthaloyl-L-aminoacids to afford 6a-6u. General procedure: A solution of Boc-protected hydroxyethylamines, 5a (101 mg, 0.28mmol) in 5 mL of dichloromethane and 1 mL of trifluoroacetic acid (TFA) was stirred at room temperature for 3 h. The solvent was evaporated under reduced pressure and the oily substance obtained was used for further reactions without purification. In another round bottomed flask, N-phthaloyl-L-leucine (88 mg, 0.34 mmol) in dichloromethane (20 mL) along with triethylamine (TEA) (1 mL), N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDCHCl) (97 mg, 0.51 mmol) and anhydrous 1-hydroxybenzotriazole (HOBt) (69 mg, 0.51mmol) were stirred at 0°C for 1 h followed by addition of Boc-deprotected hydroxyethylamine diluted with dichloromethane (3 mL). This procedure was followed to prepare compounds 6aq. The reaction mixture was stirred at 0°C for another 30 minutes and then at room temperature for 24 h. The reaction mixture was concentrated under reduced pressure. The semi-solid material obtained was diluted with 25 mL of ethyl acetate and washed three times with distilled water. The organic layer obtained was dried over anhydrous Na2SO4 and solvent was evaporated under reduced pressure. The obtained compounds were purified by column chromatography using silica gel as stationary phase and chloroform-methanol (96:4) as eluent that afforded a white solid (6a-q) in fair to good yield (Table 2). The spectroscopic details are furnished in supporting information.To obtain 6r, 6t and 6u, a solution of Boc-protected bis-hydroxyethylpiperazine, 5f (171mg, 0.28 mmol) in 5 mL of dichloromethane and 1 mL of trifluoroacetic acid (TFA) was stirred at room temperature for 3 h. The solvent was evaporated under reduced pressure and the oily substance obtained was used for further reactions without purification. In another round bottomed flask, N-phthaloyl-L-amino acid (161 mg, 0.62 mmol) in dichloromethane (20 mL) along with triethylamine (TEA) (1 mL), N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC•HCl) (177 mg, 0.93 mmol) and anhydrous 1-hydroxybenzotriazole (HOBt) (125 mg, 0.93 mmol) were stirred at 0°C for 1 h followed by addition of Boc-deprotected hydroxyethyl piperazine diluted with dichloromethane (3 mL). The reaction mixture was stirred at 0°C for another 30 minutes and then at room temperature for 24 h. The reaction mixture was concentrated under reduced pressure. The semi-solid material obtained was diluted with 25 mL of ethyl acetate and washed three times with distilled water. The organic layer obtained was dried over anhydrous Na2SO4 and solvent was evaporated under reduced pressure. The obtained compounds were purified by column chromatography using silica gel as stationary phase and chloroform-methanol (96:4) as eluent that afforded a white solid (6r-u) in fair to good yield (Table 3). The spectroscopic details are furnished in supporting information. Compound 6s was prepared following literature procedure [30].

Reference： [1]Singh, Anil K.; Rathore, Sumit; Tang, Yan; Goldfarb, Nathan E.; Dunn, Ben M.; Rajendran, Vinoth; Ghosh, Prahlad C.; Singh, Neelu; Latha; Singh, Brajendra K.; Rawat, Manmeet; Rathi, Brijesh [PLoS ONE, 2015, vol. 10, # 10]

39
C₁₆H₂₇N₃O [ No CAS ]
[ 6306-54-3 ]
C₂₉H₃₈N₄O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: N-phthaloyl L-valine With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0℃; for 1h; Stage #2: C₁₆H₂₇N₃O In dichloromethane at 0 - 20℃; for 24.5h;	General procedure for deprotection and coupling reaction with N-phthaloyl-L-aminoacids to afford 6a-6u. General procedure: A solution of Boc-protected hydroxyethylamines, 5a (101 mg, 0.28mmol) in 5 mL of dichloromethane and 1 mL of trifluoroacetic acid (TFA) was stirred at room temperature for 3 h. The solvent was evaporated under reduced pressure and the oily substance obtained was used for further reactions without purification. In another round bottomed flask, N-phthaloyl-L-leucine (88 mg, 0.34 mmol) in dichloromethane (20 mL) along with triethylamine (TEA) (1 mL), N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDCHCl) (97 mg, 0.51 mmol) and anhydrous 1-hydroxybenzotriazole (HOBt) (69 mg, 0.51mmol) were stirred at 0°C for 1 h followed by addition of Boc-deprotected hydroxyethylamine diluted with dichloromethane (3 mL). This procedure was followed to prepare compounds 6aq. The reaction mixture was stirred at 0°C for another 30 minutes and then at room temperature for 24 h. The reaction mixture was concentrated under reduced pressure. The semi-solid material obtained was diluted with 25 mL of ethyl acetate and washed three times with distilled water. The organic layer obtained was dried over anhydrous Na2SO4 and solvent was evaporated under reduced pressure. The obtained compounds were purified by column chromatography using silica gel as stationary phase and chloroform-methanol (96:4) as eluent that afforded a white solid (6a-q) in fair to good yield (Table 2). The spectroscopic details are furnished in supporting information.To obtain 6r, 6t and 6u, a solution of Boc-protected bis-hydroxyethylpiperazine, 5f (171mg, 0.28 mmol) in 5 mL of dichloromethane and 1 mL of trifluoroacetic acid (TFA) was stirred at room temperature for 3 h. The solvent was evaporated under reduced pressure and the oily substance obtained was used for further reactions without purification. In another round bottomed flask, N-phthaloyl-L-amino acid (161 mg, 0.62 mmol) in dichloromethane (20 mL) along with triethylamine (TEA) (1 mL), N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC•HCl) (177 mg, 0.93 mmol) and anhydrous 1-hydroxybenzotriazole (HOBt) (125 mg, 0.93 mmol) were stirred at 0°C for 1 h followed by addition of Boc-deprotected hydroxyethyl piperazine diluted with dichloromethane (3 mL). The reaction mixture was stirred at 0°C for another 30 minutes and then at room temperature for 24 h. The reaction mixture was concentrated under reduced pressure. The semi-solid material obtained was diluted with 25 mL of ethyl acetate and washed three times with distilled water. The organic layer obtained was dried over anhydrous Na2SO4 and solvent was evaporated under reduced pressure. The obtained compounds were purified by column chromatography using silica gel as stationary phase and chloroform-methanol (96:4) as eluent that afforded a white solid (6r-u) in fair to good yield (Table 3). The spectroscopic details are furnished in supporting information. Compound 6s was prepared following literature procedure [30].

Reference： [1]Singh, Anil K.; Rathore, Sumit; Tang, Yan; Goldfarb, Nathan E.; Dunn, Ben M.; Rajendran, Vinoth; Ghosh, Prahlad C.; Singh, Neelu; Latha; Singh, Brajendra K.; Rawat, Manmeet; Rathi, Brijesh [PLoS ONE, 2015, vol. 10, # 10]

40
C₂₁H₂₈FN₃O [ No CAS ]
[ 6306-54-3 ]
C₃₄H₃₉FN₄O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: N-phthaloyl L-valine With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0℃; for 1h; Stage #2: C₂₁H₂₈FN₃O In dichloromethane at 0 - 20℃; for 24.5h;	General procedure for deprotection and coupling reaction with N-phthaloyl-L-aminoacids to afford 6a-6u. General procedure: A solution of Boc-protected hydroxyethylamines, 5a (101 mg, 0.28mmol) in 5 mL of dichloromethane and 1 mL of trifluoroacetic acid (TFA) was stirred at room temperature for 3 h. The solvent was evaporated under reduced pressure and the oily substance obtained was used for further reactions without purification. In another round bottomed flask, N-phthaloyl-L-leucine (88 mg, 0.34 mmol) in dichloromethane (20 mL) along with triethylamine (TEA) (1 mL), N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDCHCl) (97 mg, 0.51 mmol) and anhydrous 1-hydroxybenzotriazole (HOBt) (69 mg, 0.51mmol) were stirred at 0°C for 1 h followed by addition of Boc-deprotected hydroxyethylamine diluted with dichloromethane (3 mL). This procedure was followed to prepare compounds 6aq. The reaction mixture was stirred at 0°C for another 30 minutes and then at room temperature for 24 h. The reaction mixture was concentrated under reduced pressure. The semi-solid material obtained was diluted with 25 mL of ethyl acetate and washed three times with distilled water. The organic layer obtained was dried over anhydrous Na2SO4 and solvent was evaporated under reduced pressure. The obtained compounds were purified by column chromatography using silica gel as stationary phase and chloroform-methanol (96:4) as eluent that afforded a white solid (6a-q) in fair to good yield (Table 2). The spectroscopic details are furnished in supporting information.To obtain 6r, 6t and 6u, a solution of Boc-protected bis-hydroxyethylpiperazine, 5f (171mg, 0.28 mmol) in 5 mL of dichloromethane and 1 mL of trifluoroacetic acid (TFA) was stirred at room temperature for 3 h. The solvent was evaporated under reduced pressure and the oily substance obtained was used for further reactions without purification. In another round bottomed flask, N-phthaloyl-L-amino acid (161 mg, 0.62 mmol) in dichloromethane (20 mL) along with triethylamine (TEA) (1 mL), N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC•HCl) (177 mg, 0.93 mmol) and anhydrous 1-hydroxybenzotriazole (HOBt) (125 mg, 0.93 mmol) were stirred at 0°C for 1 h followed by addition of Boc-deprotected hydroxyethyl piperazine diluted with dichloromethane (3 mL). The reaction mixture was stirred at 0°C for another 30 minutes and then at room temperature for 24 h. The reaction mixture was concentrated under reduced pressure. The semi-solid material obtained was diluted with 25 mL of ethyl acetate and washed three times with distilled water. The organic layer obtained was dried over anhydrous Na2SO4 and solvent was evaporated under reduced pressure. The obtained compounds were purified by column chromatography using silica gel as stationary phase and chloroform-methanol (96:4) as eluent that afforded a white solid (6r-u) in fair to good yield (Table 3). The spectroscopic details are furnished in supporting information. Compound 6s was prepared following literature procedure [30].

Reference： [1]Singh, Anil K.; Rathore, Sumit; Tang, Yan; Goldfarb, Nathan E.; Dunn, Ben M.; Rajendran, Vinoth; Ghosh, Prahlad C.; Singh, Neelu; Latha; Singh, Brajendra K.; Rawat, Manmeet; Rathi, Brijesh [PLoS ONE, 2015, vol. 10, # 10]

41
C₂₁H₂₈BrN₃O [ No CAS ]
[ 6306-54-3 ]
C₃₄H₃₉BrN₄O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: N-phthaloyl L-valine With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0℃; for 1h; Stage #2: C₂₁H₂₈BrN₃O In dichloromethane at 0 - 20℃; for 24.5h;	General procedure for deprotection and coupling reaction with N-phthaloyl-L-aminoacids to afford 6a-6u. General procedure: A solution of Boc-protected hydroxyethylamines, 5a (101 mg, 0.28mmol) in 5 mL of dichloromethane and 1 mL of trifluoroacetic acid (TFA) was stirred at room temperature for 3 h. The solvent was evaporated under reduced pressure and the oily substance obtained was used for further reactions without purification. In another round bottomed flask, N-phthaloyl-L-leucine (88 mg, 0.34 mmol) in dichloromethane (20 mL) along with triethylamine (TEA) (1 mL), N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDCHCl) (97 mg, 0.51 mmol) and anhydrous 1-hydroxybenzotriazole (HOBt) (69 mg, 0.51mmol) were stirred at 0°C for 1 h followed by addition of Boc-deprotected hydroxyethylamine diluted with dichloromethane (3 mL). This procedure was followed to prepare compounds 6aq. The reaction mixture was stirred at 0°C for another 30 minutes and then at room temperature for 24 h. The reaction mixture was concentrated under reduced pressure. The semi-solid material obtained was diluted with 25 mL of ethyl acetate and washed three times with distilled water. The organic layer obtained was dried over anhydrous Na2SO4 and solvent was evaporated under reduced pressure. The obtained compounds were purified by column chromatography using silica gel as stationary phase and chloroform-methanol (96:4) as eluent that afforded a white solid (6a-q) in fair to good yield (Table 2). The spectroscopic details are furnished in supporting information.To obtain 6r, 6t and 6u, a solution of Boc-protected bis-hydroxyethylpiperazine, 5f (171mg, 0.28 mmol) in 5 mL of dichloromethane and 1 mL of trifluoroacetic acid (TFA) was stirred at room temperature for 3 h. The solvent was evaporated under reduced pressure and the oily substance obtained was used for further reactions without purification. In another round bottomed flask, N-phthaloyl-L-amino acid (161 mg, 0.62 mmol) in dichloromethane (20 mL) along with triethylamine (TEA) (1 mL), N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC•HCl) (177 mg, 0.93 mmol) and anhydrous 1-hydroxybenzotriazole (HOBt) (125 mg, 0.93 mmol) were stirred at 0°C for 1 h followed by addition of Boc-deprotected hydroxyethyl piperazine diluted with dichloromethane (3 mL). The reaction mixture was stirred at 0°C for another 30 minutes and then at room temperature for 24 h. The reaction mixture was concentrated under reduced pressure. The semi-solid material obtained was diluted with 25 mL of ethyl acetate and washed three times with distilled water. The organic layer obtained was dried over anhydrous Na2SO4 and solvent was evaporated under reduced pressure. The obtained compounds were purified by column chromatography using silica gel as stationary phase and chloroform-methanol (96:4) as eluent that afforded a white solid (6r-u) in fair to good yield (Table 3). The spectroscopic details are furnished in supporting information. Compound 6s was prepared following literature procedure [30].

Reference： [1]Singh, Anil K.; Rathore, Sumit; Tang, Yan; Goldfarb, Nathan E.; Dunn, Ben M.; Rajendran, Vinoth; Ghosh, Prahlad C.; Singh, Neelu; Latha; Singh, Brajendra K.; Rawat, Manmeet; Rathi, Brijesh [PLoS ONE, 2015, vol. 10, # 10]

42
C₂₄H₃₆N₄O₂ [ No CAS ]
[ 6306-54-3 ]
C₅₀H₅₈N₆O₈ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: N-phthaloyl L-valine With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0℃; for 1h; Stage #2: C₂₄H₃₆N₄O₂ In dichloromethane at 0 - 20℃; for 24.5h;	General procedure for deprotection and coupling reaction with N-phthaloyl-L-aminoacids to afford 6a-6u. General procedure: A solution of Boc-protected hydroxyethylamines, 5a (101 mg, 0.28mmol) in 5 mL of dichloromethane and 1 mL of trifluoroacetic acid (TFA) was stirred at room temperature for 3 h. The solvent was evaporated under reduced pressure and the oily substance obtained was used for further reactions without purification. In another round bottomed flask, N-phthaloyl-L-leucine (88 mg, 0.34 mmol) in dichloromethane (20 mL) along with triethylamine (TEA) (1 mL), N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDCHCl) (97 mg, 0.51 mmol) and anhydrous 1-hydroxybenzotriazole (HOBt) (69 mg, 0.51mmol) were stirred at 0°C for 1 h followed by addition of Boc-deprotected hydroxyethylamine diluted with dichloromethane (3 mL). This procedure was followed to prepare compounds 6aq. The reaction mixture was stirred at 0°C for another 30 minutes and then at room temperature for 24 h. The reaction mixture was concentrated under reduced pressure. The semi-solid material obtained was diluted with 25 mL of ethyl acetate and washed three times with distilled water. The organic layer obtained was dried over anhydrous Na2SO4 and solvent was evaporated under reduced pressure. The obtained compounds were purified by column chromatography using silica gel as stationary phase and chloroform-methanol (96:4) as eluent that afforded a white solid (6a-q) in fair to good yield (Table 2). The spectroscopic details are furnished in supporting information.To obtain 6r, 6t and 6u, a solution of Boc-protected bis-hydroxyethylpiperazine, 5f (171mg, 0.28 mmol) in 5 mL of dichloromethane and 1 mL of trifluoroacetic acid (TFA) was stirred at room temperature for 3 h. The solvent was evaporated under reduced pressure and the oily substance obtained was used for further reactions without purification. In another round bottomed flask, N-phthaloyl-L-amino acid (161 mg, 0.62 mmol) in dichloromethane (20 mL) along with triethylamine (TEA) (1 mL), N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC•HCl) (177 mg, 0.93 mmol) and anhydrous 1-hydroxybenzotriazole (HOBt) (125 mg, 0.93 mmol) were stirred at 0°C for 1 h followed by addition of Boc-deprotected hydroxyethyl piperazine diluted with dichloromethane (3 mL). The reaction mixture was stirred at 0°C for another 30 minutes and then at room temperature for 24 h. The reaction mixture was concentrated under reduced pressure. The semi-solid material obtained was diluted with 25 mL of ethyl acetate and washed three times with distilled water. The organic layer obtained was dried over anhydrous Na2SO4 and solvent was evaporated under reduced pressure. The obtained compounds were purified by column chromatography using silica gel as stationary phase and chloroform-methanol (96:4) as eluent that afforded a white solid (6r-u) in fair to good yield (Table 3). The spectroscopic details are furnished in supporting information. Compound 6s was prepared following literature procedure [30].

Reference： [1]Singh, Anil K.; Rathore, Sumit; Tang, Yan; Goldfarb, Nathan E.; Dunn, Ben M.; Rajendran, Vinoth; Ghosh, Prahlad C.; Singh, Neelu; Latha; Singh, Brajendra K.; Rawat, Manmeet; Rathi, Brijesh [PLoS ONE, 2015, vol. 10, # 10]

43
[ 70931-28-1 ]
[ 6306-54-3 ]
(S)-2-(1-(4-(4-fluorobenzyl)piperazin-1-yl)-3-methyl-1-oxobutan-2-yl)isoindoline-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: N-phthaloyl L-valine With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0℃; for 0.25h; Stage #2: With benzotriazol-1-ol In dichloromethane at 0℃; for 0.25h; Stage #3: 1-(4-fluorophenylmethyl)piperazine In dichloromethane at 20℃; for 24h;	2.1 General synthetic procedure for compounds (3a-e) General procedure: To the solution of N-phthaloyl-L-amino acid (0.4 mmol) in dichloromethane (20 mL), N-(3-Dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (EDC·HCl) (0.6 mmol) and triethylamine (TEA, 1.6 mmol) were added and the contents were stirred at 0 °C for 15 min to secure homogeneous mixture. Subsequently, Hydroxybenzotriazole (HOBt) (0.6 mmol) was added to the reaction mixture and stirred for another 15 min at 0 °C. N-substituted piperazines (0.48 mmol) were added and the reaction mixture was further stirred for 24 h at room temperature. The solvent was evaporated under reduced pressure and the reaction mixture was extracted with ethyl acetate and water. The organic layer was concentrated and purified by column chromatography (ethyl acetate/petroleum ether, 4:6.

Reference： [1]Singh, Anil K.; Rathi, Brijesh; Medviediev, Volodymyr V.; Shishkin, Oleg V.; Bahadur, Vijay; Singh, Taruna; Singh, Brajendra K.; Vijayan; Balachandran; Gorobets, Nikolay Yu [Journal of Chemical Sciences, 2016, vol. 128, # 2, p. 297 - 309]

44
[ 5680-80-8 ]
[ 6306-54-3 ]
methyl N-phthaloyl-L-valinyl-L-serinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	With dmap; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 20℃; for 18h;	22 4.22 Synthesis of methyl N-phthaloyl-L-valinyl-L-serinate (33). N-Phthaloyl-L-valine (3.709 g, 15.0 mmol) and methyl L-serinate hydrochloride (2.334 g, 15.0 mmol) were dissolved in DMF (peptide synthesis grade) (30 mL) and treated with DIPEA (10.2 mL, 60.0 mmol, 4.0 equiv) under stirring. Furthermore, HOBt (2.757 g, 18.0 mmol, 1.2 equiv), DMAP (0.183 g, 1.5 mmol, 0.1 equiv) and DCC (3.714 g, 18.0 mmol, 1.2 equiv) were added and the solution stirred at r.t. for 18 h, while the formation of a white precipitate was observed after some minutes. For the workup, EtOAc (80 mL) was added and the solution washed with 1 m aq. HCl, water (50 mL each) and brine (2 * 50 mL). The organic phases were combined, dried over MgSO4 and the solvent removed under reduced pressure. The obtained yellow oil was dissolved in hot Et2O with a little EtOAc and the solution stored in the fridge. The product precipitated as a colorless solid. A second fraction of product could be isolated from the mother liquor. Yield: 2.651 g (51%). Mp 158-161 °C (dec.). = 29.9 (c = 0.91, CHCl3). 1H NMR (400 MHz, CDCl3, 298 K): δ = 0.88 (d, 3JH,H = 6.7 Hz, 3H, iPr-CH3), 1.11 (d, 3JH,H = 6.7 Hz, 3H, iPr-CH3), 2.94 (dsept, 3JH,H = 10.5, 6.8 Hz, 1H, iPr-CH), 3.69 (s, 3H, OCH3), 3.82 (m, 2H, CH2OH), 4.47 (d, 3JH,H = 10.5 Hz, 1H, PhthNCH), 4.50 (t, 3JH,H = 4.3 Hz, 1H, CHCO2Me), 7.82-7.86 (m, 2H, CCHCH), 7.87-7.91 (m, 2H, CCH). 13C NMR (101 MHz, CDCl3, 298 K): δ = 19.8 (q, iPr-CH3), 20.5 (q, iPr-CH3), 28.7 (d, iPr-CH), 52.9 (q, OCH3), 56.4 (d, CHCO2Me), 62.6 (t, CH2OH), 62.7 (d, PhthNCH), 124.5 (d, CCH), 132.8 (s, NCOC), 135.8 (d, CCHCH), 169.6 (s, NCOC), 171.4 (s, CHCON), 172.1 (s, CO2). HRMS: [M+H]+, calcd for C17H20N2O6H+: 349.1394, found: 349.1383; [M+Na]+, calcd for C17H20N2O6Na+: 371.1214, found: 371.1204.

Reference： [1]Ulbrich, Dirk; Daniliuc, Constantin G.; Haufe, Günter [Journal of Fluorine Chemistry, 2016, vol. 188, p. 65 - 75]

45
[ 91345-62-9 ]
[ 6306-54-3 ]
(S)-2-(1-(4-(4-bromobenzyl)piperazin-1-yl)-3-methyl-1-oxobutan-2-yl)isoindoline-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	Stage #1: N-phthaloyl L-valine With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0℃; for 0.25h; Stage #2: With benzotriazol-1-ol In dichloromethane at 0℃; for 0.25h; Stage #3: 1-(4-bromobenzyl)piperazine In dichloromethane at 20℃; for 24h;	2.1b General procedure for synthesis of phthalimides (3a-t): General procedure: To the solution of N-phthaloyl-L-amino acid (0.4 mmol) in dichloromethane (20 mL), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride, EDC·HCl (0.6 mmol) and triethylamine, TEA (1.6 mmol) were added and the contents were stirred at 0C for 15 min to secure homogenous reaction mixture. Subsequently, HOBt (0.6 mmol) was added to the reaction mixture and stirring was continued for another 15 min atthe same temperature. N-substituted piperazine derivative (0.48 mmol) was added and reaction mixture was stirred for 24 h at room temperature. The solvent was evaporated under reduced pressure and the reaction contents were extracted with ethyl acetate and water. The organic layer was collected separately, concentrated under reduced pressure and purified by column chromatography(ethylacetate/petroleum ether, 4:6). Phthalimides(3a, 3e, 3g, 3i and 3m) have been previously prepared by our team and their structural aspects were investigated for nonlinear optical property.37 All the compounds were characterized by spectroscopic tools and the corresponding spectroscopic data are described in supporting information.

Reference： [1]Singh, Anil K; Bhardwaj, Jitender K; Olival, Ana; Kumar, Yogesh; Podder, Avijit; Maheshwari, Ankur; Agrawal, Renuka; Latha; Singh, Brajendra K; Tomás, Helena; Rodrigues, João; Kishan, Ram; Rupini; Rathi, Brijesh [Journal of Chemical Sciences, 2016, vol. 128, # 8, p. 1245 - 1263]

46
[ 107890-32-4 ]
[ 6306-54-3 ]
(S)-2-(3-methyl-1-oxo-1-(4-(4-(trifluoromethyl)benzyl)piperazin-1-yl)butan-2-yl)isoindoline-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	Stage #1: N-phthaloyl L-valine With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0℃; for 0.25h; Stage #2: With benzotriazol-1-ol In dichloromethane at 0℃; for 0.25h; Stage #3: 1-(4-trifluoromethylbenzyl)piperazine In dichloromethane at 20℃; for 24h;	2.1b General procedure for synthesis of phthalimides (3a-t): General procedure: To the solution of N-phthaloyl-L-amino acid (0.4 mmol) in dichloromethane (20 mL), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride, EDC·HCl (0.6 mmol) and triethylamine, TEA (1.6 mmol) were added and the contents were stirred at 0C for 15 min to secure homogenous reaction mixture. Subsequently, HOBt (0.6 mmol) was added to the reaction mixture and stirring was continued for another 15 min atthe same temperature. N-substituted piperazine derivative (0.48 mmol) was added and reaction mixture was stirred for 24 h at room temperature. The solvent was evaporated under reduced pressure and the reaction contents were extracted with ethyl acetate and water. The organic layer was collected separately, concentrated under reduced pressure and purified by column chromatography(ethylacetate/petroleum ether, 4:6). Phthalimides(3a, 3e, 3g, 3i and 3m) have been previously prepared by our team and their structural aspects were investigated for nonlinear optical property.37 All the compounds were characterized by spectroscopic tools and the corresponding spectroscopic data are described in supporting information.

Reference： [1]Singh, Anil K; Bhardwaj, Jitender K; Olival, Ana; Kumar, Yogesh; Podder, Avijit; Maheshwari, Ankur; Agrawal, Renuka; Latha; Singh, Brajendra K; Tomás, Helena; Rodrigues, João; Kishan, Ram; Rupini; Rathi, Brijesh [Journal of Chemical Sciences, 2016, vol. 128, # 8, p. 1245 - 1263]

47
[ 956-61-6 ]
[ 6306-54-3 ]
(S)-2-(1-(4-(4-(tert-butyl)benzyl)piperazin-1-y)-3-methyl-1-oxobutan-2-yl)isoindoline-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	Stage #1: N-phthaloyl L-valine With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0℃; for 0.25h; Stage #2: With benzotriazol-1-ol In dichloromethane at 0℃; for 0.25h; Stage #3: 1-(4-tert-butylbenzyl)piperazine In dichloromethane at 20℃; for 24h;	2.1b General procedure for synthesis of phthalimides (3a-t): General procedure: To the solution of N-phthaloyl-L-amino acid (0.4 mmol) in dichloromethane (20 mL), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride, EDC·HCl (0.6 mmol) and triethylamine, TEA (1.6 mmol) were added and the contents were stirred at 0C for 15 min to secure homogenous reaction mixture. Subsequently, HOBt (0.6 mmol) was added to the reaction mixture and stirring was continued for another 15 min atthe same temperature. N-substituted piperazine derivative (0.48 mmol) was added and reaction mixture was stirred for 24 h at room temperature. The solvent was evaporated under reduced pressure and the reaction contents were extracted with ethyl acetate and water. The organic layer was collected separately, concentrated under reduced pressure and purified by column chromatography(ethylacetate/petroleum ether, 4:6). Phthalimides(3a, 3e, 3g, 3i and 3m) have been previously prepared by our team and their structural aspects were investigated for nonlinear optical property.37 All the compounds were characterized by spectroscopic tools and the corresponding spectroscopic data are described in supporting information.

Reference： [1]Singh, Anil K; Bhardwaj, Jitender K; Olival, Ana; Kumar, Yogesh; Podder, Avijit; Maheshwari, Ankur; Agrawal, Renuka; Latha; Singh, Brajendra K; Tomás, Helena; Rodrigues, João; Kishan, Ram; Rupini; Rathi, Brijesh [Journal of Chemical Sciences, 2016, vol. 128, # 8, p. 1245 - 1263]

48
[ 5321-49-3 ]
[ 6306-54-3 ]
(S)-2-(3-methyl-1-oxo-1-(4-phenethylpiperazin-1-yl)butan-2-yl)isoindoline-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	Stage #1: N-phthaloyl L-valine With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0℃; for 0.25h; Stage #2: With benzotriazol-1-ol In dichloromethane at 0℃; for 0.25h; Stage #3: 4-(phenethyl)piperazine In dichloromethane at 20℃; for 24h;	2.1b General procedure for synthesis of phthalimides (3a-t): General procedure: To the solution of N-phthaloyl-L-amino acid (0.4 mmol) in dichloromethane (20 mL), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride, EDC·HCl (0.6 mmol) and triethylamine, TEA (1.6 mmol) were added and the contents were stirred at 0C for 15 min to secure homogenous reaction mixture. Subsequently, HOBt (0.6 mmol) was added to the reaction mixture and stirring was continued for another 15 min atthe same temperature. N-substituted piperazine derivative (0.48 mmol) was added and reaction mixture was stirred for 24 h at room temperature. The solvent was evaporated under reduced pressure and the reaction contents were extracted with ethyl acetate and water. The organic layer was collected separately, concentrated under reduced pressure and purified by column chromatography(ethylacetate/petroleum ether, 4:6). Phthalimides(3a, 3e, 3g, 3i and 3m) have been previously prepared by our team and their structural aspects were investigated for nonlinear optical property.37 All the compounds were characterized by spectroscopic tools and the corresponding spectroscopic data are described in supporting information.

Reference： [1]Singh, Anil K; Bhardwaj, Jitender K; Olival, Ana; Kumar, Yogesh; Podder, Avijit; Maheshwari, Ankur; Agrawal, Renuka; Latha; Singh, Brajendra K; Tomás, Helena; Rodrigues, João; Kishan, Ram; Rupini; Rathi, Brijesh [Journal of Chemical Sciences, 2016, vol. 128, # 8, p. 1245 - 1263]

49
[ 76203-05-9 ]
[ 6306-54-3 ]
methyl 4-phenyl-1-((1,3-dioxisoindolin-2-yl)isobutyl)isoquinoline-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With potassium phosphate; dipotassium peroxodisulfate; silver carbonate In water; acetonitrile at 70℃; for 4h; Inert atmosphere;

Reference： [1]Yao, Qian; Zhou, Xin; Zhang, Xiuli; Wang, Cong; Wang, Peng; Li, Ming [Organic and Biomolecular Chemistry, 2017, vol. 15, # 4, p. 957 - 971]

50
[ 1428264-89-4 ]
[ 6306-54-3 ]
2-methyl-6-((1,3-dioxisoindolin-2-yl)isopropyl)phenanthridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With potassium phosphate; dipotassium peroxodisulfate; silver carbonate In water; acetonitrile at 70℃; for 4h; Inert atmosphere;

Reference： [1]Yao, Qian; Zhou, Xin; Zhang, Xiuli; Wang, Cong; Wang, Peng; Li, Ming [Organic and Biomolecular Chemistry, 2017, vol. 15, # 4, p. 957 - 971]

51
[ 14148-42-6 ]
[ 6306-54-3 ]
(S)-2-(1,3-dioxoisoindolin-2-yl)-3-methyl-N-(quinolin-8-yl)butanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: N-phthaloyl L-valine With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane for 1.5h; Stage #2: 8-hydrazinoquinoline With triethylamine In dichloromethane	The reaction conditions are the compound of formula II: oxalyl chloride with a molar ratio of 1 • 8 i human amount 1 into the elixir C, DMF is added for catalytic cutting, and the reaction is carried out at room temperature and under stirring for 21 . Dry, float the intermediate product; Rongzhou C: It is dichloromethane, the added amount of DMF is 1 drop; the concentration of the compound of formula II in solvent C is lmql / l4, and then the intermediate product, R3NHb and Triethylamine is added to Λ solvent D together, and the reaction is carried out under normal temperature and stirring conditions to obtain a compound of formula III: Chiral 3 1 :: _ triethylamine: The compound of formula II has a molar ratio of 0. 8H and D is dichloro. Methane.

Reference： [1]Current Patent Assignee: NANKAI UNIVERSITY - CN109970713, 2019, A Location in patent: Paragraph 0073

52
[ 6306-54-3 ]
(R)-2-(1,3-dioxoisoindolin-2-yl)-3-fluoro-3-methylbutanoic acid, [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With Selectfluor In acetonitrile for 21h; Inert atmosphere; Electrolysis;	Step 2: Synthesis of (R)-2-(1,3-dioxoisoindolin-2-yl)-3-fluoro-3-methylbutanoic acid, 12 To a clean and dry homemade PVC electrolysis cell (37 cm × 34 cm × 7 cm), equipped with two RVCelectrodes (30 cm × 30 cm, 100 ppi, each having a 30 cm × 16 cm immersion area) and connected to anEC-Workstation, was added (S)-2-(1,3-dioxoisoindolin-2-yl)-3-methylbutanoic acid (27, 100.00 g, 0.4mol, 1.0 equiv), Selectfluor (283.2 g, 0.8 mol, 2.0 equiv) and MeCN (4 L). The resulting solution wasthen degassed using nitrogen gas for 30 min, then electrolyzed with a constant current (2 mA/cm2) undernitrogen atmosphere for 21 h. After 27 was completely consumed (2.5 F/mol total current), the solventwas removed under reduced pressure. The residual solid was diluted with EtOAc (500 mL) and theinsoluble salt was filtered off through a Buchner funnel. The filtrate was washed with water (3 × 1.2 L),dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The residue was purifiedby flash chromatography (EtOAc:hexane = 1:8) to afford desired product 12 (81 g, 76% isolated yield) asa white solid. See Figure S3 for further information.
65%	With sodium nitrate; Selectfluor In acetonitrile Inert atmosphere; Electrolysis;	General procedure for small scale fluorination using IKA ElectraSyn 2.0 General procedure: Unless otherwise specified, the reaction was carried out on 0.3 mmol scale. To a 5 mL undivided ElectraSyn vial equipped with a stirrer bar was added substrate (0.30 mmol), Selectfluor (A, 3.0 equiv,319 mg, 0.90 mmol), NaNO3 (0.2 equiv, 5.1 mg, 0.06 mmol), and MeCN (3.0 mL). The vial cap equippedwith a pair of RVC electrodes was screwed on, and headspace of the vial was purged with Ar using aballoon, syringe and needle assembly prior to electrolysis. Reaction parameters of ElectraSyn device were set up as follows: constant current, 3.0 mA; no referenceelectrode; total charge, 0.30 mmol substrate, ranging from 0.25 to 3.0 F/mol; alternate polarity, 2 min;stirring, 600 rpm. The mixture was electrolyzed under Ar atmosphere until complete or reasonable consumption of thestarting material as judged by TLC. After electrolysis, the cap was removed, and the electrodes weretaken out and rinsed with MeCN into the reaction mixture [19F NMR data of an aliquot in MeCN may becollected without deuterium lock]. The reaction mixture was poured into saturated aqueous NaHCO3 (orH2O for 5, 12, 15, 17, and 19) and extracted with CH2Cl2. The combined organics were washed with brine,dried over anhydrous Na2SO4 and concentrated in vacuo [Crude 1H and 19F NMR data in CDCl3 may becollected here]. The crude material was purified by silica gel column chromatography or preparative thinlayerchromatography to furnish the desired product. See Figure S2 for graphical guides.

Reference： [1]Baran, Phil S.; Chen, Longrui; Chen, Miao; Hoshikawa, Tamaki; Kawamata, Yu; Li, Chao; Mykhailiuk, Pavel; Nakamura, Hugh; Peters, Byron K.; Reisberg, Solomon H.; Shibuguchi, Tomoyuki; Takahira, Yusuke [Synlett, 2019, vol. 30, # 10, p. 1178 - 1182]
[2]Baran, Phil S.; Chen, Longrui; Chen, Miao; Hoshikawa, Tamaki; Kawamata, Yu; Li, Chao; Mykhailiuk, Pavel; Nakamura, Hugh; Peters, Byron K.; Reisberg, Solomon H.; Shibuguchi, Tomoyuki; Takahira, Yusuke [Synlett, 2019, vol. 30, # 10, p. 1178 - 1182]

53
[ 40216-83-9 ]
[ 6306-54-3 ]
C₁₉H₂₂N₂O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: N-phthaloyl L-valine With N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 0.0833333h; Inert atmosphere; Stage #2: L-4-hydroxyproline methyl ester hydrochloride With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide Inert atmosphere;

Reference： [1]Baran, Phil S.; Carlson, Ethan; Edwards, Jacob T.; Hayashi, Kyohei; Kawamata, Yu; Saito, Masato; Shaji, Shobin; Simmons, Bryan J.; Waldmann, Dirk; Zapf, Christoph W. [Journal of the American Chemical Society, 2021, vol. 143, # 40, p. 16580 - 16588]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	6306-54-3	MDL No. :	MFCD00191000
Formula :	C₁₃H₁₃NO₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	UUIPGCXIZVZSEC-JTQLQIEISA-N
M.W :	247.25	Pubchem ID :	229337
Synonyms :

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P301+P312-P302+P352-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-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:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 6306-54-3 ] {[proInfo.proName]}

Quality Control of [ 6306-54-3 ]

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[ 6306-54-3 ] Synthesis Path-Downstream 1~53

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[ 6306-54-3 ]

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[ CAS No. 6306-54-3 ] {[proInfo.proName]}

Quality Control of [ 6306-54-3 ]

Related Doc. of [ 6306-54-3 ]

Product Details of [ 6306-54-3 ]

Safety of [ 6306-54-3 ]

Application In Synthesis of [ 6306-54-3 ]

[ 6306-54-3 ] Synthesis Path-Downstream 1~53

Related Functional Groups of [ 6306-54-3 ]

Amino Acid Derivatives

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 6306-54-3 ]