Name: 359860-27-8|N-(2-(2-(2-(2-Aminoethoxy)ethoxy)ethoxy)ethyl)-5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide|95%
Brand: Ambeed
SKU: A444152
Rating: 97 (29 reviews)

1
Cellobiose [ No CAS ]
[ 359860-27-8 ]
[ 418759-46-3 ]

Yield	Reaction Conditions	Operation in experiment
19%	Stage #1: Cellobiose; N-(2-(2-(2-(2-amidoethoxy)ethoxy)ethoxy)ethoxy)biotinamide In methanol; water at 20 - 55℃; Stage #2: With sodium tetrahydroborate In methanol; water at 20℃;

Reference： [1]McReynolds, Katherine D.; Bhat, Abhijit; Conboy, John C.; Saavedra; Gervay-Hague, Jacquelyn [Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 3, p. 625 - 637]

2
Lactose [ No CAS ]
[ 359860-27-8 ]
[ 418759-45-2 ]

Yield	Reaction Conditions	Operation in experiment
33%	Stage #1: Lactose; N-(2-(2-(2-(2-amidoethoxy)ethoxy)ethoxy)ethoxy)biotinamide In methanol; water at 20 - 55℃; Stage #2: With sodium tetrahydroborate In methanol; water at 20℃;

Reference： [1]McReynolds, Katherine D.; Bhat, Abhijit; Conboy, John C.; Saavedra; Gervay-Hague, Jacquelyn [Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 3, p. 625 - 637]

3
[ 13299-20-2 ]
[ 359860-27-8 ]
11-D-biotinamide-N-[3,6,9-trioxaundecane]-1-amino-1-deoxymelitol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
37%	Stage #1: melibiose; N-(2-(2-(2-(2-amidoethoxy)ethoxy)ethoxy)ethoxy)biotinamide In methanol; water at 20 - 55℃; Stage #2: With sodium tetrahydroborate In methanol; water at 20℃;

Reference： [1]McReynolds, Katherine D.; Bhat, Abhijit; Conboy, John C.; Saavedra; Gervay-Hague, Jacquelyn [Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 3, p. 625 - 637]

4
[ 418759-44-1 ]
[ 359860-27-8 ]

Yield	Reaction Conditions	Operation in experiment
52%	With reaget K²⁵ at 20℃; for 1.5h;
	With trifluoroacetic acid In dichloromethane at 20℃;

Reference： [1]McReynolds, Katherine D.; Bhat, Abhijit; Conboy, John C.; Saavedra; Gervay-Hague, Jacquelyn [Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 3, p. 625 - 637]
[2]Han, Xin; Wang, Chao; Qin, Chong; Xiang, Weiguo; Fernandez-Salas, Ester; Yang, Chao-Yie; Wang, Mi; Zhao, Lijie; Xu, Tianfeng; Chinnaswamy, Krishnapriya; Delproposto, James; Stuckey, Jeanne; Wang, Shaomeng [Journal of Medicinal Chemistry, 2019, vol. 62, # 2, p. 941 - 964]

5
[ 359860-27-8 ]
(S)-1-(3,3-Dimethyl-2-oxo-pentanoyl)-piperidine-2-carboxylic acid (R)-3-(3,4-dimethoxy-phenyl)-1-[3-(2,5-dioxo-pyrrolidin-1-yloxycarbonylmethoxy)-phenyl]-propyl ester [ No CAS ]
1-(3,3-dimethyl-2-oxo-pentanoyl)-piperidine-2-carboxylic acid 3-(3,4-dimethoxy-phenyl)-1-[3-({2-[2-(2-{2-[5-(2-oxo-hexahydro-thieno[3,4-d]imidazol-6-yl)-pentanoylamino]-ethoxy}-ethoxy)-ethoxy]-ethylcarbamoyl}-methoxy)-phenyl]-propyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	With triethylamine In dimethyl sulfoxide at 20℃; for 1h;

Reference： [1]McKenzie, Kathleen M.; Videlock, Elizabeth J.; Splittgerber, Ute; Austin, David J. [Angewandte Chemie - International Edition, 2004, vol. 43, # 31, p. 4052 - 4055]

6
[ 218600-44-3 ]
[ 359860-27-8 ]
11-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,3,4,5,6,6a,6b,7,8,8a,9,10,12a,14,14a,14b-hexadecahydro-2H-picene-4a-carboxylic acid {2-[2-(2-{2-[5-(2-oxo-hexahydro-thieno[3,4-d]imidazol-6-yl)-pentanoylamino]-ethoxy}-ethoxy)-ethoxy]-ethyl}-amide [ No CAS ]

Reference： [1]Molecular Pharmacology,2006,vol. 69,p. 1182 - 1193

7
[ 929-75-9 ]
[ 359860-27-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 45 percent / DMAP / tetrahydrofuran / 3 h / 20 °C 2: 503 mg / TEA / dimethylformamide / 20 h 3: 52 percent / reaget K²⁵ / 1.5 h / 20 °C

Reference： [1]McReynolds, Katherine D.; Bhat, Abhijit; Conboy, John C.; Saavedra; Gervay-Hague, Jacquelyn [Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 3, p. 625 - 637]

8
[ 120550-35-8 ]
[ 359860-27-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2002,vol. 10,p. 625 - 637

9
[ 101187-40-0 ]
[ 359860-27-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2002,vol. 10,p. 625 - 637
[2]Journal of Medicinal Chemistry,2019,vol. 62,p. 941 - 964

10
[ 58-85-5 ]
[ 359860-27-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: TEA / dimethylformamide / 4 h / 0 - 20 °C 2: 503 mg / TEA / dimethylformamide / 20 h 3: 52 percent / reaget K²⁵ / 1.5 h / 20 °C

Reference： [1]McReynolds, Katherine D.; Bhat, Abhijit; Conboy, John C.; Saavedra; Gervay-Hague, Jacquelyn [Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 3, p. 625 - 637]

11
[ 359860-27-8 ]
11-D-biotinamide-N-[3,6,9-trioxaundecane]-N-palmitoyl-1-amino-1-deoxymelitol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: methanol; H₂O / 20 - 55 °C 1.2: 37 percent / NaBH₄ / methanol; H₂O / 20 °C 2.1: 1.4 mg / TEA / dimethylformamide; CH₂Cl₂ / 20 °C

Reference： [1]McReynolds, Katherine D.; Bhat, Abhijit; Conboy, John C.; Saavedra; Gervay-Hague, Jacquelyn [Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 3, p. 625 - 637]

12
[ 359860-27-8 ]
11-D-biotinamide-N-[3,6,9-trioxaundecane]-N-palmitoyl-1-amino-1-deoxycellitol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: methanol; H₂O / 20 - 55 °C 1.2: 19 percent / NaBH₄ / methanol; H₂O / 20 °C 2.1: 2.6 mg / TEA / dimethylformamide; CH₂Cl₂ / 20 °C

Reference： [1]McReynolds, Katherine D.; Bhat, Abhijit; Conboy, John C.; Saavedra; Gervay-Hague, Jacquelyn [Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 3, p. 625 - 637]

13
[ 359860-27-8 ]
11-D-biotinamide-N-[3,6,9-trioxaundecane]-N-palmitoyl-1-amino-1-deoxylactitol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: methanol; H₂O / 20 - 55 °C 1.2: 33 percent / NaBH₄ / methanol; H₂O / 20 °C 2.1: 2.7 mg / TEA / dimethylformamide; CH₂Cl₂ / 20 °C

Reference： [1]McReynolds, Katherine D.; Bhat, Abhijit; Conboy, John C.; Saavedra; Gervay-Hague, Jacquelyn [Bioorganic and Medicinal Chemistry, 2002, vol. 10, # 3, p. 625 - 637]

14
[ 30562-34-6 ]
[ 359860-27-8 ]
C₄₆H₇₀N₆O₁₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol at 20℃;	6 Compound 6. To a solution of geldanamycin (56 mg, 0.1 mmol) in methanol (4 mL) at 20° C. was added Biotin-PEO-LC-amine (Pierce, Rockford, Ill.; 0.2 mmol). The mixture was stirred at 20° C. until the geldanamycin was fully consumed as indicated by TLC. The crude product was purified either by flash chromatography or by reversed-phase HPLC, giving compound 6 as a purple solid. ESI TOF MS m/z 947.4799, calculated for C46H71N6O12S ([M+H]+) 947.4794.

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US2005/267046, 2005, A1 Location in patent: Page/Page column 14

15
[ 875770-34-6 ]
[ 359860-27-8 ]

Yield	Reaction Conditions	Operation in experiment
88%	With water; triphenylphosphine In tetrahydrofuran at 20℃; for 12h;
	With water; triphenylphosphine In tetrahydrofuran at 20℃; for 12h; Inert atmosphere;
	With palladium 10% on activated carbon; hydrogen In methanol; water at 20℃;	4.1.6 N-(2-[2-{2-(2-Aminoethoxy)ethoxy}ethoxy]ethyl)-5-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanamide (15) To the solution of 14 (116.0 mg, 0.26 mmol) in MeOH (2.0 mL) was added 10% Pd-C (wetted with ca. 55% water, 160.0 mg). After being stirred at rt overnight under H2 atmosphere, the mixture was filtered through a celite pad and concentrated. The crude product was used for the next step without further purification.

With 5%-palladium/activated carbon; hydrogen In ethanol at 20℃; for 12h;

Reference： [1]Fusz, Stefan; Srivatsan, Seergazhi G.; Ackermann, Damian; Famulok, Michael [Journal of Organic Chemistry, 2008, vol. 73, # 13, p. 5069 - 5077]
[2]Yang, Peng-Yu; Liu, Kai; Zhang, Chongjing; Chen, Grace Y. J.; Shen, Yuan; Ngai, Mun Hong; Lear, Martin J.; Yao, Shao Q. [Chemistry - An Asian Journal, 2011, vol. 6, # 10, p. 2762 - 2775]
[3]Mizuhara, Tsukasa; Oishi, Shinya; Ohno, Hiroaki; Shimura, Kazuya; Matsuoka, Masao; Fujii, Nobutaka [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 7, p. 2079 - 2087]
[4]Current Patent Assignee: STATE UNIVERSITY OF NEW YORK - WO2015/38493, 2015, A1 Location in patent: Paragraph 0081

16
[ 619-21-6 ]
[ 359860-27-8 ]
[ 1039151-92-2 ]

Yield	Reaction Conditions	Operation in experiment
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide; acetonitrile at 20℃; for 2.5h;

Reference： [1]Fusz, Stefan; Srivatsan, Seergazhi G.; Ackermann, Damian; Famulok, Michael [Journal of Organic Chemistry, 2008, vol. 73, # 13, p. 5069 - 5077]

17
[ 616-76-2 ]
[ 359860-27-8 ]
C₂₆H₃₈N₄O₈S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide; acetonitrile at 20℃; for 2.5h;

Reference： [1]Fusz, Stefan; Srivatsan, Seergazhi G.; Ackermann, Damian; Famulok, Michael [Journal of Organic Chemistry, 2008, vol. 73, # 13, p. 5069 - 5077]

18
[ 3006-96-0 ]
[ 359860-27-8 ]
C₂₆H₄₀N₄O₇S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide; acetonitrile at 20℃; for 2.5h;

Reference： [1]Fusz, Stefan; Srivatsan, Seergazhi G.; Ackermann, Damian; Famulok, Michael [Journal of Organic Chemistry, 2008, vol. 73, # 13, p. 5069 - 5077]

19
[ 619-66-9 ]
[ 359860-27-8 ]
[ 889443-90-7 ]

Yield	Reaction Conditions	Operation in experiment
50%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide; acetonitrile at 20℃; for 2.5h;

Reference： [1]Fusz, Stefan; Srivatsan, Seergazhi G.; Ackermann, Damian; Famulok, Michael [Journal of Organic Chemistry, 2008, vol. 73, # 13, p. 5069 - 5077]

20
C₂₁H₂₃N₃O₅ [ No CAS ]
[ 359860-27-8 ]
[ 1115219-78-7 ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane; N,N-dimethyl-formamide Inert atmosphere;

Reference： [1]Location in patent: experimental part Kuramochi, Kouji; Aoki, Toshiaki; Nakazaki, Atsuo; Kamisuki, Shinji; Takeno, Masahiro; Ohnishi, Kensuke; Kimoto, Kuniaki; Watanabe, Nobuo; Kamakura, Takashi; Arai, Takao; Sugawara, Fumio; Kobayashi, Susumu [Synthesis, 2008, # 23, p. 3810 - 3818]

21
[ 1193687-08-9 ]
[ 359860-27-8 ]
[ 1193687-03-4 ]

Yield	Reaction Conditions	Operation in experiment
6.3 mg	Stage #1: 3-((S,Z)-1-ethyl-4-(1-hydroxypentylidene)-3,5-dioxopyrrolidin-2-yl)propanoic acid With benzotriazol-1-ol In tetrahydrofuran; dichloromethane at 0℃; for 0.166667h; Stage #2: N-(2-(2-(2-(2-amidoethoxy)ethoxy)ethoxy)ethoxy)biotinamide With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran; dichloromethane at 0 - 20℃;

Reference： [1]Knoth, Tanja; Warburg, Karin; Katzka, Catherine; Wolf, Alexander; Brockmeyer, Andreas; Janning, Petra; Huebel, Katja; Waldmann, Herbert; Reubold, Thomas F.; Eschenburg, Susanne; Rai, Amrita; Manstein, Dietmar J.; Kaiser, Markus [Angewandte Chemie - International Edition, 2009, vol. 48, # 39, p. 7240 - 7245][Angewandte Chemie, 2009, vol. 121, # 39, p. 7376 - 7381]

22
[ 1193687-22-7 ]
[ 359860-27-8 ]
[ 1193687-01-2 ]

Yield	Reaction Conditions	Operation in experiment
42 mg	Stage #1: 3-((S,Z)-1-ethyl-4-(1-hydroxyhexadecylidene)-3,5-dioxopyrrolidin-2-yl)propanoic acid With benzotriazol-1-ol In tetrahydrofuran; dichloromethane at 0℃; for 0.166667h; Stage #2: N-(2-(2-(2-(2-amidoethoxy)ethoxy)ethoxy)ethoxy)biotinamide With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran; dichloromethane at 0 - 20℃;

Reference： [1]Knoth, Tanja; Warburg, Karin; Katzka, Catherine; Wolf, Alexander; Brockmeyer, Andreas; Janning, Petra; Huebel, Katja; Waldmann, Herbert; Reubold, Thomas F.; Eschenburg, Susanne; Rai, Amrita; Manstein, Dietmar J.; Kaiser, Markus [Angewandte Chemie - International Edition, 2009, vol. 48, # 39, p. 7240 - 7245][Angewandte Chemie, 2009, vol. 121, # 39, p. 7376 - 7381]

23
FK₅₀₆-NHS [ No CAS ]
[ 359860-27-8 ]
C₆₄H₁₀₃N₅O₁₈S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	In water; acetonitrile at 20℃; for 18h;

Reference： [1]Location in patent: experimental part Piggott, Andrew M.; Kriegel, Alison M.; Willows, Robert D.; Karuso, Peter [Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 19, p. 6841 - 6850]

24
[ 38862-24-7 ]
[ 359860-27-8 ]
[ 1192706-75-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 6841 - 6850

25
[ 359860-27-8 ]
[ 875770-34-6 ]

Yield	Reaction Conditions	Operation in experiment
62%	With triflic azide; copper(II) sulfate; triethylamine In methanol; dichloromethane; water at 0 - 25℃;

Reference： [1]Yun, Wang; Shougang, Hu; Fast, Walter [Journal of the American Chemical Society, 2009, vol. 131, # 42, p. 15096 - 15097]

26
5,8,11,14,17,20,23,26-octaoxa-2-azanonacosanedioic acid, 1-(9H-fluoren-9-ylmethyl) ester [ No CAS ]
[ 359860-27-8 ]
N-Fmoc-amino-dPEG₈-biotin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 48h;

Reference： [1]Ishihara, Yuuki; Miyazaki, Keisuke; Yamashita, Shuji; Hirama, Masahiro [Chemistry Letters, 2009, vol. 38, # 9, p. 886 - 887]

27
(1R,8S,9ξ)-bicyclo[6.1.0]non-4-yn-9-ylmethyl (4-nitrophenyl) carbonate [ No CAS ]
[ 359860-27-8 ]
[ 1263166-92-2 ]

Yield	Reaction Conditions	Operation in experiment
69%	With triethylamine In N,N-dimethyl-formamide at 20℃; for 2h; Inert atmosphere;
69%	In dichloromethane	3 Example 3: Bicyclo[6.1.0]non-4-yne (BCN) Conjugatesendo -IIa.6 : x = 2, R = Alexa Fluor 555 BCN conjugated to biotin ( Ila.4 )The alcohol moiety of endo-ll&. l was converted into a p-nitrophenyl (pNP) carbonate as in IIa.3. Subsequent reaction with biotin-(POE)3-NH2 led to BCN-biotin conjugate IIa.4 (69% yield).

Reference： [1]Dommerholt, Jan; Schmidt, Samuel; Temming, Rinske; Hendriks, Linda J. A.; Rutjes, Floris P. J. T.; Van Hest, Jan C. M.; Lefeber, Dirk J.; Friedl, Peter; Van Delft, Floris L. [Angewandte Chemie - International Edition, 2010, vol. 49, # 49, p. 9422 - 9425]
[2]Current Patent Assignee: SYNAFFIX BV - WO2011/136645, 2011, A1 Location in patent: Page/Page column 34

28
(9Z,11E)-13-hydroperoxyoctadeca-9,11-dienoic acid [ No CAS ]
[ 359860-27-8 ]
13-HPODE-biotin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 1h;

Reference： [1]Location in patent: experimental part Slade, Peter G.; Williams, Michelle V.; Brahmbhatt, Viral; Dash, Ajit; Wishnok, John S.; Tannenbaum, Steven R. [Chemical Research in Toxicology, 2010, vol. 23, # 3, p. 557 - 567]

29
[ 1240419-78-6 ]
[ 359860-27-8 ]
[ 1301630-38-5 ]

Yield	Reaction Conditions	Operation in experiment
16%	In N,N-dimethyl-formamide at 20℃; for 24h;	6.2.6. PU-H71-biotin (7) Compound 2 (4.2 mg, 0.0086 mmol) and EZ-Link Amine-PEO3-Biotin (5.4 mg, 0.0129 mmol) in DMF (0.2 mL) was stirred at rt for 24 h. The reaction mixture was concentrated and the residue chromatographed [CHCl3/MeOH-NH3 (7 N), 5:1] to give 1.1 mg (16%) of 7. 1H NMR (CDCl3) δ 8.30 (s, 1H), 8.10 (s, 1H), 7.31 (s, 1H), 6.87 (s, 1H), 6.73 (br s, 1H), 6.36 (br s, 1H), 6.16 (br s, 2H), 6.00 (s, 2H), 4.52 (m, 1H), 4.28-4.37 (m, 3H), 3.58-3.77 (m, 10H), 3.55 (m, 2H), 3.43 (m, 2H), 3.16 (m, 1H), 2.92 (m, 1H), 2.80 (m, 2H), 2.72 (m, 1H), 2.66 (m, 2H), 2.17 (t, J = 7.0 Hz, 2H), 2.04 (m, 2H), 1.35-1.80 (m, 6H); MS (ESI): m/z 872.2 [M+H]+.
16%	In N,N-dimethyl-formamide at 20℃; for 24h;	PU-H71-biotin PU-H71-biotin. 6 (4.2 mg, 0.0086 mmol) and EZ-Link Amine-PEO3-Biotin (5.4 mg, 0.0129 mmol) in DMF (0.2 mL) was stirred at rt for 24 h. The reaction mixture was concentrated and the residue chromatographed (CHCl3:MeOH-NH3 (7N), 5:1) to give 1.1 mg (16%) of PU-H71-biotin. 1H NMR (CDCl3) δ 8.30 (s, 1H), 8.10 (s, 1H), 7.31 (s, 1H), 6.87 (s, 1H), 6.73 (br s, 1H), 6.36 (br s, 1H), 6.16 (br s, 2H), 6.00 (s, 2H), 4.52 (m, 1H), 4.28-4.37 (m, 3H), 3.58-3.77 (m, 10H), 3.55 (m, 2H), 3.43 (m, 2H), 3.16 (m, 1H), 2.92 (m, 1H), 2.80 (m, 2H), 2.72 (m, 1H), 2.66 (m, 2H), 2.17 (t, J = 7.0 Hz, 2H), 2.04 (m, 2H), 1.35-1.80 (m, 6H); MS (ESI): m/z 872.2 [M+H]+/

Reference： [1]Location in patent: experimental part Taldone, Tony; Zatorska, Danuta; Patel, Pallav D.; Zong, Hongliang; Rodina, Anna; Ahn, James H.; Moulick, Kamalika; Guzman, Monica L.; Chiosis, Gabriela [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 8, p. 2603 - 2614]
[2]Current Patent Assignee: CORNELL UNIVERSITY; MEMORIAL SLOAN-KETTERING CANCER CENTER - EP3208615, 2017, A2 Location in patent: Paragraph 0375

30
triethylammonium P₁-7-methylguanosine 5'-P₃-{2',3'-O-[1-(2-carboxyethyl) 5'-triphosphate [ No CAS ]
[ 359860-27-8 ]
C₄₄H₆₈N₁₄O₂₄P₃S⁽¹⁺⁾ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
26%	Stage #1: triethylammonium P₁-7-methylguanosine 5'-P₃-{2',3'-O-[1-(2-carboxyethyl) 5'-triphosphate With 1-hydroxy-pyrrolidine-2,5-dione; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride at 20℃; for 0.333333h; aq. buffer; Stage #2: N-(2-(2-(2-(2-amidoethoxy)ethoxy)ethoxy)ethoxy)biotinamide at 20℃; for 4.5h; aq. buffer;

Reference： [1]Location in patent: experimental part Jankowska-Anyszka, Marzena; Piecyk, Karolina; Samonina-Kosicka, Jelena [Organic and Biomolecular Chemistry, 2011, vol. 9, # 15, p. 5564 - 5572]

31
P₁-N₂,N₂,7-trimethylguanosine 5'-P₃-{2',3'-O-[1-(2-carboxyethyl) 5'-triphosphate triethylammonium salt [ No CAS ]
[ 359860-27-8 ]
C₄₆H₇₂N₁₄O₂₄P₃S⁽¹⁺⁾ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
12%	Stage #1: P₁-N₂,N₂,7-trimethylguanosine 5'-P₃-{2',3'-O-[1-(2-carboxyethyl) 5'-triphosphate triethylammonium salt With 1-hydroxy-pyrrolidine-2,5-dione; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride at 20℃; for 0.333333h; aq. buffer; Stage #2: N-(2-(2-(2-(2-amidoethoxy)ethoxy)ethoxy)ethoxy)biotinamide at 20℃; for 4.5h; aq. buffer;

Reference： [1]Location in patent: experimental part Jankowska-Anyszka, Marzena; Piecyk, Karolina; Samonina-Kosicka, Jelena [Organic and Biomolecular Chemistry, 2011, vol. 9, # 15, p. 5564 - 5572]

32
C₁₉H₁₆N₆O₅ [ No CAS ]
[ 359860-27-8 ]
[ 1339202-33-3 ]

Yield	Reaction Conditions	Operation in experiment
62 mg	In N,N-dimethyl-formamide at 20℃; for 12h; Inert atmosphere;

Reference： [1]Yang, Peng-Yu; Liu, Kai; Zhang, Chongjing; Chen, Grace Y. J.; Shen, Yuan; Ngai, Mun Hong; Lear, Martin J.; Yao, Shao Q. [Chemistry - An Asian Journal, 2011, vol. 6, # 10, p. 2762 - 2775]

33
[ 359860-27-8 ]
[ 1428649-11-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triethylamine / N,N-dimethyl-formamide / 20 °C 2: pyridine hydrofluoride / tetrahydrofuran / 0 - 20 °C

Reference： [1]Mizuhara, Tsukasa; Oishi, Shinya; Ohno, Hiroaki; Shimura, Kazuya; Matsuoka, Masao; Fujii, Nobutaka [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 7, p. 2079 - 2087]

34
[ 359860-27-8 ]
[ 1428649-12-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: triethylamine / N,N-dimethyl-formamide / 20 °C 2: pyridine hydrofluoride / tetrahydrofuran / 0 - 20 °C 3: pyridine / dichloromethane / 1 h / Reflux

Reference： [1]Mizuhara, Tsukasa; Oishi, Shinya; Ohno, Hiroaki; Shimura, Kazuya; Matsuoka, Masao; Fujii, Nobutaka [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 7, p. 2079 - 2087]

35
[ 359860-27-8 ]
[ 1428649-13-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: triethylamine / N,N-dimethyl-formamide / 20 °C 2: pyridine hydrofluoride / tetrahydrofuran / 0 - 20 °C 3: pyridine / dichloromethane / 1 h / Reflux 4: triethylamine / N,N-dimethyl-formamide / 1 h / 20 °C

Reference： [1]Mizuhara, Tsukasa; Oishi, Shinya; Ohno, Hiroaki; Shimura, Kazuya; Matsuoka, Masao; Fujii, Nobutaka [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 7, p. 2079 - 2087]

36
C₄₀H₃₂N₄O₇S [ No CAS ]
[ 359860-27-8 ]
[ 1428648-98-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: triethylamine / N,N-dimethyl-formamide / 20 - 40 °C 2.1: trifluoroacetic acid / chloroform / 4 h / 20 °C / Molecular sieve 2.2: 0 °C / pH 8 - 9 / Molecular sieve

Reference： [1]Mizuhara, Tsukasa; Oishi, Shinya; Ohno, Hiroaki; Shimura, Kazuya; Matsuoka, Masao; Fujii, Nobutaka [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 7, p. 2079 - 2087]

37
C₄₀H₃₂N₄O₇S [ No CAS ]
[ 359860-27-8 ]
[ 1428649-06-2 ]

Yield	Reaction Conditions	Operation in experiment
90.6 mg	With triethylamine In N,N-dimethyl-formamide at 20 - 40℃;	4.1.7 4-(4-{6-[(4-Methoxybenzyl)imino]-2,3,4,6-tetrahydrobenzo[e]pyrimido[1,2-c][1,3]thiazin-9-yl}benzoyl)benzyl {13-oxo-17-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]-3,6,9-trioxa-12-azaheptadecyl}carbamate (17) To a solution of 13 (157.2 mg, 0.20 mmol) in THF (2.0 mL) was added TBAF in THF (1 M, 0.50 mL, 0.50 mmol). After being stirred at rt overnight, the reaction mixture was quenched with satd NH4Cl. The whole was extracted with CHCl3 and dried over MgSO4. After concentration, the residue was subjected to flash column chromatography over aluminum oxide with n-hexane/EtOAc (5:1-0:1) to give the desilylated compound. To a solution of the resulting compound in CH2Cl2 (6.0 mL) were added p-nitrophenyl chloroformate (60.5 mg, 0.30 mmol) and pyridine (64.6 μL, 0.8 mmol). After being stirred under reflux for 1 h, additional p-nitrophenyl chloroformate (12.0 mg, 0.06 mmol) was added. After being stirred under reflux for additional 30 min, the reaction mixture was washed with brine, and dried over MgSO4. After concentration, the solution of resulting residue (crude 16) in DMF (2.0 mL) was added to the solution of 15 (ca. 0.26 mmol) and Et3N (86.7 μL) in DMF (3.0 mL). After being stirred at rt for 8 h, the reaction mixture was stirred at 40 °C overnight. After concentration, the residue was purified by flash column chromatography over aluminum oxide with CHCl3/MeOH (1:0-95:5) followed by flash column chromatography over silica gel with CHCl3/MeOH (1:0-9:1) to give the title compound 17 as pale yellow amorphous (90.6 mg, 46%): IR (neat) cm-1: 1699 (C=O), 1656 (C=O), 1607 (C=N), 1511 (C=N); 1H NMR (500 MHz, CDCl3) δ: 1.39-1.45 (m, 2H, CH2), 1.57-1.74 (m, 4H, 2 × CH2), 2.03-2.08 (m, 2H, CH2), 2.20 (t, J = 6.9 Hz, 2H, CH2), 2.70 (d, J = 12.6 Hz, 1H, CH), 2.87 (dd, J = 12.6, 4.6 Hz, 1H, CH), 3.12 (d, J = 11.7, 4.6 Hz, 1H, CH), 3.40-3.43 (m, 4H, 2 × CH2), 3.54-3.71 (m, 14H, 7 × CH2), 3.77 (s, 3H, CH3), 3.88 (t, J = 6.0 Hz, 2H, CH2), 4.19 (s, 2H, CH2), 4.26-4.29 (m, 1H, CH), 4.45-4.47 (m, 1H, CH), 5.17 (s, 1H, NH), 5.20 (s, 2H, CH2), 5.65 (s, 1H, NH), 6.07 (s, 1H, NH), 6.48 (s, 1H, NH), 6.84 (d, J = 8.0 Hz, 2H, Ar), 7.26-7.28 (m, 2H, Ar), 7.44-7.62 (m, 7H, Ar), 7.81 (d, = 8.0 Hz, 2H, Ar), 7.85 (d, J = 8.0 Hz, 2H, Ar); 13C NMR (125 MHz, CDCl3) δ: 19.8, 25.5, 28.0, 28.1, 35.9, 39.0, 39.1, 40.4, 40.9, 44.3, 47.7, 55.2, 55.5, 60.1, 61.7, 65.8, 69.9, 69.9, 70.0, 70.2, 70.3 (2C), 112.2, 114.0 (2C), 125.7, 127.1 (2C), 127.4 (2C), 127.6, 128.6, 129.5, 130.2 (2C), 130.3 (2C), 130.6 (2C), 135.0, 136.5, 136.7, 137.1, 141.4, 142.0, 143.7, 148.2, 156.3, 158.9, 163.9, 173.2, 195.7; HRMS (FAB): m/z calcd for C52H62N7O9S2 [M+H]+ 992.4050; found: 992.4050.

Reference： [1]Mizuhara, Tsukasa; Oishi, Shinya; Ohno, Hiroaki; Shimura, Kazuya; Matsuoka, Masao; Fujii, Nobutaka [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 7, p. 2079 - 2087]

38
[ 1428649-09-5 ]
[ 359860-27-8 ]
[ 1428649-10-8 ]

Yield	Reaction Conditions	Operation in experiment
100%	With triethylamine In N,N-dimethyl-formamide at 20℃;	4.1.11 4-[4-(tert-Butyldiphenylsilyloxymethyl)benzoyl]benzyl {13-oxo-17-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]-3,6,9-trioxa-12-azaheptadecyl}carbamate (23) To a solution of 2120 (240.3 mg, 0.50 mmol) in CH2Cl2 (15.0 mL) were added p-nitrophenyl chloroformate (151.2 mg, 0.75 mmol) and pyridine (161.4 μL, 2.00 mmol). After being stirred under reflux for 1 h, the reaction mixture was washed with brine, and dried over MgSO4. After concentration, the solution of the resulting residue in DMF (7.5 mL) was added to a mixture of 15 (ca. 0.20 mmol) and Et3N (216.8 μL) in DMF (5.0 mL). After being stirred at rt overnight, the mixture was concentrated. The residue was purified by flash column chromatography over silica gel with CHCl3/MeOH (1:0-95:5) to give the title compound 23 as colorless amorphous (471.5 mg, quant.): IR (neat) cm-1: 1700 (C=O), 1656 (C=O), 1609 (C=O); 1H NMR (400 MHz, CDCl3) δ: 1.12 (s, 9H, 3 × CH3), 1.39-1.46 (m, 2H, CH2), 1.61-1.76 (m, 4H, 2 × CH2), 2.19-2.23 (m, 2H, CH2), 2.69-2.76 (m, 1H, CH), 2.85-2.90 (m, 1H, CH), 3.09-3.15 (m, 1H, CH), 3.39-3.43 (m, 4H, 2 × CH2), 3.54-3.66 (m, 12H, 6 × CH2), 4.26-4.33 (m, 1H, CH), 4.45-4.51 (m, 1H, CH), 4.85 (s, 2H, CH2), 5.19 (s, 2H, CH2), 5.54 (br s, 1H, NH), 5.68 (br s, 1H, NH), 6.55 (br s, 1H, NH), 6.72 (br s, 1H, NH), 7.36-7.48 (m, 10H, Ar), 7.69 (d, J = 7.6 Hz, 2H, Ar), 7.70 (d, J = 7.6 Hz, 2H, Ar), 7.77 (d, J = 5.5 Hz, 2H, Ar), 7.79 (d, J = 5.5 Hz, 2H, Ar); 13C NMR (100 MHz, CDCl3) δ: 19.3, 25.5, 26.8 (3C), 28.1, 28.2, 35.9, 39.1, 40.5, 40.9, 55.5, 60.1, 61.7, 65.1, 65.8, 69.9, 70.0, 70.0, 70.2, 70.4 (2C), 125.6 (2C), 127.4 (2C), 127.8 (4C), 129.8 (2C), 130.1 (2C), 130.2 (2C), 133.2 (2C), 135.5 (4C), 136.1, 137.4, 141.2, 146.0, 156.3 163.9, 173.2, 196.0; HRMS (FAB): m/z calcd for C50H65N4O9SSi [M+H]+ 925.4242; found: 925.4246.

Reference： [1]Mizuhara, Tsukasa; Oishi, Shinya; Ohno, Hiroaki; Shimura, Kazuya; Matsuoka, Masao; Fujii, Nobutaka [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 7, p. 2079 - 2087]

39
[ 1027338-09-5 ]
[ 359860-27-8 ]
[ 1027338-10-8 ]

Yield	Reaction Conditions	Operation in experiment
20%	With triethylamine In N,N-dimethyl-formamide at 20℃; Inert atmosphere;

Reference： [1]Borcard, Françoise; Kong, Phally; Journot, Céline; Staedler, Davide; Sturzenegger, Philip N.; Juillerat, Franziska Krauss; Gonzenbach, Urs T.; Juillerat-Jeanneret, Lucienne; Gerber-Lemaire, Sandrine [Chimia, 2013, vol. 67, # 4, p. 213 - 217]

40
[ 1426545-40-5 ]
[ 359860-27-8 ]
2,3,5,6-tetrafluoro-N-(13-oxo-17-(2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)-3,6,9-trioxa-12-azaheptadecyl)-4-(3-(4-(trifluoromethylthio)phenyl)ureido)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	Stage #1: 2,3,5,6-tetrafluoro-4-(3-(4-(trifluoromethylthio)phenyl)ureido)benzoic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide for 0.166667h; Stage #2: N-(2-(2-(2-(2-amidoethoxy)ethoxy)ethoxy)ethoxy)biotinamide In N,N-dimethyl-formamide at 25℃; for 12h;

Reference： [1]Sviripa, Vitaliy; Conroy, Michael D.; Zhang, Wen; Liu, Alice; Watt, David S. [Turkish Journal of Chemistry, 2013, vol. 37, # 4, p. 473 - 479]

41
C₅₇H₆₆N₆O₅S [ No CAS ]
[ 359860-27-8 ]
C₇₅H₉₈N₁₀O₉S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	With 1-hydroxy-pyrrolidine-2,5-dione; triethylamine; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 20℃; for 10h; Darkness;

Reference： [1]Menendez, Guillermo O.; Lopez, Cecilia Samaniego; Jares-Erijman, Elizabeth A.; Spagnuolo, Carla C. [Photochemistry and Photobiology, 2013, vol. 89, # 6, p. 1354 - 1361]

42
[ 359860-27-8 ]
[ 1613697-52-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 48 h / 25 °C / Darkness 2: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 16 h / 25 - 40 °C

Reference： [1]Vineberg, Jacob G.; Zuniga, Edison S.; Kamath, Anushree; Chen, Ying-Jen; Seitz, Joshua D.; Ojima, Iwao [Journal of Medicinal Chemistry, 2014, vol. 57, # 13, p. 5777 - 5791]

43
[ 359860-27-8 ]
[ 1613697-53-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 48 h / 25 °C / Darkness 2: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 16 h / 25 - 40 °C 3: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 12 h / 50 °C

Reference： [1]Vineberg, Jacob G.; Zuniga, Edison S.; Kamath, Anushree; Chen, Ying-Jen; Seitz, Joshua D.; Ojima, Iwao [Journal of Medicinal Chemistry, 2014, vol. 57, # 13, p. 5777 - 5791]

44
[ 359860-27-8 ]
[ 1613697-55-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 48 h / 25 °C / Darkness 2: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 16 h / 25 - 40 °C 3: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 12 h / 50 °C 4: dichloromethane / 25 °C

Reference： [1]Vineberg, Jacob G.; Zuniga, Edison S.; Kamath, Anushree; Chen, Ying-Jen; Seitz, Joshua D.; Ojima, Iwao [Journal of Medicinal Chemistry, 2014, vol. 57, # 13, p. 5777 - 5791]

45
[ 359860-27-8 ]
[ 1613697-57-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 48 h / 25 °C / Darkness 2: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 16 h / 25 - 40 °C 3: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 12 h / 50 °C 4: dichloromethane / 25 °C 5: pyridine / dichloromethane / 10 h / 25 °C

Reference： [1]Vineberg, Jacob G.; Zuniga, Edison S.; Kamath, Anushree; Chen, Ying-Jen; Seitz, Joshua D.; Ojima, Iwao [Journal of Medicinal Chemistry, 2014, vol. 57, # 13, p. 5777 - 5791]

46
[ 1173-43-9 ]
[ 359860-27-8 ]
C₃₉H₄₅N₅O₁₀S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 25℃; for 48h; Darkness;

Reference： [1]Vineberg, Jacob G.; Zuniga, Edison S.; Kamath, Anushree; Chen, Ying-Jen; Seitz, Joshua D.; Ojima, Iwao [Journal of Medicinal Chemistry, 2014, vol. 57, # 13, p. 5777 - 5791]

47
[ 55750-63-5 ]
[ 359860-27-8 ]
C₂₈H₄₅N₅O₈S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%	In N,N-dimethyl-formamide at 20℃; for 3h; Inert atmosphere;

Reference： [1]Asano, Shigehiro; Patterson, James T.; Gaj, Thomas; Barbas, Carlos F. [Angewandte Chemie - International Edition, 2014, vol. 53, # 44, p. 11783 - 11786]

48
C₅₆H₆₅F₆NO₁₉S₂ [ No CAS ]
[ 359860-27-8 ]
C₇₄H₉₇F₆N₅O₂₃S₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 12h;	4.7.3 Biotin-PEG-(SS-linker)-SB-T-12822-5 [BLT-S-F₆] (2) To a solution of 26 (0.189 g, 0.151 mmol), 27 (0.094 g, 0.226 mmol), and DMAP (0.019 g, 0.151 mmol) in CH2Cl2 (10mL) was added EDC·HCl (0.035g, 0.181mmol), and the mixture was allowed to react for 12h at room temperature with stirring. The reaction mixture was directly concentrated in vacuo to give a yellow oil. Purification of the crude produt by column chromatography on silica gel with 8% CH3OH in CH2Cl2 as eluent gave BLT-S-F6 (2) as a white solid (0.165g, 80%): mp 104-106°C; 1H NMR (500 MHz, CDCl3): δ 1.02 (t, J=8.0Hz, 2H), 1.18 (s, 3H), 1.28 (s, 3H), 1.30 (d, J=6.8Hz, 3H), 1.37 (s, 9H), 1.48 (m, 4H), 1.73 (m, 9H), 1.91 (m, 4H), 1.92 (s, 3H), 2.34 (m, 4H), 2.35 (s, 3H), 2.36 (m, 1H), 2.48 (t, J=7.5Hz, 2H), 2.55 (m, 1H), 2.75 (d, J=12.5Hz, 1H), 2.92 (m, 1H), 2.93 (dd, J=4.5, 12.5Hz, 1H), 3.20 (m, 2H), 3.46 (m, 4H), 3.59 (t, J=5.0Hz, 2H), 3.66 (m, 10H), 3.83 (d, J=7.0Hz, 1H), 4.01 (m, 2H), 4.09 (dd, J=3.5, 6.5Hz, 1H), 4.19 (d, J=8.5Hz, 1H), 4.35 (m, 5H), 4.54 (m, 1H), 4.94 (m, 1H), 4.99 (d, J=9.0Hz, 1H), 5.20 (s, 2H), 5.39 (s, 1H), 5.57 (t, J=11.0Hz, 1H), 5.66 (d, J=7.0Hz, 1H), 5.78 (s, 1H), 6.17 (s, 1H), 6.20 (t, J=8.0Hz, 1H), 6.33 (s, 1H), 6.51 (m, 1H), 6.75 (bt, 1H), 7.28 (m, 2H), 7.35 (m, 1H), 7.48 (d, J=8.0Hz, 1H), 7.59 (t, J=7.5Hz, 1H), 7.83 (d, J=7.5Hz, 1H), 8.03 (s, 1H), 8.08 (d, J=8.0Hz, 1H); 13C NMR (125MHz, CDCl3): δ 9.21, 9.39, 9.62, 13.04, 14.74, 20.62, 20.97, 22.03, 22.52, 25.14, 22.52, 25.14, 25.54, 26.59, 27.96, 28.05, 28.12, 28.27, 28.31, 29.73, 31.31, 33.42, 33.50, 35.32, 35.64, 35.84, 38.44, 39.10, 30.15, 40.52, 42.86, 43.18, 45.85, 46.33, 47.85, 53.46, 55.32, 55.32, 55.50, 58.38, 60.19, 61.78, 69.41, 69.94, 70.00, 70.08, 70.36, 71.92, 72.47, 75.30, 75.71, 76.25, 79.20, 81.08, 81.52, 84.53, 122.29, 126.18. 127.79, 128.54, 130.40, 130.50, 130.55, 130.86, 131.26, 132.64, 132.92, 137.59, 142.29, 149.30, 153.96, 154.82, 163.42, 163.64, 165.59, 166.44, 170.00, 172.43, 173.33, 173.33, 174.04, 174.85, 203.75; 19F NMR (470MHz, CDCl3): δ -57.92 (s, 3F), -73.11 (d, J=7.5Hz, 3F). HRMS (TOF): Calcd. for C74H98F6N5O23S3+: 1634.5713; Found: 1634.5698 (Δ=-0.9ppm).

Reference： [1]Seitz, Joshua D.; Vineberg, Jacob G.; Wei, Longfei; Khan, Jonathan F.; Lichtenthal, Brendan; Lin, Chi-Feng; Ojima, Iwao [Journal of Fluorine Chemistry, 2015, vol. 171, p. 148 - 161]

49
[ 112-60-7 ]
[ 359860-27-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: methanesulfonyl chloride; triethylamine / tetrahydrofuran / 4 h / 0 - 20 °C 1.2: 19 h / pH 8 / Reflux 2.1: phosphoric acid; triphenylphosphine / diethyl ether / 22 h / 20 °C 3.1: dichloromethane / 20 °C 4.1: hydrogen; 5%-palladium/activated carbon / ethanol / 12 h / 20 °C

Reference： [1]Current Patent Assignee: STATE UNIVERSITY OF NEW YORK - WO2015/38493, 2015, A1

50
[ 101187-39-7 ]
[ 359860-27-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: phosphoric acid; triphenylphosphine / diethyl ether / 22 h / 20 °C 2: dichloromethane / 20 °C 3: hydrogen; 5%-palladium/activated carbon / ethanol / 12 h / 20 °C
	Multi-step reaction with 2 steps 1: hydrogenchloride; triphenylphosphine / water; diethyl ether / 12 h / 20 °C 2: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 12 h / 20 °C

Reference： [1]Current Patent Assignee: STATE UNIVERSITY OF NEW YORK - WO2015/38493, 2015, A1
[2]Current Patent Assignee: UNIVERSITY OF CALIFORNIA - US9889182, 2018, B2

51
[ 35013-72-0 ]
[ 134179-38-7 ]
[ 359860-27-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: dichloromethane / 20 °C 2: hydrogen; 5%-palladium/activated carbon / ethanol / 12 h / 20 °C

Reference： [1]Current Patent Assignee: STATE UNIVERSITY OF NEW YORK - WO2015/38493, 2015, A1

52
[ 58-85-5 ]
[ 359860-27-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: diisopropyl-carbodiimide / N,N-dimethyl-formamide / 45 °C 2: dichloromethane / 20 °C 3: hydrogen; 5%-palladium/activated carbon / ethanol / 12 h / 20 °C
	Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 0.5 h / 20 °C 2: trifluoroacetic acid / dichloromethane / 20 °C

Reference： [1]Current Patent Assignee: STATE UNIVERSITY OF NEW YORK - WO2015/38493, 2015, A1
[2]Han, Xin; Wang, Chao; Qin, Chong; Xiang, Weiguo; Fernandez-Salas, Ester; Yang, Chao-Yie; Wang, Mi; Zhao, Lijie; Xu, Tianfeng; Chinnaswamy, Krishnapriya; Delproposto, James; Stuckey, Jeanne; Wang, Shaomeng [Journal of Medicinal Chemistry, 2019, vol. 62, # 2, p. 941 - 964]

53
[ 1613697-49-6 ]
[ 359860-27-8 ]
C₇₆H₁₀₅N₅O₂₂S₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane at 20℃; for 16h;

Reference： [1]Current Patent Assignee: STATE UNIVERSITY OF NEW YORK - WO2015/38493, 2015, A1 Location in patent: Paragraph 0081

54
[ 444935-91-5 ]
[ 359860-27-8 ]
[ 1613697-52-1 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine at 40℃; for 16h;

Reference： [1]Current Patent Assignee: STATE UNIVERSITY OF NEW YORK - WO2015/143092, 2015, A1 Location in patent: Page/Page column 117

55
C₁₁H₁₇Cl₂N₇O₃ [ No CAS ]
[ 359860-27-8 ]
2-chloro-4-(1 1-biotinylamino-3,6,9-trioxaundecyl)amino-6-(1 1-azido-3,6,9-trioxaundecyl)amino-1,3,5-triazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
210 mg	With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 60℃;	2-Chloro-4-(1 1-biotinylamino-3,6,9-trioxaundecyl)amino-6-(1 1-azido-3,6,9-trioxaundecyl)amino-1,3,5-triazine (3’) To a 100 mL round-bottomed flaskwas added cyanuric chloride (124 mg, 0.67 mmol) dissolved in 0.02 THF (33.5 mL) under 0 °C in an ice-water bath. To this solution was slowly added 1 equivalent of 1’ (146 mg, 0.67 mmol) dissolved in 2 mL THF, followed by addition of 1.5 equivalents of DIPEA (86.6 mg, 0.67 mmol, 0.12 mL). The resulting solution was allowed to warm to room temperature and stirred for 2 hours. Then the reaction mixture was transferred to another rbf containing 1 equivalent of 2’ (280 mg, 0.67 mmol), followed by addition of 1.5 eq DIPEA (86.6 mg, 0.67 mmol, 0.12 mL). The reaction mixture was heated to 60 °C and allowed to stir overnight. Upon completion, the solvent was removed and the product was purified by silica gel column chromatography eluting 0-10 % methanol in dichloromethane to yield 3’ as a white sticky solid (210 mg, 0.28 mmol, 42 %): ‘H NMR (500 MHz, CDC13) 0.74-0.77 (m, J= 6.37 Hz, 1 H), 0.78 (t, J= 6.93 Hz, 1 H), 1.02 (d, J= 6.51 Hz, 1 H), 1.16-1.20 (m, 2 H), 1.32-1.35 (m, 3 H), 1.43-1.46 (m, 2 H), 1.54-1.59 (m, 3 H), 1.64-1.65 (m, 1 H),2.10-2.14 (m, 2 H), 2.65 (d, J= 12.67 Hz, 1 H), 2.79 (dd, Ja = 4.76 Hz, Jb = 12.74Hz, 1 H), 3.00-3.05 (m, 2 H), 3.30-3.33 (m, 3 H), 3.48-3.58 (m, 26 H), 3.58-3.68 (m, 1 H), 4.22 (m, 1 H), 4.41 (t, J= 5.53 Hz, 1 H), 6.14 (m, 1 H). ‘3C NMR (500 MHz, CDC13) 11.3, 11.9, 14.0, 17.3, 18.5, 22.5, 23.4, 25.5, 25.6, 28.1, 28.3, 28.9, 29.5, 31.4, 34.5, 35.8, 35.9, 35.9, 39.0, 40.4, 40.5, 40.6, 40.7, 41.9, 42.8, 50.6, 53.6, 55.6,56.6, 60.2, 61.7, 69.2, 69.9, 69.9541, 70.0, 70.3, 70.5, 70.5, 71.2, 164.3, 165.5, 165.6,168.1, 168.9, 169.0, 173.3, 173.4. HRMS (TOF) [M+Hf mlz calcd. for C29H51ClN,,O8S: 748.3326, found 748.3321.

Reference： [1]Current Patent Assignee: STATE UNIVERSITY OF NEW YORK - WO2015/143092, 2015, A1 Location in patent: Paragraph 0161

56
4-[3-cyano-4'-((S)-6-methoxycarbonylmethyl-2,3,9-trimethyl-6H-1-thia-5,7,8,9a-tetraazacyclopenta[e]azulen-4-yl)biphenyl-4-yloxymethyl]benzoic acid [ No CAS ]
[ 359860-27-8 ]
C₅₃H₆₁N₉O₉S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
29%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 20℃; Inert atmosphere;	[(S)-4-(3'-Cyano-4'-phenoxymethyl)-N-{2-[2-(2-{2-[5-((3aR,6S,6aS)-2-oxo-hexahydro-thieno[3,4-d]imidazol-6-yl)-pentanoylamino]-ethoxy}-ethoxy)-ethoxy]-ethyl}-biphenyl-4-yl)-2,3,9-trimethyl-6H-1-thia-5,7,8,9a-tetraazacyclopenta[e]azulen-6-yl]acetic acid methyl ester (9) Step 4: A mixture of 4-[3-Cyano-4'-((S)-6-methoxycarbonylmethyl-2,3,9-trimethyl-6H-1-thia-5,7,8,9a-tetraaza-cyclopenta[e]azulen-4-yl)-biphenyl-4-yloxymethyl]-benzoic acid (13) (100 mg, 0.158 mmol), N-Biotinyl-3,6,9-trioxaundecane-1,11-diamine (66 mg, 0.158 mmol), 3-(Ethyliminomethyleneamino)-N,N-dimethyl-propan-1-amine;hydrochloride (36 mg, 0.19 mmol), 1-Hydroxybenzotriazole (28mg, 0.21 mmol), Et3N (0.066 mL, 0.47 mmol), and DMF (3 mL),under N2 was stirred at room temperatureforovernight. The reaction mixture was extracted with CHCl3. The combined organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and evaporated.The residue was purified by flash column chromatography(MeOH/CHCl3)to give the desired product in a yield of 29%.ESI-MS m/z: 1032(M+H) +.

Reference： [1]Endo, Junichi; Hikawa, Hidemasa; Hamada, Maiko; Ishibuchi, Seigo; Fujie, Naoto; Sugiyama, Naoki; Tanaka, Minoru; Kobayashi, Haruhito; Sugahara, Kunio; Oshita, Koichi; Iwata, Kazunori; Ooike, Shinsuke; Murata, Meguru; Sumichika, Hiroshi; Chiba, Kenji; Adachi, Kunitomo [Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 5, p. 1365 - 1370]

57
C₃₇H₂₆N₈O₂Rh⁽³⁺⁾*3Cl^(1-) [ No CAS ]
[ 359860-27-8 ]
C₅₅H₅₈N₁₂O₆RhS⁽³⁺⁾*3Cl^(1-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate In N,N-dimethyl-formamide; acetonitrile at 20℃; for 2h;

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US9279146, 2016, B2 Location in patent: Paragraph 0060-0062

58
[ 127985-74-4 ]
[ 359860-27-8 ]
C₄₂H₆₇N₉O₁₃S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In dimethyl sulfoxide at 20℃; for 3h;	2 DOTA-Bn-biotin was synthesized by dissolving Amine-PEG3-Biotin (Pierce 21347) and p-SCN-Bn-DOTA (S-2-(4-Isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-tetraacetic acid; Macocyclics B-205) in dimethyl sulfoxide(DMSO) with a 10-fold molar excess of 30 triethylamine (VWR EM-TX 1200-5). The reaction mixture was vortexed atroom temperature for 3 hours, and then purified by high performance liquid chromatography (HPLC). HPLC purificationwas performed on a C-18 reverse-phase column (Agilent Model 1100 HPLC, 1 x 25 cm, buffer A = 0.05% trifluoroaceticacid (TFA), buffer B = 0.0425% TFA in 80% acetonitrile, 2 - 100% B gradient for 98 minutes). Flow through was monitoredby absorbance detection at 280 nanometers. Fractions containing DOTA-Bn-biotin were confirmed using matrix assistedlaser desorption instrument time of flight (MALDI-TOF) mass spectrometry (Applied Biosystems Model Voyager DESTR).Chemical purity was assessed by analytical HPLC (Agilent Model 1100 HPLC, 2.1 x 150 mm, buffer A = 0.05%TFA, buffer B = 0.0425% TFA in 80% acetonitrile, 2-100% B gradient for 45 minutes). DOTA-Bn-biotin concentrationwas determined using a biotin quantitation kit (Pierce 28005) following the manufacturer’s instructions.

Reference： [1]Current Patent Assignee: MASSACHUSETTS INSTITUTE OF TECHNOLOGY - EP2403530, 2016, B1 Location in patent: Paragraph 0117

59
[ 34078-85-8 ]
[ 359860-27-8 ]
C₃₁H₄₈N₆O₉S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 2h;	ZQ(PEG)3 l3iotin ZQ NHS (45.1 mg, 0.119 mmol), biotin amine (Pierce cat 21347, 50 mg, 0.119 mmol), and DIPEA (23 uE, 0.131 mmol) were combined in DMF (2 mE) and stirred at room temp for 2 hours at which time ECMS shows predominantly product. Reaction loaded on HPEC (Sunfire 30x50 mm Sum column 15-20% gradient ACN/H20 w/0. 1% TFA 75 ml/min 1.5 ml injection, rt=2.46) to give the desired product in 43% yield. ECMS 5Q4 RXNMON_Acidic Rt=0.79 mi M+H 681.4; 1H NMR (METHANOE-d4, 400 MHz): d=7.33-7.41 (m, 4H), 7.27-7.33 (m, 1H), 5.08 (s, 2H), 4.48 (dd, J=7.8, 4.4Hz, 1H), 4.29 (dd, J=7.9, 4.5 Hz, 1H), 4.12 (m, 1H), 3.57-3.67(m, 8H), 3.49-3.57 (m, 4H), 3.34-3.43 (m, 4H), 3.15-3.23 (m,1H), 2.92 (dd, J=12.8, 5.1 Hz, 1H), 2.70 (d, J=12.8 Hz, 1H),2.26-2.36 (m, 2H), 2.21 (t, J=7.4 Hz, 2H), 2.04 (m, 1H), 1.92(m, 1H), 1.53-1.77 (m, 4H), 1.44 ppm (m, 2H).

Reference： [1]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - US9359400, 2016, B2 Location in patent: Page/Page column 89; 90

60
11-(fluoroethoxyphosphoryl)-(N-hydroxysuccinyl)undecamide [ No CAS ]
[ 359860-27-8 ]
C₃₁H₅₈FN₄O₈PS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol for 0.166667h;

Reference： [1]Pampalakis; Zingkou; Vekrellis; Sotiropoulou [Chemical Communications, 2017, vol. 53, # 22, p. 3246 - 3248]

61
2-(4-(2-(N-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)carbamimidoyl)-5-methyl-4-oxo-4,5-dihydrothieno[3,2-c]pyridin-7-yl)-2-methoxyphenoxy)acetic acid [ No CAS ]
[ 359860-27-8 ]
C₄₁H₅₇N₇O₁₁S₃*C₂HF₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30%	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide for 16h;

Reference： [1]Remillard, David; Buckley, Dennis L.; Paulk, Joshiawa; Brien, Gerard L.; Sonnett, Matthew; Seo, Hyuk-Soo; Dastjerdi, Shiva; Wühr, Martin; Dhe-Paganon, Sirano; Armstrong, Scott A.; Bradner, James E. [Angewandte Chemie - International Edition, 2017, vol. 56, # 21, p. 5738 - 5743][Angew. Chem., 2017, vol. 129, # 21, p. 5832 - 5837]

62
2,5-dioxopyrrolidin-1-yl (E)-4-((1,3-dimesityl-1,3-dihydro-2H-imidazol-2-ylidene)triaz-1-en-1-yl)benzoate [ No CAS ]
[ 359860-27-8 ]
(E)-N-(1-(4-((1,3-dimesityl-1,3-dihydro-2H-imidazol-2-ylidene)triaz-1-en-1-yl)phenyl)-1-oxo-2,6,9,12-tetraoxa-3-azatetradecan-14-yl)-5-(2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	In N,N-dimethyl-formamide at 20℃; for 10h;

Reference： [1]Addy, Partha Sarathi; Erickson, Sarah B.; Italia, James S.; Chatterjee, Abhishek [Journal of the American Chemical Society, 2017, vol. 139, # 34, p. 11670 - 11673]

63
[ 132178-37-1 ]
[ 359860-27-8 ]
C₂₃H₃₈N₄O₆S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	In acetonitrile at 20℃; for 1h;	Compound-S14 [8] To a solution of amine-Peg3-biotin (S12, purchased from Pierce) (20 mg, 0.0478 mmol) in MeCN (3 mL) was added 4-pentynoic acid N-hydroxysuccinimide ester (S13, 9.3 mg, 0.0478 mmol), and the whole was stirred at rt for 1 h. The reaction mixture was evaporated and purified with flash chromatography (CH2Cl2/MeOH = 4:1) to give desired product S14 (18.2 g, 76%). 1H NMR (400 MHz, CDCl3) δ 6.73 - 6.70 (m, 2H), 6.45 (s, 1H), 5.58 (s, 1H), 4.55 (dd, J = 8.0, J = 5.0 Hz, 1H), 4.34 (dd, J = 7.9, J = 4.5 Hz, 1H), 3.69 - 3.64 (m, 12H), 3.59 (t, 2H, J = 5.3 Hz), 3.50 - 3.44 (m, 2H), 3.20 (m, 1H), 2.96 (dd, J = 12.8, 5.0 Hz, 1H), 2.78 (t, 1H, J = 2.4 Hz), 2.57 - 2.52 (m, 2H), 2.46 - 2.42 (m, 2H), 2.22 (t, J = 7.3 Hz, 2H), 2.05 (t, J = 2.4 Hz, 1H), 1.78 - 1.65 (m, 4H), 1.51 - 1.45 (m, 2H).

Reference： [1]Nagano, Masanobu; Carrillo, Nancy; Otsubo, Nobumasa; Hakamata, Wataru; Ban, Hitoshi; Fuller, Roberta P.; Bashiruddin, Nasir K.; Barbas, Carlos F. [Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 21, p. 5952 - 5961]

64
[ 132178-37-1 ]
[ 359860-27-8 ]
C₄₉H₇₁N₉O₁₁S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: acetonitrile / 1 h / 20 °C 2: copper(ll) sulfate pentahydrate; sodium L-ascorbate; 3-[4-[[bis[[1-(3-hydroxypropyl)triazol-4-yl]methyl]amino]methyl]triazol-1-yl]propan-1-ol / water; acetonitrile / 3 h / 20 °C

Reference： [1]Nagano, Masanobu; Carrillo, Nancy; Otsubo, Nobumasa; Hakamata, Wataru; Ban, Hitoshi; Fuller, Roberta P.; Bashiruddin, Nasir K.; Barbas, Carlos F. [Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 21, p. 5952 - 5961]

65
[ 864066-74-0 ]
[ 359860-27-8 ]
biotin-PEG₃-CTP [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In dichloromethane for 48h;	In this example, Biotin-PEG3-CTP was used as a chain transfer agent (CTA) for RAFT polymerization. 23 Biotin-PEG3-CTP was synthesized by reacting 24 4-Cyano-4-(phenylcarbonothioylthio)pentanoic acid N-succinimidyl ester (NHS-CTP, 2 eq.) with 25 Amine-PEG3-Biotin (EZ-Link, ThermoFisher Scientific, 1 eq. added in 3 portions) in 26 DIPEA (4 eq.) and DCM for 48 h before purification by flash column chromatography and RP-HPLC. CTA (dissolved in 27 ethanol), VA-044 initiator, 28 HPMA, and 29 APMA were dissolved in 9:1 (v/v) 1 M acetate buffer (pH 5.1): ethanol at the [CTA]:[I]:[HPMA]:[APMA] ratio of 1:0.5:390:10 and the final monomer concentration of 1 M. The relative ratio of [CTA]:[HPMA]:[APMA] may be varied to obtain polymers with different degree of polymerization and functionalizable monomer content for peptide grafting. The reaction solution in a flask was sealed with a rubber septum and purged with nitrogen for 15 min before being immerged in an oil bath preheated to 44° C. The polymerization was stopped after 24 h by air exposure and then precipitated in cold acetone twice. Endcapping of polymer was performed by reacting the polymer with excess of VA-044 (40 eq.) in 1 M acetate buffer (pH 5.1) at 44° C. for 4 h with subsequent purification by dialysis against water and lyophilization. Conversion of amine groups on APMA to azide groups was performed via diazo-transfer reaction using imidazole-1-sulfonyl azide hydrochloride (3 APMA eq.) in DIPEA (9 APMA eq.) and DMSO with CuSO4.5H2O (0.01 APMA eq.) as a catalyst. The reaction was stirred at room temperature for 24 h before dialysis against water and lyophilization to obtain Biotin-p(HPMA-co-AziMA). Alternatively, azidopropyl methacrylamide monomer may be synthesized and directly copolymerized with HPMA to obtain the same product.

Reference： [1]Current Patent Assignee: UNIVERSITY OF WASHINGTON - US2017/246311, 2017, A1 Location in patent: Paragraph 0212

66
[ 638-56-2 ]
[ 359860-27-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: sodium azide / N,N-dimethyl-formamide / 4 h / 60 °C 2: hydrogenchloride; triphenylphosphine / water; diethyl ether / 12 h / 20 °C 3: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 12 h / 20 °C

Reference： [1]Current Patent Assignee: UNIVERSITY OF CALIFORNIA - US9889182, 2018, B2

67
[ 929-75-9 ]
[ 35013-72-0 ]
[ 359860-27-8 ]

Yield	Reaction Conditions	Operation in experiment
98%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 12h;	Compound 7. N,N-dimethylformamide (400 muL), Biotin NHS (72 mg, 0.211 mmol), and N,N-diisopropylethylamine (33 mg, 0.25 mmol) were added to 15 (42 mg, 0.19 mmol) for 12 h at RT. The reaction was concentrated under reduced pressure and purified on silica gel using flash chromatography (2-5% methanol in CH2Cl2) to afford the product as an oil (84 mg, 0.189 mmol, 98% yield).

Reference： [1]Patent: US9889182,2018,B2 .Location in patent: Page/Page column 93; 95; 96; 97; 98

68
C₉₅H₁₆₁N₁₉O₃₇ [ No CAS ]
[ 359860-27-8 ]
C₁₁₃H₁₉₃N₂₅O₄₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With copper(l) iodide; caesium carbonate In dichloromethane; acetonitrile at 20℃; for 12h;	21 Synthesis of Nomomeric and Dimeric Guanidinoneomycin Conjugates Compound 1. 12 (25 mg, 12 mmol) and 7 (11 mg, 24 mmol) were dissolved in 23 CH2Cl2 (800 μl) and treated with 181 Cs2CO3 (400 μg, 1.2 mmol) and a 0.04 M solution of 182 CuI in 62 acetonitrile (40 μl) for 12 h at RT. The reaction was then diluted into 22 ethyl acetate (10 mL) and washed with water (3×10 mL), brine (10 mL), and dried over sodium sulfate. The combined organic layers were concentrated under reduced pressure and used without further purification. The crude product was dissolved in CH2Cl2 (2 mL) and treated with 72 triisopropylsilane (20 μL, mmol) and 25 trifluoroacetic acid (2 mL) for 1 h at RT. The reaction was diluted into 73 toluene (5 mL) and concentrated under reduced pressure. The solid was then dissolved in 26 water (5 mL) and washed with CH2Cl2 (3×5 mL). The aqueous phase was reduced to a solid under reduced pressure and purified on a C-18 reverse phase HPLC column using a gradient of 5-20% acetonitrile (0.1% TFA) in water (0.1% TFA) over 20 minutes (3 mL/min) The compound eluted as a TFA salt at 16.6 min (13 mg, 11 μmol, 88% yield).

Reference： [1]Current Patent Assignee: UNIVERSITY OF CALIFORNIA - US9889182, 2018, B2 Location in patent: Page/Page column 101; 103; 104; 107; 108

69
C₈₄H₁₄₂N₁₆O₃₄ [ No CAS ]
[ 359860-27-8 ]
C₁₀₂H₁₇₄N₂₂O₃₉S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With copper(l) iodide; caesium carbonate In dichloromethane at 20℃; for 12h;	22 Synthesis of Monomeric and Dimeric Guanidinoparomomycin Conjugates Compound 26. 25 (65 mg, 0.054 mmol) was dissolved in 23 CH2Cl2 (3 mL), and treated with 72 triisopropylsilane (30 μL) and 25 trifluoroacetic acid (3 mL) for 1 h at RT. The reaction was diluted into 73 toluene (30 mL) and concentrated under reduced pressure. The solid was then dissolved in 26 water (10 mL) and washed with CH2Cl2 (3×15 mL). The aqueous phase was then reduced to a solid under reduced pressure. The crude product was dissolved in 32 methanol (500 μL) and treated with a solution of 178 N,N′-di-tertbutoxycarbonyl-N″-triflylguanidine (650 mg, 1.66 mmol) and 34 triethylamine (160 μL, 1.15 mmol) in 35 CHCl3 (2 mL) for 36 h at RT under argon. The reaction was then diluted into CH2Cl2 (15 mL), washed with water (3×10 mL), brine (10 mL), and dried over sodium sulfate. The combined organic layer were concentrated under reduced pressure and further purified by flash chromatography (2% methanol in CH2Cl2) to afford the 187 product as an off-white solid (34 mg, 0.018 mmol, 39% yield).

Reference： [1]Current Patent Assignee: UNIVERSITY OF CALIFORNIA - US9889182, 2018, B2 Location in patent: Page/Page column 108; 111;112; 113; 114

70
C₇₉H₁₃₄N₁₆O₂₉ [ No CAS ]
[ 359860-27-8 ]
C₉₇H₁₆₆N₂₂O₃₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With copper(l) iodide; caesium carbonate In dichloromethane; acetonitrile at 20℃; for 12h;	23 Synthesis of Monomeric and Dimeric Guanidinotobramycin Compound 5. 30 (28 mg, 16 μmol) and 7 (7 mg, 24 μmol) were dissolved in CH2Cl2 (600 μl) and treated with Cs2CO3 (300 mg, 1 μmol) and a 0.04 M solution of CuI in acetonitrile (40 μl) for 12 h at RT. The solvents were removed under reduced pressure and the crude product was dissolved in CH2Cl2 (4 mL) and treated with triisopropylsilane (40 μL, mmol) and trifluoroacetic acid (4 mL) for 1 h at RT. The reaction was diluted into toluene and (5 mL) and concentrated under reduced pressure. The solid was then dissolved in water (5 mL) and washed with CH2Cl2 (3×5 mL). The aqueous phase was reduced to a solid under reduced pressure and purified on a C-18 reverse phase HPLC column using a gradient of 20-40% acetonitrile (0.1% TFA) in water (0.1% TFA) over 15 minutes (3 mL/min). The compound eluted at 9.0 min (22 mg, 14 μmol, 88% yield).

Reference： [1]Current Patent Assignee: UNIVERSITY OF CALIFORNIA - US9889182, 2018, B2 Location in patent: Page/Page column 114; 115; 116; 119

71
[ 832-53-1 ]
[ 359860-27-8 ]
5-((3aS,4S,6aR)-2-oxohexahydro-1 H-thieno[3,4-d]imidazol-4-yl)-N-(2-(2-(2-(2-((pentafluorophenyl)sulfonamido)ethoxy)ethoxy)ethoxy)ethyl)pentanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 3h;

Reference： [1]Embaby, Ahmed M.; Schoffelen, Sanne; Kofoed, Christian; Meldal, Morten; Diness, Frederik [Angewandte Chemie - International Edition, 2018, vol. 57, # 27, p. 8022 - 8026][Angew. Chem., 2018, vol. 130, # 27, p. 8154 - 8158,5]

72
C₃₂H₃₂N₆O₄ [ No CAS ]
[ 359860-27-8 ]
C₄₆H₆₁N₉O₆S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	In N,N-dimethyl-formamide at 20℃; for 16h;

Reference： [1]Current Patent Assignee: BOSTON COLLEGE - US2018/360984, 2018, A1 Location in patent: Paragraph 0084

73
[ 359860-27-8 ]
C₃₁H₄₆N₆O₆S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 0.5 h / 20 °C 2: trifluoroacetic acid / dichloromethane / 20 °C

Reference： [1]Han, Xin; Wang, Chao; Qin, Chong; Xiang, Weiguo; Fernandez-Salas, Ester; Yang, Chao-Yie; Wang, Mi; Zhao, Lijie; Xu, Tianfeng; Chinnaswamy, Krishnapriya; Delproposto, James; Stuckey, Jeanne; Wang, Shaomeng [Journal of Medicinal Chemistry, 2019, vol. 62, # 2, p. 941 - 964]

74
[ 359860-27-8 ]
(2S,4R)-4-hydroxy-1-((R)-3-methyl-2-(3-methylisoxazol-5-yl)butanoyl)-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)-3,17-dioxo-21-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)-7,10,13-trioxa-4,16-diazahenicosyl)pyrrolidine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 0.5 h / 20 °C 2: trifluoroacetic acid / dichloromethane / 20 °C 3: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 0.5 h / 20 °C

Reference： [1]Han, Xin; Wang, Chao; Qin, Chong; Xiang, Weiguo; Fernandez-Salas, Ester; Yang, Chao-Yie; Wang, Mi; Zhao, Lijie; Xu, Tianfeng; Chinnaswamy, Krishnapriya; Delproposto, James; Stuckey, Jeanne; Wang, Shaomeng [Journal of Medicinal Chemistry, 2019, vol. 62, # 2, p. 941 - 964]

75
(S)-3-((tert-butoxycarbonyl)amino)-3-(4-(4-methylthiazol-5-yl)phenyl)propanoic acid [ No CAS ]
[ 359860-27-8 ]
C₃₆H₅₄N₆O₈S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 0.5h;

Reference： [1]Han, Xin; Wang, Chao; Qin, Chong; Xiang, Weiguo; Fernandez-Salas, Ester; Yang, Chao-Yie; Wang, Mi; Zhao, Lijie; Xu, Tianfeng; Chinnaswamy, Krishnapriya; Delproposto, James; Stuckey, Jeanne; Wang, Shaomeng [Journal of Medicinal Chemistry, 2019, vol. 62, # 2, p. 941 - 964]

76
C₂₇H₃₃N₅O₁₅ [ No CAS ]
[ 359860-27-8 ]
C₃₉H₆₂N₈O₁₇S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%	With triethylamine In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere;

Reference： [1]Zong, Guanghui; Hu, Zhijian; O'Keefe, Sarah; Tranter, Dale; Iannotti, Michael J.; Baron, Ludivine; Hall, Belinda; Corfield, Katherine; Paatero, Anja O.; Henderson, Mark J.; Roboti, Peristera; Zhou, Jianhong; Sun, Xianwei; Govindarajan, Mugunthan; Rohde, Jason M.; Blanchard, Nicolas; Simmonds, Rachel; Inglese, James; Du, Yuchun; Demangel, Caroline; High, Stephen; Paavilainen, Ville O.; Shi, Wei Q. [Journal of the American Chemical Society, 2019, vol. 141, # 21, p. 8450 - 8461]

77
C₂₇H₃₄N₆O₁₄ [ No CAS ]
[ 359860-27-8 ]
C₃₉H₆₃N₉O₁₆S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%	With triethylamine In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere;

Reference： [1]Zong, Guanghui; Hu, Zhijian; O'Keefe, Sarah; Tranter, Dale; Iannotti, Michael J.; Baron, Ludivine; Hall, Belinda; Corfield, Katherine; Paatero, Anja O.; Henderson, Mark J.; Roboti, Peristera; Zhou, Jianhong; Sun, Xianwei; Govindarajan, Mugunthan; Rohde, Jason M.; Blanchard, Nicolas; Simmonds, Rachel; Inglese, James; Du, Yuchun; Demangel, Caroline; High, Stephen; Paavilainen, Ville O.; Shi, Wei Q. [Journal of the American Chemical Society, 2019, vol. 141, # 21, p. 8450 - 8461]

78
2-[(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6H,6aH,7H,10H,10aH-benzo[c]isochromen-1-yl]oxy}acetic acid [ No CAS ]
[ 359860-27-8 ]
N-[2-(2-{2-[2-(2-[(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6H,6aH,7H,10H,10aH-benzo[c]isochromen-1-yl]oxy}acetamido)ethoxy]ethoxy}ethoxy)ethyl]-5-{2-oxo-hexahydro-1H-thieno[3,4-d]imidazolidin-4-yl}pentanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
16%	Stage #1: 2-[(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6H,6aH,7H,10H,10aH-benzo[c]isochromen-1-yl]oxy}acetic acid With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane; N,N-dimethyl-formamide at 20℃; for 1h; Inert atmosphere; Stage #2: N-(2-(2-(2-(2-amidoethoxy)ethoxy)ethoxy)ethoxy)biotinamide In dichloromethane; N,N-dimethyl-formamide at 20℃; for 46h;

Reference： [1]Kang, Shoukai; Davidsen, Kristian; Gomez-Castillo, Luis; Jiang, Huayi; Fu, Xiaonan; Li, Zengpeng; Liang, Yu; Jahn, Molly; Moussa, Mahmoud; Dimaio, Frank; Gu, Liangcai [Journal of the American Chemical Society, 2019, vol. 141, # 28, p. 10948 - 10952]

79
C₁₈H₂₂ClN₅O [ No CAS ]
[ 359860-27-8 ]
N-(2-(2-(2-(2-(((1r,4r)-4-((5-chloro-4-(5-(cyclopropylmethyl)-1-methyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)cyclohexyl)amino)ethoxy)ethoxy)ethoxy)ethyl)-5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
10%	Stage #1: C₁₈H₂₂ClN₅O; N-(2-(2-(2-(2-amidoethoxy)ethoxy)ethoxy)ethoxy)biotinamide In methanol at 15℃; for 5h; Stage #2: With sodium tris(acetoxy)borohydride; acetic acid In methanol at 15 - 50℃; for 24h; Inert atmosphere;	35 Compound AA11. A mixture of compound 13A (92 mg, 255 µmol, 1 eq.) and compound 14A (160 mg, 382 µmol, 1.5 eq.) in MeOH (2 mL) stirred at 15 °C for 5 h. To the mixture was added CH3COOH (31 mg, 510 µmol, 29 µL, 2 eq.) and NaBH(OAc)3 (162 mg, 765 µmol, 3 eq.) in one portion. The reaction mixture was then stirred at 15-50 °C for 24 h under N2. The reaction mixture was cooled to 25 °C and partitioned between H2O (10 mL) and EtOAc (15 mL). The organic phase was separated and washed with brine (10 mL), dried over Na2SO4, and concentrated in vacuo. The residue was purified by prep-HPLC (HCl condition) to afford compound AA11 (20 mg, 25 µmol, 10% yield). 1H NMR (CD3OD, 400 MHz) δ 8.42-8.21 (m, 2H), 4.60-4.47 (m, 1H), 4.38-4.25 (m, 1H), 3.90 (br s, 1H), 3.81 (s, 3H), 3.64 (br s, 2H), 3.54 (s, 4H), 3.50 (br s, 2H), 3.42 (br t, J = 5.2 Hz, 2H), 3.26 (br t, J = 5.2 Hz, 2H), 3.15 (br s, 6H), 3.08 (br d, J = 6.5 Hz, 2H), 2.85 (br dd, J = 4.3, 13.1 Hz, 1H), 2.64 (br d, J = 13.3 Hz, 1H), 2.15 (br t, J = 6.8 Hz, 4H), 2.09 (br s, 2H), 1.68-1.38 (m, 8H), 1.36-1.21 (m, 2H), 0.94 (br s, 1H), 0.38 (br d, J = 7.2 Hz, 2H), 0.14 (br s, 2H).

Reference： [1]Current Patent Assignee: Yissum Research & Development (in: Hebrew University); HEBREW UNIVERSITY OF JERUSALEM - WO2019/155468, 2019, A1 Location in patent: Paragraph 00519; 00522

80
[ 755039-56-6 ]
[ 359860-27-8 ]
4-(((R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-5,6,7,8-tetrahydropteridin-2-yl)amino)-3-methoxy-N-(13-oxo-17-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)-3,6,9-trioxa-12-azaheptadecyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 24h;

Reference： [1]Remillard, David; Buckley, Dennis L.; Seo, Hyuk-Soo; Ferguson, Fleur M.; Dhe-Paganon, Sirano; Bradner, James E.; Gray, Nathanael S. [ACS Medicinal Chemistry Letters, 2019, vol. 10, # 10, p. 1443 - 1449]

81
[ 526191-19-5 ]
[ 359860-27-8 ]
C₄₂H₆₂N₆O₇S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane

Reference： [1]Current Patent Assignee: SCRIPPS RESEARCH - WO2020/18596, 2020, A1 Location in patent: Paragraph 0257-0258

82
[ 134179-38-7 ]
[ 58-85-5 ]
[ 359860-27-8 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethylamine; biotin With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In methanol; acetonitrile at 20℃; Stage #2: With palladium on activated charcoal; hydrogen; acetic acid

Reference： [1]Current Patent Assignee: SCRIPPS RESEARCH - WO2020/18596, 2020, A1 Location in patent: Paragraph 0262-0263

83
C₂₆H₄₀N₂O₃ [ No CAS ]
[ 359860-27-8 ]
C₄₄H₇₂N₆O₇S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 5h; Inert atmosphere;	Procedure for synthesis of biotinylated ST: General procedure: Derivatives ST-3 or ST-4(50 mg, 0.12 mmol) and biotin-PEG3-amine (68 mg, 0.16 mmol) weredissolved in dry DMF (3 mL) under argon atmosphere. SuccessivelyHOBt (8 mg, 0.06 mmol), 4-DMAP (20 mg, 0.16 mmol) and EDC·HCl(31 mg, 0.016 mmol) were added and the mixture was stirred 5 h at RT.The solvent was removed under reduced pressure and the residue waspurified twice by column chromatography (CHCl3-MeOH, 50/1 → 10/1). The fractions containing product were collected and the solvent wasevaporated. The residue was re-dissolved in CHCl3 and filtered.Biotinylated derivatives were obtained as white foamy solids; ST-9(63 mg, 65%) and ST-10 (62 mg, 64%).Compound ST-9: RF = 0.35 in DCM-MeOH, 10/1. 1H NMR(300 MHz, CDCl3) δ ppm: 0.72 (s, 3H, CH3), 0.84 (s, 3H, CH3), 1.19 (s,3H, CH3), 1.22-1.89 (m, 23H), 1.98-2.29 (m, 6 H), 2.50-2.76 (m, 3 H),2.82-2.92 (m, 1 H), 3.06-3.15 (m, 1 H, biotCH), 3.40 (q, J = 4.7 Hz, 4H), 3.53 (q, J = 4.7 Hz, 4 H), 3.60 (s, 8 H), 4.01 (t, J = 6.8 Hz, 2 H),4.28 (dd, J = 7.8, 4.8 Hz, 1 H, biotCH), 4.47 (dd, J = 7.3, 4.8 Hz, 1 H,biotCH), 5.81 (br. s., 1 H), 6.62 (br. s., 1 H), 6.70 (t, J = 5.1 Hz, 1 H),6.94 (t, J = 5.1 Hz, 1 H), 7.05 (s, 1 H, pyrCH); Fig. S1. 13C NMR(75 MHz, CDCl3) δ ppm: 11.79, 14.16, 21.04, 22.96, 23.55, 25.86,26.03, 27.71, 28.32, 28.44, 29.58, 30.23, 31.75, 31.89, 35.04, 35.92,36.12, 36.56, 36.87, 39.16, 39.31, 39.35, 40.73, 42.81, 45.60, 50.79,51.67, 54.06, 55.89, 60.44, 61.99, 70.16, 70.19, 70.30, 70.55, 70.58,81.88, 115.33, 127.38, 147.66, 164.35, 173.13, 173.66; Fig. S2. αD20αD20 = +30.8 (c = 0.25, CHCl3). ESI-HRMS+: m/z calculated forC44H73N6O7S [M+H]+ 829.52560, found 829.5246 Da; calculated forC44H72N6NaO7S [M + Na]+ 851.50754, found 851.50610 Da; Fig. S7.

Reference： [1]Huml, Lukáš; Havlová, Dominika; Longin, Ondřej; Staňková, Eliška; Holubová, Barbora; Kuchař, Martin; Prokudina, Elena; Rottnerová, Zdeňka; Zimmermann, Tomáš; Drašar, Pavel; Lapčík, Oldřich; Jurášek, Michal [Steroids, 2020, vol. 155]

84
C₂₆H₄₀N₂O₃ [ No CAS ]
[ 359860-27-8 ]
C₄₄H₇₂N₆O₇S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 5h; Inert atmosphere;	Procedure for synthesis of biotinylated ST: General procedure: Derivatives ST-3 or ST-4(50 mg, 0.12 mmol) and biotin-PEG3-amine (68 mg, 0.16 mmol) weredissolved in dry DMF (3 mL) under argon atmosphere. SuccessivelyHOBt (8 mg, 0.06 mmol), 4-DMAP (20 mg, 0.16 mmol) and EDC·HCl(31 mg, 0.016 mmol) were added and the mixture was stirred 5 h at RT.The solvent was removed under reduced pressure and the residue waspurified twice by column chromatography (CHCl3-MeOH, 50/1 → 10/1). The fractions containing product were collected and the solvent wasevaporated. The residue was re-dissolved in CHCl3 and filtered.Biotinylated derivatives were obtained as white foamy solids; ST-9(63 mg, 65%) and ST-10 (62 mg, 64%).

Reference： [1]Huml, Lukáš; Havlová, Dominika; Longin, Ondřej; Staňková, Eliška; Holubová, Barbora; Kuchař, Martin; Prokudina, Elena; Rottnerová, Zdeňka; Zimmermann, Tomáš; Drašar, Pavel; Lapčík, Oldřich; Jurášek, Michal [Steroids, 2020, vol. 155]

85
17α-methyl pyrazolo[3′,4′:3,2]-5α-androstane-17β-yl-hemisuccinate [ No CAS ]
[ 359860-27-8 ]
C₄₃H₆₈N₆O₈S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	With dmap; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 5h; Inert atmosphere;	Procedure for synthesis of biotinylated ST: General procedure: Derivatives ST-3 or ST-4(50 mg, 0.12 mmol) and biotin-PEG3-amine (68 mg, 0.16 mmol) weredissolved in dry DMF (3 mL) under argon atmosphere. SuccessivelyHOBt (8 mg, 0.06 mmol), 4-DMAP (20 mg, 0.16 mmol) and EDC·HCl(31 mg, 0.016 mmol) were added and the mixture was stirred 5 h at RT.The solvent was removed under reduced pressure and the residue waspurified twice by column chromatography (CHCl3-MeOH, 50/1 → 10/1). The fractions containing product were collected and the solvent wasevaporated. The residue was re-dissolved in CHCl3 and filtered.Biotinylated derivatives were obtained as white foamy solids; ST-9(63 mg, 65%) and ST-10 (62 mg, 64%).

Reference： [1]Huml, Lukáš; Havlová, Dominika; Longin, Ondřej; Staňková, Eliška; Holubová, Barbora; Kuchař, Martin; Prokudina, Elena; Rottnerová, Zdeňka; Zimmermann, Tomáš; Drašar, Pavel; Lapčík, Oldřich; Jurášek, Michal [Steroids, 2020, vol. 155]

86
[ 101187-40-0 ]
[ 58-85-5 ]
[ 359860-27-8 ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: 1-Boc-amine-11-amino-3,6,9-trioxaundecane; biotin With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: With trifluoroacetic acid In dichloromethane	7 General Procedure for Synthesis of Compounds HXC79 [0317] DIPEA (5 eq.) and HATU (1.2 eq.) were added to a solution of the sl7 (48.8 mg, (0610) 0.2 mmol) and compound sl4 (1.1 eq.) in DMF (2 mL). After 30 min at room temperature, the mixture was subject to HPLC purification to afford compound si 8 with 87% yield after deprotected by TFA/DCM.

Reference： [1]Current Patent Assignee: UNIVERSITY OF MICHIGAN - WO2020/142228, 2020, A1 Location in patent: Paragraph 0317

87
(S)-3-((tert-butoxycarbonyl)amino)-3-(4-(4-methylthiazol-5-yl)phenyl)propanoic acid [ No CAS ]
[ 359860-27-8 ]
C₃₁H₄₆N₆O₆S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	Stage #1: (S)-3-((tert-butoxycarbonyl)amino)-3-(4-(4-methylthiazol-5-yl)phenyl)propanoic acid; N-(2-(2-(2-(2-amidoethoxy)ethoxy)ethoxy)ethoxy)biotinamide With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: With trifluoroacetic acid In dichloromethane	7 DIPEA (5 eq.) and HATU (1.2 eq.) were added to a solution of the sl8 (41.8 mg, (0612) 0.1 mmol) and compound 63 (1.1 eq.) in DMF (2 mL). After 30 min at room temperature, the mixture was subject to HPLC purification to afford compound si 9 with 82% yield after deprotected by TFA/DCM.

Reference： [1]Current Patent Assignee: UNIVERSITY OF MICHIGAN - WO2020/142228, 2020, A1 Location in patent: Paragraph 0318

88
(S)-3-((tert-butoxycarbonyl)amino)-3-(4-(4-methylthiazol-5-yl)phenyl)propanoic acid [ No CAS ]
[ 359860-27-8 ]
(2S',4R)-4-hydroxy-1-(3-methyl-2-(3-methylisoxazol-5-yl)butanoyl)-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)-3,17-dioxo-21-((3aS,4S',6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)-7,10,13-trioxa-4,16-diazahenicosyl)pyrrolidine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.5 h / 20 °C 2: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.5 h / 20 °C

Reference： [1]Current Patent Assignee: UNIVERSITY OF MICHIGAN - WO2020/142228, 2020, A1

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	359860-27-8	MDL No. :	MFCD09952640
Formula :	C₁₈H₃₄N₄O₅S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	KIJSBKNJFAUJFV-ZOBUZTSGSA-N
M.W :	418.55	Pubchem ID :	50896259
Synonyms :	(+)-Biotinyl 3,6,9-trioxaundecanediamine	Chemical Name :	N-(2-(2-(2-(2-Aminoethoxy)ethoxy)ethoxy)ethyl)-5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanamide

Num. heavy atoms :	28
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.89
Num. rotatable bonds :	17
Num. H-bond acceptors :	6.0
Num. H-bond donors :	4.0
Molar Refractivity :	114.99
TPSA :	149.24 Å²

GI absorption :	Low
BBB permeant :	No
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-9.78 cm/s

Log Po/w (iLOGP) :	3.16
Log Po/w (XLOGP3) :	-1.3
Log Po/w (WLOGP) :	-0.92
Log Po/w (MLOGP) :	-0.75
Log Po/w (SILICOS-IT) :	1.48
Consensus Log Po/w :	0.33

[ CAS No. 359860-27-8 ] {[proInfo.proName]}

Quality Control of [ 359860-27-8 ]

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Product Details of [ 359860-27-8 ]

Calculated chemistry of [ 359860-27-8 ]

Physicochemical Properties

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Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 359860-27-8 ]

Application In Synthesis of [ 359860-27-8 ]

[ 359860-27-8 ] Synthesis Path-Downstream 1~88

Related Functional Groups of
[ 359860-27-8 ]

Ethers

Amides

Amines

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[ 359860-27-8 ]

Other Aliphatic Heterocycles

Precautionary Statements-General

Prevention

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Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Lipinski :	0.0
Ghose :	None
Veber :	2.0
Egan :	1.0
Muegge :	1.0
Bioavailability Score :	0.55

Log S (ESOL) :	-0.49
Solubility :	134.0 mg/ml ; 0.321 mol/l
Class :	Very soluble
Log S (Ali) :	-1.34
Solubility :	19.3 mg/ml ; 0.0461 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-4.3
Solubility :	0.021 mg/ml ; 0.0000502 mol/l
Class :	Moderately soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	4.61

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P301+P312-P302+P352-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H320-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.
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P281	Use personal protective equipment as required.
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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
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P304	IF INHALED:
P305	IF IN EYES:
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P313	Get medical advice/attention.
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P320
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P321
P322
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P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

[ CAS No. 359860-27-8 ] {[proInfo.proName]}

Quality Control of [ 359860-27-8 ]

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Product Details of [ 359860-27-8 ]

Calculated chemistry of [ 359860-27-8 ]

Physicochemical Properties

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Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

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Application In Synthesis of [ 359860-27-8 ]

[ 359860-27-8 ] Synthesis Path-Downstream 1~88

Related Functional Groups of [ 359860-27-8 ]

Ethers

Amides

Amines

Related Parent Nucleus of [ 359860-27-8 ]

Other Aliphatic Heterocycles

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[ 359860-27-8 ]

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[ 359860-27-8 ]