Name: 147-94-4|4-Amino-1-((2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one|98%
Brand: Ambeed
SKU: A568740
Price: 5.0 USD
Availability: InStock
Rating: 94 (22 reviews)

1
[ 10212-25-6 ]
[ 147-94-4 ]

Yield	Reaction Conditions	Operation in experiment
83%	In ethanol; water;	EXAMPLE 2 <strong>[10212-25-6]2,2'-O-<strong>[10212-25-6]cyclocytidine hydrochloride</strong></strong> (6.5 g) was dissolved in 35 mL water at 80 C. The solution was cooled to room temperature and t-butylarnine (2.8 g) was added and the mixture stirred for 2 hours. Thereafter, the solvent was evaporated under vacuum and ethanol (16 g) was added. The mixture was stirred at room temperature for 12 hours. Filtration of the resulting precipitation yielded 5 g of pure cytarabine after drying, which corresponds to a yield of 83%. The product was characterized by comparison of its melting point, and NMR and IR spectra with those previously reported for cytarabine.

Reference： [1]Patent: US5610292,1997,A
[2]Carbohydrate Research,1981,vol. 97,p. 139 - 146

2
[ 6742-07-0 ]
[ 147-94-4 ]

Yield	Reaction Conditions	Operation in experiment
88%	With ammonia at 25℃;
	With ammonia for 16h; Ambient temperature; Yield given;

Reference： [1]Saladino, Raffaele; Mincione, Enrico; Crestini, Claudia; Mezzetti, Maurizio [Tetrahedron, 1996, vol. 52, # 19, p. 6759 - 6780]
[2]Divakar, K.J.; Reese, Colin B. [Journal of the Chemical Society. Perkin transactions I, 1982, p. 1171 - 1176]

3
[ 5211-86-9 ]
[ 147-94-4 ]
N⁴-(piperidinomethylene)arabinocytidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	In N,N-dimethyl-formamide Ambient temperature;
85%	In N,N-dimethyl-formamide at 20℃;	11 Ara-C (500 mg, 2.05 mmol) in DMF (10 mL) was reacted with N-(dimethoxy methyl)piperidine (2.7 g, 16.8 mmol) for several hours at room temperature. The contents were evaporated and the residue chromoatographed over silica gel using 1-6% MeOH in CH2Cl2. The desired fractions were collected and evaporated. The foam obtained was recrystallized from a mixture of ethanol, CH2Cl2, and ethyl acetate to give N4-[Piperidinomethylene]arabinocytidine (594 mg, 85%). This procedure is taken from Kerr et al., J. Pharm. Sci. 83(4): 582-586 (1994).

Reference： [1]Kerr; Kalman [Journal of Pharmaceutical Sciences, 1994, vol. 83, # 4, p. 582 - 586]
[2]Current Patent Assignee: MERCK & CO INC - US2006/198824, 2006, A1 Location in patent: Page/Page column 28

4
[ 4432-76-2 ]
[ 147-94-4 ]
N⁴-<(diethylamino)methylene>arabinocytidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	In N,N-dimethyl-formamide for 8h; Ambient temperature;
90%	In N,N-dimethyl-formamide	7 Ara-C (500 mg, 2.05 mmol) in DMF (2 mL) was reacted with diethylformamide dimethyl acetal (2.16 g, 14.7 mmol). After evaporation, the recrystallization of the residue from a variety of solvents proved difficult. The residue was finally crystallized from a solution of 4% MeOH in CH2Cl2, to give N4-[(Diethylamino)methylene]arabinocytidine as fine colorless, whitish crystals (601 mg, 90%). This procedure is taken from Kerr et al., J. Pharm. Sci. 83(4): 582-586 (1994).

Reference： [1]Kerr; Kalman [Journal of Pharmaceutical Sciences, 1994, vol. 83, # 4, p. 582 - 586]
[2]Current Patent Assignee: MERCK & CO INC - US2006/198824, 2006, A1 Location in patent: Page/Page column 28

5
[ 770-71-8 ]
[ 147-94-4 ]
[ 93604-98-9 ]

Reference： [1]Journal of Medicinal Chemistry,1985,vol. 28,p. 171 - 177

6
[ 6240-11-5 ]
[ 147-94-4 ]
[ 93604-99-0 ]

Reference： [1]Journal of Medicinal Chemistry,1985,vol. 28,p. 171 - 177

7
[ 19449-28-6 ]
[ 147-94-4 ]
N⁴-<(diisopropylamino)methylene>arabinocytidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	In N,N-dimethyl-formamide for 8h; Ambient temperature;
93%	In N,N-dimethyl-formamide	10 Ara-C (500 mg, 2.05 mmol) in DMF (10 mL) was reacted with diisopropylformamide dimethyl acetal (2.3 g, 13.2 mmol). After evaporation, the residue was crystallized from ethanol-ether to give pale lemon-colored crystals of N4-[(Diisopropylamino)methylene]arabinocytidine (723 mg, 93%). This procedure is taken from Kerr et al., J. Pharm. Sci. 83(4): 582-586 (1994).

Reference： [1]Kerr; Kalman [Journal of Pharmaceutical Sciences, 1994, vol. 83, # 4, p. 582 - 586]
[2]Current Patent Assignee: MERCK & CO INC - US2006/198824, 2006, A1 Location in patent: Page/Page column 28

8
[ 5211-95-0 ]
[ 147-94-4 ]
N⁴-<(dipropylamino)methylene>arabinocytidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	In N,N-dimethyl-formamide for 8h; Ambient temperature;
85%	In N,N-dimethyl-formamide	8 Ara-C (85 mg, 0.35 mmol) in DMF (2 mL) was reacted with dipropylformamide dimethyl acetal (0.9 g, 5.14 mmol). Evaporation and crystallization from ethanol-ethyl acetate gave N4-[(Dipropylamino)methylene]arabinocytidine (104 mg, 85%). This procedure is taken from Kerr et al., J. Pharm. Sci. 83(4): 582-586 (1994).

Reference： [1]Kerr; Kalman [Journal of Pharmaceutical Sciences, 1994, vol. 83, # 4, p. 582 - 586]
[2]Current Patent Assignee: MERCK & CO INC - US2006/198824, 2006, A1 Location in patent: Page/Page column 28

9
[ 69304-37-6 ]
[ 147-94-4 ]
[ 75331-99-6 ]

Yield	Reaction Conditions	Operation in experiment
98%	In pyridine for 1h; Ambient temperature;
90%	With pyridine at 20℃; for 4h;
70%	With pyridine at 25℃; for 2h;	470 Preparative Example 470:1 ,3-dichloro-i ,1 ,3,3-tetraisopropyl-disiloxane (1.70 mL, 5.50 mmol) was added to a solution of the starting material (1.22 g, 5.00 mmol) in anhydrous pyridine (20 mL) at 25 °C. The mixture was stirred at 25 °C for 2 h, evaporated and the residue was partitioned between H2O (100 mL) and CH2Cl2 (50 mL). The aqueous part was extracted with CH2Cl2 (2x50 mL) and the combined extracts were dried over MgSO4, filtered, the solvent was evaporated and then PhCH3 (2x100 mL) was added to the residue and it was evaporated . The residue was purified by chromatography on silica gel with 15:1 CHgCl2ZMeOH as eluent. 1.70 g (70 %) of the product was obtained as white solid. MH+ = 486.

In pyridine for 3h; Ambient temperature;

Reference： [1]Markiewicz, Wojciech T.; Padyukova, Nelly Sh.; Samek, Zdenek; Smrt, Jiri [Collection of Czechoslovak Chemical Communications, 1980, vol. 45, # 6, p. 1860 - 1865]
[2]Current Patent Assignee: NUCANA PLC - WO2020/201751, 2020, A1 Location in patent: Paragraph 00116
[3]Current Patent Assignee: MERCK & CO INC - WO2009/61781, 2009, A1 Location in patent: Page/Page column 96-97
[4]Robins, Morris J.; Wilson, John S.; Sawyer, Lindsay; James, Michael N. G. [Canadian Journal of Chemistry, 1983, vol. 61, p. 1911 - 1920]

10
[ 40615-36-9 ]
[ 147-94-4 ]
[ 82845-90-7 ]

Yield	Reaction Conditions	Operation in experiment
95%	With pyridine In N,N-dimethyl-formamide at -5℃; for 1h;

Reference： [1]Ogilvie, Kelvin K.; McGee, Danny P. C.; Boisvert, Suzanne M.; Hakimelahi, Gholam H.; Proba, Zbigniew A. [Canadian Journal of Chemistry, 1983, vol. 61, p. 1204 - 1212]

11
[ 65956-63-0 ]
[ 147-94-4 ]
[ 73532-83-9 ]

Yield	Reaction Conditions	Operation in experiment
79%	With phospholipase D from Streptomyces sp. AA 586 In chloroform; water at 45℃; for 6h; sodium acetate buffer, CaCl₂, pH=5.8;

Reference： [1]Shuto, Satoshi; Imamura, Shigeyuki; Fukukawa, Kiyofumi; Ueda, Tohru [Chemical and pharmaceutical bulletin, 1988, vol. 36, # 12, p. 5020 - 5023]

12
[ 4235-95-4 ]
[ 147-94-4 ]
(Z)-Octadec-9-enoic acid (R)-2-[(2R,3S,4S,5R)-5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethoxy]-hydroxy-phosphoryloxy}-1-((Z)-octadec-9-enoyloxymethyl)-ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With CaCl₂ buffer; sodium acetate; acetic acid In chloroform at 30℃; for 4h; phospholipase D from Streptomyces sp., pH 6.5;

Reference： [1]Wang; Schuster; Wang; Wong [Journal of the American Chemical Society, 1993, vol. 115, # 23, p. 10487 - 10491]

13
[ 35418-55-4 ]
[ 147-94-4 ]
[ 62-49-7 ]
Hexadecanoic acid (S)-2-[(2R,3S,4S,5R)-5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethoxy]-hydroxy-phosphoryloxy}-1-hexadecanoyloxymethyl-ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	In hydrogenchloride; chloroform at 45℃; for 6h; pH 4.5;

Reference： [1]Shuto, Satoshi; Ueda, Shigeru; Imamura, Shigeyuki; Fukukawa, Kiyofumi; Matsuda, Akira; Ueda, Tohru [Tetrahedron Letters, 1987, vol. 28, # 2, p. 199 - 202]

14
[ 84366-67-6 ]
[ 147-94-4 ]
[ 62-49-7 ]
(Z)-Octadec-9-enoic acid (S)-2-[(2R,3S,4S,5R)-5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethoxy]-hydroxy-phosphoryloxy}-1-((Z)-octadec-9-enoyloxymethyl)-ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	In hydrogenchloride; chloroform at 45℃; for 6h; pH 4.5;

Reference： [1]Shuto, Satoshi; Ueda, Shigeru; Imamura, Shigeyuki; Fukukawa, Kiyofumi; Matsuda, Akira; Ueda, Tohru [Tetrahedron Letters, 1987, vol. 28, # 2, p. 199 - 202]

15
[ 5564-73-8 ]
[ 147-94-4 ]
N⁴-(pyrrolidinomethylene)arabinocytidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	In N,N-dimethyl-formamide for 8h; Ambient temperature;
89%	In N,N-dimethyl-formamide	13 Ara-C (100 mg, 0.41 mmol) in DMF (5 mL) was reacted with N-(dimethoxymethyl)pyrrolidine (0.9 g, 6.2 mmol). Evaporation and subsequent crystallization from ethyl acetate-ether gave N4-[Pyrrolidinomethylene]arabinocytidine (119 mg, 89%). This procedure is taken from Kerr et al., J. Pharm. Sci. 83(4): 582-586 (1994).

Reference： [1]Kerr; Kalman [Journal of Pharmaceutical Sciences, 1994, vol. 83, # 4, p. 582 - 586]
[2]Current Patent Assignee: MERCK & CO INC - US2006/198824, 2006, A1 Location in patent: Page/Page column 29

16
[ 18162-48-6 ]
[ 147-94-4 ]
[ 82845-96-3 ]

Yield	Reaction Conditions	Operation in experiment
95%	With 3-picoline-N-oxide; silver nitrate In tetrahydrofuran for 2h; Ambient temperature;
92%	With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 14h;
	With 1H-imidazole In N,N-dimethyl-formamide; toluene at -5 - 5℃;	1.1 Synthesis of compound 2 Commercial cytarabine (400g, 1.65mol, 1.0equiv) and imidazole (4.1mol) were added to anhydrous DMF (3.6L, 9vol), the reaction system was reduced to -5 to 5 ° C, and then 50% wt tert A toluene solution of butyldimethylchlorosilane (3.54 mol) was reacted at 5 to 15 ° C for 15 to 20 hours. 15% sodium chloride solution (8vol) was added to quench the reaction, and then ethyl acetate (12vol) was added for extraction. The organic phase was collected for the next reaction. Proton spectrum (400MHz, DMSO-d6) is shown in Figure 1.

Reference： [1]Ogilvie; Hakimelahi; Proba; McGee [Tetrahedron Letters, 1982, vol. 23, # 19, p. 1997 - 2000]
[2]Location in patent: experimental part Chhikara, Bhupender S.; Mandal, Deendayal; Parang, Keykavous [European Journal of Medicinal Chemistry, 2010, vol. 45, # 10, p. 4601 - 4608]
[3]Current Patent Assignee: NANJING UNIVERSITY - CN110590862, 2019, A Location in patent: Paragraph 0026-0030

17
[ 4637-24-5 ]
[ 147-94-4 ]
[ 60342-57-6 ]

Yield	Reaction Conditions	Operation in experiment
100%	In N,N-dimethyl-formamide for 8h; Ambient temperature;
100%	In N,N-dimethyl-formamide	6 Ara-C (300 mg, 1.23 mmol) in DMF (5 mL) was reacted with dimethylformamide dimethyl acetal (1.7 g, 14.2 mmol). On evaporation and crystallization from a minimum amount of ethanol, white crystals of N4-[(Dimethylamino)methylene]arabinocytidine were obtained (371 mg, 100%). This procedure is taken from Kerr et al., J. Pharm. Sci. 83(4): 582-586 (1994).

Reference： [1]Kerr; Kalman [Journal of Pharmaceutical Sciences, 1994, vol. 83, # 4, p. 582 - 586]
[2]Current Patent Assignee: MERCK & CO INC - US2006/198824, 2006, A1 Location in patent: Page/Page column 28

18
[ 75-36-5 ]
[ 147-94-4 ]
[ 58227-71-7 ]

Yield	Reaction Conditions	Operation in experiment
96%	With acetic acid In chloroform

Reference： [1]Breiner; Rose; Dunn; MacDiarmid; Bardos [Journal of Medicinal Chemistry, 1990, vol. 33, # 9, p. 2596 - 2602]

19
[ 100-49-2 ]
[ 147-94-4 ]
[ 93604-97-8 ]

Reference： [1]Journal of Medicinal Chemistry,1985,vol. 28,p. 171 - 177

20
[ 19449-31-1 ]
[ 147-94-4 ]
N⁴-(morpholinomethylene)arabinocytidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	In N,N-dimethyl-formamide for 8h; Ambient temperature;
93%	In N,N-dimethyl-formamide	12 Ara-C (100 mg, 0.41 mmol) in DMF (5 mL) was reacted with N-(dimethoxymethyl)morpholine (1.35 g, 9.3 mmol). Evaporation and subsequent crystallization from ethyl acetate-ether gave N4-[Morpholinomethylene]arabinocytidine (130 mg, 93%). This procedure is taken from Kerr et al., J. Pharm. Sci. 83(4): 582-586 (1994).

Reference： [1]Kerr; Kalman [Journal of Pharmaceutical Sciences, 1994, vol. 83, # 4, p. 582 - 586]
[2]Current Patent Assignee: MERCK & CO INC - US2006/198824, 2006, A1 Location in patent: Page/Page column 28

21
[ 147-94-4 ]
[ 3083-77-0 ]

Yield	Reaction Conditions	Operation in experiment
> 99%	With cytidine deaminase enzyme; In aq. phosphate buffer; at 37℃; for 0.0833333h;pH 7;Enzymatic reaction;	Comparative Example 6: Deamination of cytarabine (cytosine arabinoside) to uridine arabinoside A 100 mM solution of cytarabine (495 muIota_) in 100 mM phosphate buffer at pH 7 was mixed with 50 muIota_ of cytidine deaminase enzyme solution containing >300 AU in phosphate buffer. The reaction was performed at 37C during 5 minutes and stopped with HCI. Then, the crude reaction was filtered through a 10 KDa membrane, and a portion was diluted and analyzed by HPLC-UV-DAD. The expected uridine arabinoside was identified by comparison to a standard sample, and formed in quantitative yield (>99%).

Reference： [1]Patent: WO2016/146808,2016,A1 .Location in patent: Page/Page column 30
[2]Carbohydrate Research,1981,vol. 97,p. 139 - 146
[3]Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry,1986,vol. 40,p. 798 - 805
[4]Pharmazie,1995,vol. 50,p. 382 - 387
[5]Pharmaceutical Chemistry Journal,2000,vol. 34,p. 451 - 454
[6]Journal of Agricultural and Food Chemistry,2014,vol. 62,p. 1796 - 1801

22
[ 147-94-4 ]
[ 116981-58-9 ]

Yield	Reaction Conditions	Operation in experiment
65%	With potassium hydroxide; hydrogen at 20℃; for 5h;

Reference： [1]Yakovleva, L. A.; Akulov, G. P.; Nagorskii, A. I.; Patokina, N. A.; Kaminskii, Yu. L.; Zhuk, R. Z. [Chemistry of Heterocyclic Compounds, 1988, vol. 24, p. 79 - 83][Khimiya Geterotsiklicheskikh Soedinenii, 1988, vol. 24, # 1, p. 95 - 99]

23
[ 147-94-4 ]
[ 7075-11-8 ]

Reference： [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 4569 - 4575

24
[ 18162-48-6 ]
[ 147-94-4 ]
[ 90362-54-2 ]

Yield	Reaction Conditions	Operation in experiment
98%	With pyridine; silver nitrate; triethylamine In tetrahydrofuran at 20℃; for 26h;
90%	With 1H-imidazole; dmap In N,N-dimethyl-formamide at 63℃; Cooling with ice; Inert atmosphere;	1.1 Step 1) Synthesis of compound PA4101-2 dissolving a compound PA4101-1 (Cytarbine, 9.5 g, 39 mmol) and imidazole (18 g, 264 mmol) in DMF (100 mL), adding 4-dimethylaminopyridine ((DMAP, 3.8 g, 31 mmol), adding tert-butyldimethylsilyl chloride (TBSCI, 30 g, 198 mmol) slowly in an ice bath, under nitrogen protection, carrying out reaction at 63 °C while stirring overnight, after completing the reaction, adding a reaction solution slowly to water (400 mL), followed by extraction with ethyl acetate (3 × 300 mL), washing by saturated brine, drying over anhydrous sodium sulfate, followed by filtration, spin-drying, and separation and purification by silica gel chromatographic column to obtain PA4101-2 (20.6 g), with yield of 90%.
85%	With 1H-imidazole In N,N-dimethyl-formamide at 20℃;

84%	With 1H-imidazole; dmap In N,N-dimethyl-formamide at 22℃; for 48h;
72%	With 1H-imidazole; dmap In N,N-dimethyl-formamide at 20 - 60℃;
69%	With 1H-imidazole In N,N-dimethyl-formamide
	With pyridine; 1H-imidazole at 20℃;

Reference： [1]Jung, Kang-Yeoun; Hohl, Raymond J.; Wiemer, Andrew J.; Wiemer, David F. [Bioorganic and Medicinal Chemistry, 2000, vol. 8, # 10, p. 2501 - 2509]
[2]Current Patent Assignee: ZHEJIANG PALO ALTO PHARMACEUTICALS; ZHEJIANG KANGDE PHARMACEUTICAL - EP3730504, 2020, A1 Location in patent: Paragraph 0070; 0071
[3]Erion, Mark D.; Reddy, K. Raja; Boyer, Serge H.; Matelich, Michael C.; Gomez-Galeno, Jorge; Lemus, Robert H.; Ugarkar, Bheemarao G.; Colby, Timothy J.; Schanzer, Juergen; Van Poelje, Paul D. [Journal of the American Chemical Society, 2004, vol. 126, # 16, p. 5154 - 5163]
[4]Wipf, Peter; Li, Wenjie; Adeyeye, Christianah M.; Rusnak, James M.; Lazo, John S. [Bioorganic and Medicinal Chemistry, 1996, vol. 4, # 10, p. 1585 - 1596]
[5]Bazzanini; Gouy; Peyrottes; Gosselin; Perigaud; Manfredini [Nucleosides, nucleotides and nucleic acids, 2005, vol. 24, # 10-12, p. 1635 - 1649]
[6]Cheon, Eun-Pa; Hong, Joon Hee; Han, Hyo-Kyung [Journal of Pharmacy and Pharmacology, 2006, vol. 58, # 7, p. 927 - 932]
[7]Chen, Xuemei; Wiemer, Andrew J.; Hohl, Raymond J.; Wiemer, David F. [Journal of Organic Chemistry, 2002, vol. 67, # 26, p. 9331 - 9339]

25
[ 219797-98-5 ]
[ 147-94-4 ]
[ 186594-89-8 ]

Yield	Reaction Conditions	Operation in experiment
95%	With TEA In pyridine at 80℃; for 12h;

Reference： [1]Contino, Christiane; Ollier, Monique; Maurizis, Jean Claude; Lacombe, Jean Michel; Pucci, Bernard [Tetrahedron Letters, 1996, vol. 37, # 50, p. 9049 - 9052]

26
[ 219797-99-6 ]
[ 147-94-4 ]
[ 186594-93-4 ]

Yield	Reaction Conditions	Operation in experiment
78%	With TEA In pyridine at 80℃; for 12h;

Reference： [1]Contino, Christiane; Ollier, Monique; Maurizis, Jean Claude; Lacombe, Jean Michel; Pucci, Bernard [Tetrahedron Letters, 1996, vol. 37, # 50, p. 9049 - 9052]

27
[ 196706-06-6 ]
[ 147-94-4 ]

Yield	Reaction Conditions	Operation in experiment
21%	With hydrogen In methanol for 30h; Ambient temperature;

Reference： [1]Kotra, Lakshmi P.; Wang, Pingping; Bartlett, Michael G.; Shanmuganathan, Kirupa; Xu, Zusheng; Cavalcanti, Socrates; Gary Newton; Chu, Chung K. [Journal of Organic Chemistry, 1997, vol. 62, # 21, p. 7267 - 7271]

28
[ 880633-93-2 ]
[ 147-94-4 ]
N4-(5-nitro-1-methylimidazol-2-yl)methoxycarbonyl-1-β-D-arabinofuranosylcytosine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
12%	With sodium hydrogencarbonate In 2,4-dichlorophenoxyacetic acid dimethylamine for 168h;	7 Cytarabine (243 mg, 1.0 mmol), 2-Chlorocarbonyloxymethyl-l-methyl-5- nitroimidazole (439 mg, 2.0 mmol), sodium bicarbonate (336 mg, 4.0 mmol) and DMA (10 mL) were stirred for 7 days. The suspension was filtered and the filtrate concentrated in vacuo. The resultant oil was triturated with DCM; the suspension was filtered, and the solid was washed with DCM then dried at the pump. The solid was dissolved in methanol and then adsorbed on to flash silica. Column chromatography, eluting with 33% then 50% methanol / DCM, furnished an off-white wax (53 mg, 12%); TLC Rf=0.3, 10% methanol / ethyl acetate. NMR (500Mhz, DMSO-d6, δ)7.98 (IH, s, HarH), 7.35 (IH, bs, HarH), 5.99 (IH, s, NCHO), 5.86 (IH, bs, HarH), 5.65 (IH, bs, OH), 5.47 (IH, bs, OH), 5.26 (2H, m, HarCH2O), 5.05 (IH, s, OH), 4.08 (IH, bs, CHOH), 3.95 (3H, s, NCH3), 3.90 (IH, bs, OCHCH2OH), 3.73 (IH, bs, CHOH), 3.62 (2H, m, CH2OH) ppm.The 2-chlorocarbonyloxymethyl-l-methyl-5-nitroimidazole used in the above synthesis was prepared as follows: 2-Hydroxymethyl-l-methyl-5-nitroimidazole (314 mg, 2.0 mmol) in THF (10 mL) was added to phosgene (4 mL, 8.0 mmol) and THF EPO (15 mL) at O0C. The reaction was stirred for 16 h then the solvent was removed in vacuo. The crude chloroformate was used without further purification.2-Hydroxymethyl-l-methyl-5-nitroiniidazole was prepared as follows: Methanolic ammonia (3.6 mL, 25 mmol) was added to a suspension of ronidazole (5 g, 25 mmol) and methanol (25 mL). Potassium carbonate (1.75 g, 12.5 mmol) was added and the reaction mixture heated to 5O0C for 18 h. The solution was cooled to ambient temperature then partitioned (ethyl acetate and brine), the aqueous phase was extracted (ethyl acetate); the organic phases were combined, washed (water then brine) then dried in vacuo. The desired product was obtained as an orange solid (2.3 g, 59%) and was used without further purification.

Reference： [1]Current Patent Assignee: GRAY LABORATORY CANCER RESEARCH TRUST; ANGIOGENE PHARMACEUTICALS LIMITED - WO2006/32921, 2006, A1 Location in patent: Page/Page column 35-36

29
[ 147-94-4 ]
[ 872354-90-0 ]
trans-5'-O-[4-(3-chlorophenyl)-2-oxo-1,3,2-dioxaphosphorinan-2-yl]cytosine-1-β-D-arabinofuranoside [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: arabinosyl cytosine; [4-(3-chloro-phenyl)-[1,3,2]dioxaphosphinan-2-yl]-diisopropyl-amine With 5-methylsulfanyl-1H-tetrazole In N,N-dimethyl-formamide at 20℃; Stage #2: With tert.-butylhydroperoxide In n-heptane; N,N-dimethyl-formamide at -40 - 20℃;

Reference： [1]Erion, Mark D.; Reddy, K. Raja; Boyer, Serge H.; Matelich, Michael C.; Gomez-Galeno, Jorge; Lemus, Robert H.; Ugarkar, Bheemarao G.; Colby, Timothy J.; Schanzer, Juergen; Van Poelje, Paul D. [Journal of the American Chemical Society, 2004, vol. 126, # 16, p. 5154 - 5163]

30
[ 147-94-4 ]
O\-methyl-poly(ethylene glycol)-O-carbonyl-norleucyl-OSu, PEG part M_w 5000 Da; Su: N-succinimido [ No CAS ]
O-methyl-poly(ethylene glycol)-O-carbonyl-norleucyl-(1-β-D-arabinofuranosylcytosin-N⁴-yl), PEG part M_w 5000 Da [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With pyridine at 20℃; for 72h;

Reference： [1]Schiavon; Pasut; Moro; Orsolini; Guiotto; Veronese [European Journal of Medicinal Chemistry, 2004, vol. 39, # 2, p. 123 - 133]

31
[ 147-94-4 ]
O\-methyl-poly(ethylene glycol)-lysyl-OSu, PEG part M_w 10000 Da; Su: N-succinimido [ No CAS ]
O-methyl-poly(ethylene glycol)-lysyl-(1-β-D-arabinofuranosylcytosin-N⁴-yl), PEG part M_w 10000 Da [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With pyridine at 20℃; for 72h;

Reference： [1]Schiavon; Pasut; Moro; Orsolini; Guiotto; Veronese [European Journal of Medicinal Chemistry, 2004, vol. 39, # 2, p. 123 - 133]

32
[ 147-94-4 ]
poly(ethylene glycol)-O,O\-bis-(C(O)NHCH(C(O)-OSu)-(CH₂)3-C(O)-OSu), M_w 10000 Da, Su: N-succinimido, PEG part M_w 10000 Da [ No CAS ]
poly(ethylene glycol)-O,O-bis-(C(O)NHCH(C(O)-Ara-C)-(CH2)3-C(O)-Ara-C), PEG part M_w 10000 Da, Ara-C: 1-β-D-arabinofuranosylcytosin-N⁴-yl [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With pyridine at 20℃; for 72h;

Reference： [1]Schiavon; Pasut; Moro; Orsolini; Guiotto; Veronese [European Journal of Medicinal Chemistry, 2004, vol. 39, # 2, p. 123 - 133]

33
[ 147-94-4 ]
poly(ethylene glycol)-O,O\-bis-(C(O)NHCH(C(O)-NHCH(C(O)-OSu)-(CH₂)3-C(O)-OSu)-(CH₂)3-C(O)-NHCH(C(O)-OSu)-(CH₂)3-C(O)-OSu), Su: N-succinimido, PEG part M_w 10000 Da [ No CAS ]
poly(ethylene glycol)-O,O-bis-(C(O)NHCH(C(O)NHCH(C(O)-Ara-C)-(CH2)3-C(O)-Ara-C)-(CH2)3-C(O)NHCH(C(O)-Ara-C)-(CH2)3-C(O)-Ara-C), PEG part M_w 10000 Da, Ara-C: 1-β-D-arabinofuranosylcytosin-N⁴-yl [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With pyridine at 20℃; for 72h;

Reference： [1]Schiavon; Pasut; Moro; Orsolini; Guiotto; Veronese [European Journal of Medicinal Chemistry, 2004, vol. 39, # 2, p. 123 - 133]

34
[ 10355-50-7 ]
[ 147-94-4 ]
5'-O-vinylsebacoyl-cytarabine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With lipase acrylic resin from Candida antarctica In acetone at 50℃; for 96h;
	With lipase acrylic resin from Candida antarctica In acetone at 50℃; Enzymatic reaction; regioselective reaction;	2.2 Synthesis of the comonomers General procedure: 5-O-vinylsebacoyl-cytarabine (VSC) and 3-O-vinyladipoyl-fluorodeoxyuridine (VAF) were prepared by controllable regio-selective enzymatic transesterifications. The reactions were initiated by adding CAL-B to anhydrous acetone containing cytarabine and divinyl sebacate, or adding PSL-C to THF containing fluorodeoxyuridine and divinyl adipate. The solutions were then incubated at 50 °C and stirred at 250 rpm. The process of the reactions was monitored by TLC. The reactions were terminated by filtering the enzyme and the product was purified by silica gel chromatography. 6-O-vinylsebacoyl-glucose (VSG) was synthesized in the same way while using subtilisin as the catalyst and pyridine as the solvent.

Reference： [1]Wang, Na; Zhi, Chun Chen; De, Shui Lu; Xian, Fu Lin [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 18, p. 4064 - 4067]
[2]Wang, Jianfeng; Yin, Cui; Tang, Guping; Lin, Xianfu; Wu, Qi [International Journal of Pharmaceutics, 2013, vol. 441, # 1-2, p. 291 - 298]

35
[ 10355-49-4 ]
[ 147-94-4 ]
Nonanedioic acid (2R,3S,4S,5R)-5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl ester vinyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With lipase acrylic resin from Candida antarctica In acetone at 50℃; for 96h;

Reference： [1]Wang, Na; Zhi, Chun Chen; De, Shui Lu; Xian, Fu Lin [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 18, p. 4064 - 4067]

36
[ 18162-48-6 ]
[ 147-94-4 ]
[ 82976-97-4 ]

Yield	Reaction Conditions	Operation in experiment
95%	With pyridine; 1H-imidazole at 20℃; for 3h;
85.4%	With pyridine Cooling with ice; Inert atmosphere;	42.1 To an ice-cold solution of arabinocytidine (20.0 g, 82.2 mmol) in anhydrous pyridine (200 mL) was added TBSCl (14.9 g, 98.7 mmol) in small portions under N2. The reaction mixture was stirred at RT overnight. The solvent was removed under vacuum and the residue was diluted with EA (300 mL), washed with water and brine. The organic layer was separated, dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuum to give 5'-O-(?-butydimethylsilyl)arabinocytidine (25.1 g, 85.4%) as a white solid which was used without further purification.
	With pyridine; 1H-imidazole In 1,4-dioxane

Reference： [1]Bazzanini; Gouy; Peyrottes; Gosselin; Perigaud; Manfredini [Nucleosides, nucleotides and nucleic acids, 2005, vol. 24, # 10-12, p. 1635 - 1649]
[2]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2010/108140, 2010, A1 Location in patent: Page/Page column 110
[3]Sk, Ugir Hossain; Kambhampati, Siva P.; Mishra, Manoj K.; Lesniak, Wojciech G.; Zhang, Fan; Kannan, Rangaramanujam M. [Biomacromolecules, 2013, vol. 14, # 3, p. 801 - 810]

37
[ 139285-65-7 ]
[ 147-94-4 ]
[ 157837-83-7 ]

Yield	Reaction Conditions	Operation in experiment
	With 2,4,6-triisopropylphenylsulfonyl chloride In pyridine at 40℃; for 24h;	5.a A solution of 1-O-octadecyl-2-O-benzyl-sn-glycero-3-phosphatidic acid (1) and ara-C in pyridine was treated with TIPS at a temperature of 40°C, over a period of 24h. The reaction was stopped by addition of water and the solvent evaporated under reduced pressure. The crude product purified by chromatography to afford the title compound.

Reference： [1]Current Patent Assignee: HOSTETLER - EP837630, 2007, B1 Location in patent: Page/Page column 12

38
[ 147-94-4 ]
[ 87418-91-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 72 percent / imidazole; DMAP / dimethylformamide / 20 - 60 °C 2: 64 percent / acetic acid / H₂O / 10 h / 50 - 60 °C
	Multi-step reaction with 2 steps 1: 85 percent / imidazole / dimethylformamide / 20 °C 2: 65 percent / aq. trifluoroacetic acid / tetrahydrofuran / 18 h / -10 °C
	Multi-step reaction with 2 steps 1: imidazole; pyridine / 20 °C 2: TFA*H₂O / tetrahydrofuran / 0 °C

Multi-step reaction with 2 steps 1: 1H-imidazole; dmap / N,N-dimethyl-formamide / 63 °C / Cooling with ice; Inert atmosphere 2: hydrogenchloride / ethanol / 4.5 h / 20 °C

Reference： [1]Bazzanini; Gouy; Peyrottes; Gosselin; Perigaud; Manfredini [Nucleosides, nucleotides and nucleic acids, 2005, vol. 24, # 10-12, p. 1635 - 1649]
[2]Erion, Mark D.; Reddy, K. Raja; Boyer, Serge H.; Matelich, Michael C.; Gomez-Galeno, Jorge; Lemus, Robert H.; Ugarkar, Bheemarao G.; Colby, Timothy J.; Schanzer, Juergen; Van Poelje, Paul D. [Journal of the American Chemical Society, 2004, vol. 126, # 16, p. 5154 - 5163]
[3]Chen, Xuemei; Wiemer, Andrew J.; Hohl, Raymond J.; Wiemer, David F. [Journal of Organic Chemistry, 2002, vol. 67, # 26, p. 9331 - 9339]
[4]Current Patent Assignee: ZHEJIANG PALO ALTO PHARMACEUTICALS; ZHEJIANG KANGDE PHARMACEUTICAL - EP3730504, 2020, A1

39
C₁₅H₁₅N₂O₇Pol [ No CAS ]
[ 147-94-4 ]
C₂₀H₂₃N₄O₁₀Pol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap In DMF (N,N-dimethyl-formamide); dichloromethane at 20℃; for 12h;	22 EXAMPLE 22; Compound 22 A solution of 6 (2.0 g, 0.378 mmol), AraC (0.191 g, 0.756 mmol), and DMAP (0.093 g, 0.756 mmol) in anhydrous DMF/DCM (20 mL/20 ML) is stirred at room temperature for 12 hrs. The solvents are partially removed under reduced pressure and the final product is precipitated with ethyl ether (80 mL). The solid is filtered and recrystallized from DMF/METHANOL (35 mL/25 mL) to give 22, shown below. The structure of 22 is confirmed by 13C NMR

Reference： [1]Current Patent Assignee: ENZON PHARMACEUTICALS INC - WO2004/43884, 2004, A2 Location in patent: Page 30

40
[ 147-94-4 ]
[ 69-74-9 ]

Yield	Reaction Conditions	Operation in experiment
96%	With hydrogenchloride; In methanol; at 2 - 25℃; for 4h;	An oven- dried 250 mL round bottom flask equipped with a magnetic stir bar was charged with 3.35 g of cytarabine-HCl and 6.0 mL of DMPU. Into this flask the reaction mixture from example 12 was filtered directly and the DABCO-HCl salt was washed quickly with acetonitrile (1×15 mL). Volatiles were removed on a rotary-evaporator under aspirator vacuum (bath temp <35 C.). The residual oil was briefly kept under high vacuum and stirred at room temperature for 48 h. The reaction mixture was treated with 100 mL of MeOH and stirred for 2 hours at room temperature. The pH of the reaction mixture was adjusted to 7.0 using 25 wt % NaOMe solution in methanol (approximately 13 mL were required). At this stage the reaction mixture was turbid. HPLC was run to insure integrity of the reaction profile. The reaction mixture was evaporated to dryness and the residue was stirred with 50 mL of dichloromethane for 30 minutes at room temperature. The precipitate was collected by filtration, washed with methylene chloride (1×20 mL) and transferred back to the flask, stirred again with 50 mL of dichloromethane for 15 minutes and filtered. The solid was stirred with 200 mL of ethanol for 1-2 hours, filtered and washed with ethanol (2×10 mL). The filtrate was evaporated to dryness to give 4.90 g of a white solid. This solid was dissolved in 10 mL of H2O and stirred at room temperature overnight to give a solid which was collected by filtration, washed with water (2×3 mL) and dried in a vacuum oven to give compound 9, 1.38 g, (26%).
	With hydrogenchloride; In diethyl ether;	A suspension of cytarabin hydrochloric salt (prepared from cytarabin and 1M HC1 in diethyl ether) (839 mg, 3.0 mmol) in DMA (10 ml) was added to the acid chloride of monomethyl azelaic acid (761 mg, 3.45 mmol) in DMA (2 ml) and the mixture stirred at room temperature overnight. NEt3 was added to the reaction mixture (303 mg, 3.0 mmol) and the mixture evaporated in vacuo. The residue was transferred to a flash column with silica gel and separated with (CH2C12/MEOH 10 : 1) as eluent system to leave the product as a white solid. Yield: 278 mg, (21.6 %). 1H-NMR (DMSO-D6, 300 MHz): 5 7.47 (d, 1 H), 7.10 (br d, 2 H), 6.09 (d, 1 H), 5.67 (d, 1 H), 5.60-5. 56 (m, 2 H), 4.33-3. 88 (m, 2 H), 3.98-3. 96 (m, 1 H), 3.94-3. 88 (m, 2 H), 3.57 (s, 3 H), 3.33 (br s, 1 H), 2.34-2. 25 (m, 4 H), 1.54-1. 47 (m, 4 H), 1.22 (br s, 6 H). 3C-NMR (DMSO-D6, 75 MHz) : 8 173.3, 172.8, 165.5, 155.0, 142.8, 92.5, 86.1, 81.7, 76.7, 74.2, 63.6, 51.1, 45.2, 33.5, 33.1, 28.2, 28.1, 24.3, 8.4.

Reference： [1]Patent: US2004/92476,2004,A1 .Location in patent: Page/Page column 22
[2]Patent: WO2005/25552,2005,A2 .Location in patent: Page/Page column 20-21

41
[ 848046-55-9 ]
[ 147-94-4 ]
[ 848046-59-3 ]

Yield	Reaction Conditions	Operation in experiment
36%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In pyridine at 20 - 40℃;	17.7 A Mixture of 7a (0. 50 g, 1.3 mmol), ara-C (1.26 g, 5.2 mmol), HOBT (0.70 g, 5.2 mmol) and EDC-HCl (1.99 g, 10.4 mmol) in anhydrous pyridine (30 ml) was stirred at room temperature for 2h followed by stirring at 40 °C overnight. The solvent was removed in vacuo and the residue was dissolved in CH2CL2 (50 ml) followed by extraction with water (3 x 30 ml) and 0.1 M HCl (2 x 30 ml). The organic phase was dried over anhydrous MGS04 and evaporated in vacuo. The residue was purified by flash chromatography (5-10 % MEOH in CH2C12) to give white crystalline material. Yield: 0.29 g (36 %). H NMR (CDC13) 5 9.70 (d, broad, 1H), 8.08 (s, 1H), 7.28 (q, 1H), 6.79 (s, 1H), 6.59 (s, 1H), 6.10 (s, LH), 5.83 (S, 1H), 5.55-5. 39 (m, 2H), 4.71 (S, 1H), 4.47 (s, 1H), 4.25 (s, 1H), 4.07 (d, 3H), 3.81 (s, broad, 2H), 3. 01- 2.77 (m, 2H), 2.49 (s, 3H), 2.18 (s, 3H), 1.56-1. 43 (m, 6+9H).
36%	With ethylene dichloride hydrochloride; benzotriazol-1-ol In pyridine at 20 - 40℃;	17.7 A Mixture of 7a (0.50 g, 1.3 mmol) , ara-C (1.26 g, 5.2 mmol), HOBT (0.70 g, 5.2 mmol) and EDC-HCl (1.99 g, 10.4 mmol) in anhydrous pyridine (30 ml) was stirred at room temperature for 2h followed by stirring at 40 0C overnight. The solvent was removed in vacuo and the residue was dissolved in CH2Cl2 (50 ml) followed by extraction with water (3 x 30 ml) and 0.1 M HCl (2 x 30 ml) . The organic phase was dried over anhydrous MgSO4 and evaporated in vacuo. The residue was purified by flash chromatography (5-10 % MeOH in CH2Cl2) to give white crystalline material. Yield: 0.29 g (36 %) .1H NMR (CDCl3) δ 9.70 (d, broad, IH), 8.08 (s, IH), 7.28 (q, IH), 6.79 (s, IH), 6.59 (s, IH), 6.10 (s,lH), 5.83 (s, IH), 5.55-5.39 (m, 2H), 4.71 (s, IH), 4.47 (s, IH), 4.25 (s, IH), 4.07 (d, 3H), 3.81 (s, broad, 2H), 3.01- 2.77 (m, 2H), 2.49 (s, 3H), 2.18 (s, 3H), 1.56-1.43 (m, 6+9H) .

Reference： [1]Current Patent Assignee: DRUG DISCOVERY LABORATORY - WO2005/25552, 2005, A2 Location in patent: Page/Page column 22; 26-27
[2]Current Patent Assignee: DRUG DISCOVERY LABORATORY - WO2006/30217, 2006, A2 Location in patent: Page/Page column 31; 36

42
3-(2'-boc-phenylalaninyl-4',6'-dimethylphenyl)-3,3-dimethylpropionic acid [ No CAS ]
[ 147-94-4 ]
C₃₆H₄₆N₄O₁₀ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In pyridine at 20 - 40℃;	17.8 A mixture of 7b (0.67 g, 1.4 mmol), ara-C (1.36 g, 5.6 MMOL), HOBT (0.76 g, 5.6 mmol) and EDC-HC1 (2.15 g, 11.2 mmol) in anhydrous pyridine (35 ml) was stirred at room temperature for 2h followed by stirring at 40 °C overnight. The solvent was removed in vacuo and the residue was dissolved in CH2Cl2 (50 ml) followed by extraction with water (3 x 30 ml) and 0.1 M HC1 (2 x 30 ml). The organic phase was dried over anhydrous MGS04 and evaporated in vacuo. The residue was purified by flash chromatography (5-10 % MEOH in CH2Cl2) to give white crystalline material. Yield: 0.35 g. H NMR (CDC13) 5 9.35-9. 01 (m, 1H), 8.59 (m, 1H), 8.15 (m, 1H), 7.69 (m, 1H), 7.28 (m, 6H), 6.75 (d, 1H), 6.23 (t, 1H), 6.16 (t, LH), 5.90-5. 74 (m, 1H), 5.25 (s, 1H), 4.84 (m, 1H), 4.59 (s, 1H), 4.33 (s, 1H), 4.15 (s, 1H), 3.92-3. 67 (m, 2H), 3.35-3. 25 (m, 1H), 3.20-3. 12 (m, 1H), 2.88 (s, 2H), 2.54-2. 41 (m, 3H), 2.23 (d, 3H), 1.58-1. 44 (m, 6H), 1.38 (s, 9H); 3C NMR 5 173.59, 172.30, 162.45, 156.40, 156.03, 150.23, 149.99, 147.04, 138.60, 137.13, 136. 65, 136. 42,133. 71, 133. 31, 129.92, 129.70, 129.01, 127.52, 124.28, 123.02, 96.95, 89.22, 86.50, 80.63, 74.77, 62. 36, 55.53, 50.71, 40. 02, 38. 33, 32. 57, 31. 93, 28. 71, 25. 82, 20.56.

Reference： [1]Current Patent Assignee: DRUG DISCOVERY LABORATORY - WO2005/25552, 2005, A2 Location in patent: Page/Page column 22; 27

43
[ 23361-28-6 ]
[ 147-94-4 ]
[ 791111-70-1 ]

Yield	Reaction Conditions	Operation in experiment
21%	With benzotriazol-1-ol; diisopropyl-carbodiimide; In DMF (N,N-dimethyl-formamide); at 20℃;	A solution of <strong>[23361-28-6]Boc-Val-Pro-OH</strong> (94.5 mg, 0,30 mmmol) in DIMETHYLFORMAMIDE (1.5 mL), was successively treated, at room temperature, with 1-HYDROXIBENZOTRIAZOL (40.5 mg, 0.30 MMOL), N, N-DIISOPROPYLCARBODIIMIDE (46.7 ßL, 0.30 MMOL) and Ara-C (60.9 mg, 0.25 MMOL). The stirring was continued until complete disappearance of the starting material (overnight stirring). Then, the solvent was evaporated, the residue was dissolved in ethyl acetate and washed with citric acid (10%), NAHCO3 (10%) and brine. The organic layer was dried (NA2SO4) and evaporated to give a residue that was purified by CCTLC on the chromatotron with DICHLOROMETHANE : METANOL (20 : 1) to yield Ara-C-dipeptide (A) (21 % yield)

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 559 - 572
[2]Patent: WO2004/98644,2004,A1 .Location in patent: Page/Page column 58-59

44
[ 791111-79-0 ]
[ 147-94-4 ]
[ 791111-72-3 ]

Yield	Reaction Conditions	Operation in experiment
22%	With benzotriazol-1-ol; diisopropyl-carbodiimide In DMF (N,N-dimethyl-formamide) at 20℃;	13 A solution of Z-Val-Pro-Val-Pro-OH (134.4 mg, 0,24 MMOL) in DIMETHYLFORMAMIDE (1.5 mL), was successively treated at room temperature with 1-HYDROXIBENZOTRIAZOL (33.3 mg, 0.24 mmol), N, N'- diisopropylcarbodiimide (38. 4, UL, 0.24 MMOL) and Ara-C (50 mg, 0.20 MMOL). The stirring was continued until complete disappearance of the starting material (overnight). Then, the solvent was evaporated, and the residue was dissolved in ethyl acetate and washed with citric acid (10%), NaHCOs (10%) and brine. The organic layer was dried (NA2SO4) and evaporated to dryness leaving a residue that was purified by CCTLC on the chromatotron with dichloromethane : metanol (20: 1) to give D (22 % yield)

Reference： [1]Current Patent Assignee: KATHOLIEKE UNIVERSITEIT LEUVEN - WO2004/98644, 2004, A1 Location in patent: Page/Page column 59

45
[ 19449-30-0 ]
[ 147-94-4 ]
[ 908340-60-3 ]

Yield	Reaction Conditions	Operation in experiment
85%	In N,N-dimethyl-formamide	9 Ara-C (85 mg, 0.35 mmol) in DMF (2 mL) is reacted with dibutylformamide dimethyl acetal (0.9 g, 5.14 mmol). Evaporation and crystallization from ethanol-ethyl acetate gave N4-[(Dibutylamino)methylene]arabinocytidine (104 mg, 85%).

Reference： [1]Current Patent Assignee: MERCK & CO INC - US2006/198824, 2006, A1 Location in patent: Page/Page column 28

46
[ 908340-75-0 ]
[ 147-94-4 ]
[ 908340-65-8 ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide at 20℃;	14 Ara-C (500 mg, 2.05 mmol) in DMF (10 mL) is reacted with N-(dimethoxy methyl)dimethyl piperidine (2.7 g, 16.8 mmol) for several hours at room temperature. The contents are evaporated and the residue chromatographed over silica gel using 1-6% MeOH in CH2Cl2. The desired fractions are collected and evaporated. The foam obtained is recrystallized from a mixture of ethanol, CH2Cl2, and ethyl acetate to give N4-[Dimethylpiperidinomethylene]arabinocytidine.

Reference： [1]Current Patent Assignee: MERCK & CO INC - US2006/198824, 2006, A1 Location in patent: Page/Page column 29

47
[ 147-94-4 ]
N-allyloxycarbonyl arabinosylcytosine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With pyridine In 1,4-dioxane; methanol; chloroform	N-allyloxycarbonyl Arabinosylcytosine (7) N-allyloxycarbonyl Arabinosylcytosine (7) Diallyl pyrocarbonate (86.8 mg, 0.452 mmol) was diluted in 1,4-dioxane (5 mL) and added to a solution of arabinosylcytosine (100 mg, 1.61 mmol) dissolved in ddH2O (1 mL) at room temperature. After the reaction mixture was refluxed for two hours in an oil bath, the solvent was removed under reduced pressure and co-evaporated the white residue with anhydrous pyridine (3*5mL). Purified by silica gel chromatography (15% MeOH in CHCl3) to give 7 (91 mg, 76% based on recovered starting material) as a white foam. 1H NMR (DMSO6): d 10.75 (br, 1H); 8.04 (d, 1H, J=7.51 Hz); 7.00 (d, 1h, J=7.51 Hz); 6.04 (d, 1H, J=3.85 Hz); 5.95 (m, 1H); 5.46 (m, 1H); 5.39 & 5.25 (dd, 1H, J=1.47 & 35.34 Hz); 5.32 & 5.21 (dd, 1H, J=1.1 & 23.32 Hz), 5.11 (m, 1H); 4.62 (d, 2H, J=5.31 Hz); 4.04 (m, 1H); 3.91 (m, 1H); 3.81 (m, 1H); 3.60 (m, 2 H). HPLC (Gradient 0% to 70% CH3CN/H2O [0.1% TFA] over 30 min): 12.18 min; 99%. ESI MS (low resolution): (M+H)=328 m/z; MW=327 for C13H17N3O7.

Reference： [1]Current Patent Assignee: PURDUE UNIVERSITY SYSTEM - US2002/4594, 2002, A1

48
[ 104292-51-5 ]
[ 147-94-4 ]
N4-(1-(4-nitrophenyl)ethoxycarbonyl)-1-β-D-arabinofuranosylcytosine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
22%	With sodium hydrogencarbonate In 2,4-dichlorophenoxyacetic acid dimethylamine for 168h;	11 Cytarabine (735 mg, 3.0 mmol), l-chlorocarbonyloxy-l-(4-nitrophenyl)ethane (2.29 g, 10.0 mmol), sodium bicarbonate (882 mg, 10.5 mmol) and DMA (20 mL) were stirred for 7 days. The suspension was filtered and the filtrate concentrated in vacuo. The solid was dissolved in methanol and then adsorbed on to flash silica. Column chromatography, eluting with ethyl acetate then 10% methanol / ethyl acetate, produced a yellow oil. The oil was triturated with acetonitrile; the suspension was filtered, and the solid was washed with ice-cold acetonitrile then dried at the pump. The title compound was obtained as a cream powder (292 mg, 22%); mpt=144- 146°C; TLC Rf=O-I, ethyl acetate. 1H NMR (270 MHz, DMSO) δ 10.86 (IH, s, NH), 8.27 (2H, d, J=8.1, ArH), 8.04 (IH, d, J=8.1, NCH=CH), 7.68 (2H, d, J=8.1, ArH), 6.95 (IH, d, J=8.1, NCH=CH), 6.04 (IH, d, J=5.4, NCHO), 5.95 (IH, q, J=5.4, OCHCH3), 5.49 (2H, m, 2 x OH), 5.05 (IH, t, J=5.4, OH), 4.05 (IH, bs, CHOH), 3.91 (IH, bs, OCHCH2OH), 3.83 (IH, bs, CHOH), 3.59 (2H, t, J=5.4, CH2OH), 1.54 (3H, d, J=5.4, OCHCH3) ppm. l-Chlorocarbonyloxy-l-(4-nitrophenyl)ethane was synthesized as follows:2-(4-Nitroρhenyl)ethanol (1.67 g, 10.0 mmol) in THF (10 mL) was added to phosgene (5.5 mL, 11.0 mmol) and THF (30 mL) at 0°C. The reaction was stirred for 16 h then the solvent was removed in vacuo. The crude chloroformate was used without further purification.

Reference： [1]Current Patent Assignee: GRAY LABORATORY CANCER RESEARCH TRUST; ANGIOGENE PHARMACEUTICALS LIMITED - WO2006/32921, 2006, A1 Location in patent: Page/Page column 39

49
[ 880634-00-4 ]
[ 147-94-4 ]
N4-(5-nitrofuran-2-yl)methoxycarbonyl-1-β-D-arabinofuranosylcytosine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
7%	With sodium hydrogencarbonate In 2,4-dichlorophenoxyacetic acid dimethylamine for 72h;	12 Cytarabine (812 mg, 3.31 mmol), 2-Chlorocarbonyloxymethyl-5-nitrofuran (2.05 g, 10.00 mmol), sodium bicarbonate (980 mg, 11.66 mmol) and DMA (10 mL) were stirred for 72 h. The suspension was filtered and the filtrate concentrated in vacuo to give a solid, which was dissolved in methanol and then adsorbed on to flash silica. Column chromatography, eluting with ethyl acetate then 10% methanol / ethyl acetate, produced an impure oil. Further flash chromatography, eluting with DCM then 5%, 10%, and 15% methanol / DCM, afforded an amber oil. The oil was triturated with ether; the suspension was filtered, and the solid was washed with ether then dried at the pump. The title compound was obtained as a beige powder (95 mg, 7%); mpt=105-107°C; TLC RjHD.18, 10% methanol / ethyl acetate. 1H NMR (270 MHz, DMSO) δ 10.91 (IH, s, NH), 8.07 (2H, s, HarH), 7.70 (IH, s, HarH), 6.98 (IH, s, NCH=CH), 6.04 (IH, s, NCHO), 5.49 (2H, s, 2 x OH), 5.26 (2H, s, HarCH2O), 5.05 (IH, s, OH), 4.10 (IH5 bs, CHOH), 3.91 (IH, bs, OCHCH2OH), 3.82 (IH, bs, CHOH), 3.59 (2H, m, CH2OH) ppm.2-Chlorocarbonyloxymethyl-5-nitrofuran was prepared as follows: 2-Hydroxymethyl- 5-nitrofuran (1.43 g, 10.0 mmol) in THF (10 mL) was added to phosgene (5.5 mL, 11.0 mmol) and THF (30 mL) at O0C. The reaction was stirred for 16 h then the solvent was removed in vacuo. The crude chloroformate was used without further purification.

Reference： [1]Current Patent Assignee: GRAY LABORATORY CANCER RESEARCH TRUST; ANGIOGENE PHARMACEUTICALS LIMITED - WO2006/32921, 2006, A1 Location in patent: Page/Page column 40

50
[ 147-94-4 ]
[ 930285-79-3 ]
N4-(5-methoxy-1,2-dimethyl-4,7dioxoindol-3-yl)methoxycarbonyl-1-β-D-arabinofuranosylcytosine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate In 2,4-dichlorophenoxyacetic acid dimethylamine at 20℃; for 24h;	13 3-Hydroxvmethyl-5-methoxy-l,2-dimethylindole-4,7-dione (150 mg, 0.64 mmol) was dissolved in pyridine (0.5 mL) and the solution cooled to 00C. A solution of 4- nitrophenylchloroforniate (200 mg, 1 mmol) in pyridine (0.5 mL) was then added drop-wise and the solution warmed to 20°C over 1 h. The solution was partitioned (ethyl acetate / brine) and extracted further with ethyl acetate, dried and evaporated to dryness. The crude 4-nitrophenylcarbonate was dissolved in DMA (2 mL) together with cytarabine (500 mg, 2.05 mmol) and sodium bicarbonate (500 mg, 5.95 mmol). The solution was stirred at 2O0C for 24 h and then evaporated to dryness at 30°C, dissolved in methanol, filtered and absorbed onto silica gel (2.5 g). The material was then purified by flash chromatography, eluting with ethyl acetate followed by 10 % methanol / ethyl acetate to afford the title compound as an orange solid (20 mg, 10 %); mpt=>250°C (dec). TLC Rf=0.2, (10 % methanol / ethyl acetate). LC-RT 2.16 min (TFA20-50%); MS m/z 235/220/151. 1H NMR (500 MHz, DMSO) δ 10.55 (IH, s, NH)5 8.05 (IH, s, NCH=CH), 7.00 (IH, s, NCH=CH)3 6.05 (IH, s, NCHO), 5.79 (IH, s, HarH), 5.54 (2H, s, 2 x OH), 5.25 (s, 2H, HarCH2OCONH), 5.10 (IH, s, OH), 4.05 (IH, bs, CHOH), 3.90 (s, 3H, HarOCH3), 3.91 (IH, bs, OCHCH2OH), 3.85 (s, 3H5 HarNCHs), 3.84 (IH, bs, CHOH), 3.61 (2H, m, CH2OH), 2.28 (3H5 s, HarCH3) ppm.

Reference： [1]Current Patent Assignee: GRAY LABORATORY CANCER RESEARCH TRUST; ANGIOGENE PHARMACEUTICALS LIMITED - WO2006/32921, 2006, A1 Location in patent: Page/Page column 41

51
[ 592-34-7 ]
[ 147-94-4 ]
[ 81691-73-8 ]

Yield	Reaction Conditions	Operation in experiment
50%	With triethylamine In methanol; ethanol; ISOPROPYLAMIDE; water; Petroleum ether	1 EXAMPLE 1 EXAMPLE 1 To a solution of 4.0 g of arabinofuranosylcytosine dissolved in 50 ml of dimethylacetamide, there are added 5.0 g of triethylamine and 3.37 g of butyloxycarbonyl chloride. The reaction is carried out by stirring the mixture at room temperature for 3 hours. After completion of the reaction, the solvent is evaoprated under reduced pressure. The residue is diluted with 20 ml of ethanol, followed by addition of 150 ml of petroleum ether. After the mixture is stirred at 0° to 5° C. for one hour, the resultant precipitates are collected by filtration. The precipitates are dissolved in 15 ml of methanol and then 100 ml of water is added to the resultant solution. The mixture is left to stand in a refrigerator and the precipitated crystals are filtered to give 2.8 g of N4 -butyloxycarbonyl-1-β-D-arabinofuranosylcytosine (Yield:50%). Elemental analysis for C14 H21 H3 O7: Calcd. (%): C 48.98; H 6.17; N 12.24; Found (%): C 49.17; H 6.32; N 12.30. NMR (in DMSO-d6) δ value: --CH3 0.94, --(CH2)2 -- 1.0-2.0, H2 '-H5 ' 3.4-4.4, --OCH2 4.14, H1 ' 6.08, H5 7.04, H6 8.08

Reference： [1]Current Patent Assignee: ASAHI KASEI CORPORATION - US4367332, 1983, A

52
chloroform-n-hexane [ No CAS ]
[ 40256-44-8 ]
[ 147-94-4 ]
[ 81691-82-9 ]

Yield	Reaction Conditions	Operation in experiment
30%	With sodium bicarbonate In ice-water; ISOPROPYLAMIDE; toluene	10 EXAMPLE 10 EXAMPLE 10 In 130 ml of dimethylacetamide, 7.3 g of arabinofuranosylcytosine is dissolved and to the resultant solution is added 40 ml of a toluene solution containing 7.56 g of sodium hydrogen carbonate and 7.0 g of undecyloxycarbonyl chloride. The mixture is then stirred at room temperature for 3 hours. After the reaction is over, the solvent is removed under reduced pressure and ice-water is added to the residue, whereby the cyrstals are precipitated. The crystals are filtered and washed with water, followed by sufficient drying. Recrystallization of the product is performed twice, using 80 ml of chloroform-n-hexane, to give 4.0 g of N4-undecyloxycarbonyl-1-β-D-arabinofuranosylcytosine (Yield:30%). Elemental analysis for C21 H35 N3 O7: Calcd. (%): C 57.03; H 8.14; N 9.50; Found (%): C 56.88; H 8.31; N 9.37. NMR(DMSO-d6) δ value: --CH3 0.86, --(CH2)9 -- 1.1-1.8, H2 '-H5 ' 3.5-4.3, --OCH2 -- 4.16, H1 ' 6.14, H5 7.08, H6 8.12.

Reference： [1]Current Patent Assignee: ASAHI KASEI CORPORATION - US4367332, 1983, A

53
[ 6092-54-2 ]
[ 147-94-4 ]
[ 81691-76-1 ]

Yield	Reaction Conditions	Operation in experiment
47%	With pyridine; In ISOPROPYLAMIDE; water;	EXAMPLE 4 To a solution of 4.0 g of arabinofuranosylcytosine dissolved in 50 ml of dimethylacetamide, there are added 3.0 g of pyridine and 4.06 g of n-hexylchloroformate. The reaction is carried out by stirring the mixture at room temperature for 3 hours. After the reaction is over, dimethylacetamide is evaporated under reduced pressure. The residue is diluted with 100 ml of cold water and the mixture is stirred under ice-cooling for one hour. The precipitated solids are filtrated and dried. The resultant white powders are washed with ethyl ether to obtain 2.9 g of N4 -hexyloxycarbonyl-1-beta-D-arabinofuranosylcytosine (Yield:47%). Elemental analysis for C16 H25 N3 O7: Calcd. (%): C 51.75; H 6.79; N 11.31; Found (%): C 51.53; H 6.88; N 11.26. NMR(DMSO-d6) delta value: --CH3 0.88, --(CH2)3 -- 1.1-1.9, H2 '-H5 ' 3.3-4.3, --OCH2 -- 4.12, H1 ' 6.10, H5 7.04, H6 8.08

Reference： [1]Patent: US4367332,1983,A

54
[ 33758-34-8 ]
3,3,3-trichloropropanenitrile [ No CAS ]
[ 147-94-4 ]
[ 81691-78-3 ]

Yield	Reaction Conditions	Operation in experiment
40%	With sodium bicarbonate In ISOPROPYLAMIDE; water	6 EXAMPLE 6 EXAMPLE 6 To a solution of 4.0 g of arabinofuranosylcytosine dissolved in 50 ml of dimethylacetamide, there are added 4.15 g of sodium hydrogen carbonate and 4.41 g of heptylchloroformate. The resultant mixture is allowed to react under stirring at room temperature for 3 hours. After the reaction, dimethylacetamide is removed under reduced pressure and 150 ml of cold water is added to the residue. After the mixture is stirred for 2 hours, the solids are collected by filtration and dried. Recrystallization of the white powders obtained is performed twice, using 200 ml and 150 ml of a mixture of chloroform-acetonitrile (1:1), to give 2.5 g of N4 -heptyloxycarbonyl-1-β-D-arabinofuranosylcytosine (Yield:40%). Elemental analysis for C17 H27 N3 O7: Calcd. (%): C 52.98; H 7.06; N 10.90; Found (%): C 53.13; H 6.87; N 10.85. NMR(DMSO-d6) δ value: --CH3 0.88, --(CH2)5 -- 1.1-1.9, H2 '-H5 ' 3.4-4.3, --OCH2 -- 4.16, H1 ' 6.12, H5 7.08, H6 8.12

Reference： [1]Current Patent Assignee: ASAHI KASEI CORPORATION - US4367332, 1983, A

55
[ 57045-82-6 ]
[ 147-94-4 ]
[ 81691-80-7 ]

Yield	Reaction Conditions	Operation in experiment
37%	With sodium bicarbonate In ISOPROPYLAMIDE; water	8 EXAMPLE 8 EXAMPLE 8 In 120 ml of dimethylacetamide, 6.0 g of arabinofuranosylcytosine is dissolved and to the resultant solution are added 4.15 g of sodium hydrogen carbonate and 7.66 g of nonyloxycarbonyl chloride. The mixture is then allowed to react under stirring at 20 to 25° C. for 2 hours. After the reaction, the solvent is removed under reduced pressure and the residue is dissolved in a small amount of ethanol. Water is then added to the resultant solution and the precipitated solids are collected by filtration, followed by drying. The white powders obtained are washed thoroughly with ethyl ether to obtain 3.8 g of N4 -nonyloxycarbonyl-1-β-D-arabinofuranosylcytosine (Yield:37%). Elemental analysis for C19 H31 N3 O7: Calcd. (%): C 55.19; H 7.56; N 10.16; Found (%): C 55.04; H 7.66; N 10.14. NMR(DMSO-d6) δ value: --CH3 0.84, --(CH2)7 -- 1.0-1.8 H2 '-H5 ' 3.5-4.3, --OCH2 -- 4.10, H1 ' 6.06, H5 6.98, H6 8.02

Reference： [1]Current Patent Assignee: ASAHI KASEI CORPORATION - US4367332, 1983, A

56
[ 848046-57-1 ]
[ 147-94-4 ]
[ 848046-62-8 ]

Yield	Reaction Conditions	Operation in experiment
	With ethylene dichloride hydrochloride; benzotriazol-1-ol In pyridine at 20 - 40℃;	17.8 A mixture of 7b (0.67 g, 1.4 mmol), ara-C (1.36 g, 5.6 mmol), HOBT (0.76 g, 5.6 mmol) and EDC-HCl (2.15 g, 11.2 mmol) in anhydrous pyridine (35 ml) was stirred at room temperature for 2h followed by stirring at 40 0C overnight. The solvent was removed in vacuo and the residue was dissolved in CH2Cl2 (50 ml) followed by extraction with water (3 x 30 ml) and 0.1 M HCl (2 x 30 ml) . The organic phase was dried over anhydrous MgSO4 and evaporated in vacuo. The residue was purified by flash chromatography (5-10 % MeOH in CH2Cl2) to give white crystalline material. Yield: 0.35 g.1H NMR (CDCl3) δ 9.35-9.01 (m, IH), 8.59 (m, IH), 8.15 (m, IH), 7.69 (m, IH), 7.28 (m, 6H), 6.75 (d, IH), 6.23 (t, IH), 6.16 (t,lH), 5.90-5.74 (m, IH), 5.25 (s, IH), 4.84 (m, IH), 4.59 (s, IH), 4.33 (s, IH), 4.15 (s, IH), 3.92-3.67 (m, 2H), 3.35-3.25 (m, IH), 3.20-3.12 (m, IH), 2.88 (s, 2H), 2.54-2.41 (m, 3H), 2.23 (d, 3H), 1.58-1.44 (m, 6H) , 1.38 (s, 9H) ;13C NMR δ 173.59, 172.30, 162.45, 156.40, 156.03, 150.23, 149.99, 147.04, 138.60, 137.13, 136.65, 136.42, 133.71, 133.31, 129.92, 129.70, 129.01, 127.52, 124.28, 123.02, 96.95, 89.22, 86.50, 80.63, 74.77, 62.36, 55.53, 50.71, 40.02, 38.33, 32.57, 31.93, 28.71, 25.82, 20.56.

Reference： [1]Current Patent Assignee: DRUG DISCOVERY LABORATORY - WO2006/30217, 2006, A2 Location in patent: Page/Page column 31; 36-37

57
[ 7075-11-8 ]
[ 147-94-4 ]
[ 18354-06-8 ]

Reference： [1]Journal of Organic Chemistry,2008,vol. 73,p. 4123 - 4130

58
M-PEOZ-O-CH₂-CO₂-NHS [ No CAS ]
[ 147-94-4 ]
M-PEOZ-Ara-C [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With pyridine at 0 - 20℃; for 72h;	35 M-PEOZ-O-CH2-CO2-NHS (M-PEOZ-SCM 5000) (180 mg, 0.034 mmol) was dissolved in 11 mL of pyridine and added to a solution of cytosine arabinose (Ara-C) (5.7 mg, 0.023 mmol), previously dissolved in 5 mL of anhydrous pyridine at 0 C. The resulting solution stirred for 72 hours at room temperature. Reverse phase HPLC (C- 18 column) showed that reaction was complete. After evaporation of the solvent, the product was dissolved in methylene chloride (5 mL) and added drop by drop into 150 mL ether. The precipitate was collected by centrifugation at 4 °C and dried under vacuum. Yield 150 mg, 80%. NMR showed the usual peaks of the M-PEOZ backbone (above) plus the pyrimidine protons of Ara- C at 7.31, 7.67, 8.16, and 8.62 ppm. Exposure of the conjugate to pH 8 buffer showed that Ara-C is slowly released (15% after 24 hours), so the conjugate can be regarded as a prodrug.

Reference： [1]Current Patent Assignee: SERINA THERAPEUTICS, INC. - WO2008/106186, 2008, A2 Location in patent: Page/Page column 61

59
[ 100-51-6 ]
[ 147-94-4 ]
[ 848046-70-8 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: arabinosyl cytosine With trimethyl phosphite; trichlorophosphate at -10 - 0℃; for 4h; Stage #2: benzyl alcohol at 4℃; for 48h;	19 POC13 (0.5 ml) was added to a mixture of ara-C (0.73 g, 3 mmol) and trimethyl phosphate (15 ml) AT-10 °C. The reaction mixture was stirred at 0 °C for 4h before benzylalcohol (15 mmol) was added. After 48h at 4 °C the reaction mixture was poured into H20 (250 ml) containing NAHCO3 (1 g). The reaction was evaporated in vacuo and dissolved in MeOH (5 ml). Insoluble material was filtred and the filtrate was added diethyl ether to precipitate the product as white crystalline material. H NMR (CDC13) 5 9.40-9. 09 (d, 1H), 7.90 (d, 7. 1 Hz, 1H), 7.30-7. 15 (m, 5H), 6.05 (d, 3.0 Hz, 1H), 4.35-3. 64 (m, 7H), 3.66 (d, 11.0 HZ, 1H), 3.43 (S, 2H), 3.40 (S, 2H), 2.84 (t, 2H); I-3C NMR 5 162.03, 150.79, 144.96, 138.86, 129.26, 128. 56, 126.45, 93.18, 87.05, 84.35, 76.19, 74.87, 65.67, 64.74, 54.40, 52.28, 36.97.

Reference： [1]Current Patent Assignee: DRUG DISCOVERY LABORATORY - WO2005/25552, 2005, A2 Location in patent: Page/Page column 34-35

60
[ 133081-26-2 ]
[ 147-94-4 ]
[ 1187772-87-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 4764 - 4767

61
[ 17445-33-9 ]
[ 147-94-4 ]
[ 1203578-13-5 ]

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 559 - 572

62
[ 41624-92-4 ]
[ 147-94-4 ]
C₁₈H₂₇N₃O₈ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl acetamide at 30℃; for 22h;	12 Example 12:The hydroxamic acid derivatives with P represented bysynthesized according to the synthetic scheme below:1 to 3: To a solution of Cytarabine (36 mmol) in 150 mL dimethylacetamide (DMA) was added a solution of compound 2 (42 mmol) in 50 mL DMA, and the mixture was stirred at 30 degree C for 22h. The solvent was evaporated at high vacuum and the residue was treated with hot ethyl acetate and filtered. The crude product was treated with 2 M NaHCO3 solution, filtered off and purified by silica gel column t afford compound 3.

Reference： [1]Current Patent Assignee: PURDUE PHARMA L.P. - WO2010/85377, 2010, A2 Location in patent: Page/Page column 50

63
[ 100-51-6 ]
[ 147-94-4 ]
ara-C 5'-O-(1-benzoyl)phosphate sodium salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: arabinosyl cytosine With trimethyl phosphite; trichlorophosphate at 0℃; for 4h; Stage #2: benzyl alcohol at 4℃; for 48h; Stage #3: With sodium hydrogencarbonate In water	19 POCl3 (0.5 ml) was added to a mixture of ara-C (0.73 g, 3 mmol) and trimethyl phosphate (15 ml) at -10 "C. The reaction mixture was stirred at 0 "C for 4h before benzylalcohol (15 mmol) was added. After 48h at 4 "C the reaction mixture was poured into H2O (250 ml) containing NaHCO3 (1 g) . The reaction was evaporated in vacuo and dissolved in MeOH (5 ml) . Insoluble material was filtred and the filtrate was added diethyl ether to precipitate the product as white crystalline material.1H NMR (CDCl3) δ 9.40-9.09 (d, IH), 7.90 (d, 7.1 Hz, IH), 7.30-7.15 (m, 5H), 6.05 (d, 3.0 Hz, IH), 4.35-3.64 (m, 7H), 3.66 (d, 11.0 Hz, IH), 3.43 (s, 2H), 3.40 (s, 2H), 2.84 (t, 2H);13C NMR δ 162.03, 150.79, 144.96, 138.86, 129.26, 128.56, 126.45, 93.18, 87.05, 84.35, 76.19, 74.87, 65.67, 64.74, 54.40, 52.28, 36.97.

Reference： [1]Current Patent Assignee: DRUG DISCOVERY LABORATORY - WO2006/30217, 2006, A2 Location in patent: Page/Page column 43-44

64
[ 75-44-5 ]
[ 20898-85-5 ]
[ 147-94-4 ]
N4-(5-nitrothien-2-yl)methoxycarbonyl-1-β-D-arabinofuranosylcytosine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
8%	Stage #1: arabinosyl cytosine With pyridine; chloro-trimethyl-silane In dichloromethane at 0℃; for 2h; Stage #2: phosgene; (5-nitrothiophen-2-yl)methanol In dichloromethane; toluene for 18h;	2 Chlorotrimethylsilane (76μL, 0.60mmol) was added to Ara-C (48mg, 0.20mtnol), pyridine (97μL, 1.20mmol) and DCM (0.3mL) at O0C. After 2h, 5-nitrothien-2- ylmethanol (48mg, 0.30mmol) in DCM (0.2mL) was added, followed by dropwise addition of phosgene solution (0.2mL, 0.24mmol, 2M in toluene). The reaction was stirred for a further ISh. The crude mixture was partitioned (ethyl acetate and brine), the aqueous phase was extracted (ethyl acetate); the organic phases were combined, washed (water then brine) then adsorbed on to flash silica in vacuo. Flash chromatography, eluting with DCM then 2%, 5%, and 10% methanol / ethyl acetate, afforded the title compound as a white wax (7mg, 8%); TLC Rf=0.3, 10% methanol / ethyl acetate. 1H NMR (500Mhz, DMSO-d6, δ) 10.98 (IH, s, NH), 8.10 (2H, s,HarH), 7.35 (IH, s, HarH), 7.07 (IH, s, NCH=CH), 6.08 (IH, s, NCHO), 5.51 (2H, s, 2 x OH), 5.43 (2H, s, HarCH2O), 5.05 (IH, s, OH), 4.10 (IH, bs, CHOH), 3.95 (IH, bs, OCHCH2OH), 3.85 (IH, bs, CHOH), 3.61 (2H, m, CH2OH) ppm.

Reference： [1]Current Patent Assignee: GRAY LABORATORY CANCER RESEARCH TRUST; ANGIOGENE PHARMACEUTICALS LIMITED - WO2006/32921, 2006, A1 Location in patent: Page/Page column 30-31

65
[ 56882-00-9 ]
[ 147-94-4 ]
[ 915978-85-7 ]

Yield	Reaction Conditions	Operation in experiment
56%	Stage #1: (4E,8E,12E,16E)-4,8,13,17,21-pentamethyl-4,8,12,16,20-docosapentaenoic acid With chloroformic acid ethyl ester; triethylamine In tetrahydrofuran at 0℃; for 0.333333h; Inert atmosphere; Stage #2: arabinosyl cytosine In tetrahydrofuran; N,N-dimethyl-formamide at 0 - 20℃; for 72h; Inert atmosphere;

Reference： [1]Location in patent: experimental part Sarpietro, Maria Grazia; Ottimo, Sara; Giuffrida, Maria Chiara; Rocco, Flavio; Ceruti, Maurizio; Castelli, Francesco [International Journal of Pharmaceutics, 2011, vol. 406, # 1-2, p. 69 - 77]

66
[ 81-25-4 ]
[ 147-94-4 ]
[ 1353348-31-8 ]

Yield	Reaction Conditions	Operation in experiment
78%	Stage #1: cholic acid With triethylamine; isobutyl chloroformate In N,N-dimethyl-formamide at -15℃; for 0.25h; Inert atmosphere; Stage #2: arabinosyl cytosine With triethylamine In N,N-dimethyl-formamide at -15 - 20℃; for 0.5h; Inert atmosphere;	2.2.1 (R)-N-(1-((3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-furan-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)-(R)-4-((3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-3,7,12-trihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl) pentanamide (2) To a stirred solution of cholic acid (0.49g, 1.2mmol) in anhydrous N, N-dimethylformamide (DMF, 10mL), triethylamine (0.20mL, 1.5mmol) was added under nitrogen atmosphere. The mixture was cooled to -15°C and a solution of isobutyl chloroformate (0.20mL, 1.5mmol) was added dropwise. The mixture was stirred at -15°C for 15min and a solution of cytarabine (0.24g, 1.0mmol) and triethylamine (0.20mL, 1.5mmol) in 10mL anhydrous DMF was added dropwise to the reaction mixture at the same temperature. The reaction mixture was continually stirred for 30min at room temperature. After the reaction had been completed, the solvent was removed by RE-52A rotary evaporation (Shanghai Yarong Biochemical Instrument Plant, China). The residue was then purified by chromatography on silica gel eluting with dichloromethane/methanol (10:1) to obtain pure compound 2 as an amorphous white solid (0.50g, 78%). 1H NMR(300MHz, d6-DMSO, δ ppm): 10.8 (s, 1H), 8.04 (d, 1H, J=7.5Hz), 7.20 (d, 1H, J=7.5Hz), 6.05 (d, 1H, J=3.9Hz), 5.47(d, 2H, J=3.0), 5.05 (t, 2H), 4.31 (d, 1H, J=3.9Hz), 4.09 (d, 1H, J=3.3), 3.98 (d, 1H, J=3.3), 3.78 (s, 1H), 3.61 (s, 1H), 3.18 (t, 1H), 2.51-1.21 (m, 24H), 1.15 (d, 2H, J=7.2Hz) 0.93 (d, 3H, J=6.2Hz), 0.80 (s, 3H), 0.59 (s, 3H). 13C NMR (75MHz, d6-DMSO, δ ppm): 174.4, 162.3, 154.6, 146.7, 94.5, 87.0, 85.8, 76.2, 74.7, 71.1, 70.5, 66.4, 61.0, 46.3, 45.8, 41.6, 41.4, 35.4, 35.3, 34.9, 34.5, 33.8, 31.0, 30.5, 28.6, 27.3, 26.3, 22.9, 22.7, 17.1, 12.4. MS (ESI) (m/z): calcd for C33H51N3O9: m/z 634.2 [M+H]+, 656.2 [M+Na]+.
75%	Stage #1: cholic acid With chloroformic acid ethyl ester; triethylamine In N,N-dimethyl-formamide at -15℃; for 0.333333h; Stage #2: arabinosyl cytosine In N,N-dimethyl-formamide at -15 - 20℃;

Reference： [1]Zhang, Dong; Li, Dongpo; Shang, Lei; He, Zhonggui; Sun, Jin [International Journal of Pharmaceutics, 2016, vol. 511, # 1, p. 161 - 169]
[2]Location in patent: experimental part Chen, Dan-Qi; Wang, Xin; Chen, Lin; He, Jin-Xue; Miao, Ze-Hong; Shen, Jing-Kang [Acta Pharmacologica Sinica, 2011, vol. 32, # 5, p. 664 - 672]

67
[ 105-38-4 ]
[ 147-94-4 ]
[ 881848-60-8 ]
3'-O-propionyl ara-C [ No CAS ]
[ 75-07-0 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In water at 30℃; for 24h; Green chemistry; Enzymatic reaction; Overall yield = 57.37 %; regioselective reaction;	General procedure of whole-cell acylation of ara-C: 2 ml organic solvents containing 20 mM ara-C, 600 mM VP, 4% water and 50 mg/ml freeze-dried Aspergillus oryzae 3.5232 (Collection No.3.5232) were incubated by shaking (140 rpm) at a fixed temperature for 24 h. Aliquots were withdrawn at specified time intervals from the reaction mixture, and then diluted 100 times with water-methanol prior to HPLC analysis. To structurally characterize the product of the whole-cell catalyzed acylation of ara-C with VP, the reaction was scaled up. Upon completion of the reaction, the reaction mixture was centrifuged to remove the cell masses, isolated, and purified by half-preparation HPLC with a semi-preparation column. The acquisition was concentrated to about 1 mL by vacuum rotary evaporation. After crystallization under 4 °C, two products were obtained and then determined by 13C NMR (Bruker AVANCE Digital 400 MHz Nuclear Magnetic Resonance Spectrometer, Bruker Co., Germany) at 100 MHz. The ESI-MS spectra of the product were recorded on a Thermo LCQ DECA XP Plus ESI Mass Spectrometer with a spray voltage of 4.5 kV (Thermo Finnigan, USA). All the experiment was repeated twice.

Reference： [1]Yang, Mei-Yan; Wu, Hui; Lu, Zhi-Hong; Li, Xiao-Feng; Lai, Fu-Rao; Zhao, Guang-Lei [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 15, p. 3377 - 3380]

68
[ 76-83-5 ]
[ 147-94-4 ]
[ 7075-13-0 ]

Yield	Reaction Conditions	Operation in experiment
95.2%	With pyridine at 20℃; for 20h; Inert atmosphere; regioselective reaction;	1 4.1. 5′-Tr-cytarabine Triphenylmethyl chloride (153.3 g, 0.55 mol) was added in portions to an ice-cooled suspension of cytarabine (1, 121.6 g, 0.50 mol) in anhydrous pyridine (800 mL). It was stirred at room temperature for 20 h until the completion of the reaction detected by TLC, then concentrated under reduced pressure to remove pyridine. The residual was diluted with ethanol (250 mL), poured into ice-water (2.0 L) with stirring. The formed solid was filtrated and washed with water to give the crude, which was recrystallized from ethyl acetate to afford the product (231.1 g, 95.2%) as white solid. Mp 210-213 °C; 1H NMR (300 MHz, DMSO-d6): δ 3.11-3.15 (m, 2H), 3.81-3.88 (m, 3H), 5.33 (d, J=4.8 Hz, 1H), 5.42 (d, J=4.4 Hz, 1H), 5.55 (d, J=7.4 Hz, 1H), 6.05 (d, J=4.4 Hz, 1H), 7.00 (brs, 2H), 7.26-7.33 (m, 15H), 7.42 (d, J=7.4 Hz, 1H); ESI-MS(m/z)=486.2[M+H]+, 508.3[M+Na]+, 524.2[M+K]+.
95.2%	With pyridine In water at 30℃; for 22h; Inert atmosphere;	1.1 Example 1: S-2-Amino-3-methylbutanoic acid 2 - {(2R, 3S, 4S, 5R) -5- [4-amino-2-oxo-1 (1H)Yl] -3,4-dihydroxytetrahydrofuryl} methyl ester hydrochloride (cytosine 5'-position L-valinate, I1a) Step 1: argon protection, cold water cooling,willTrichloromethyl chloride 256.5 g (0.92 mol)Slowly addTo arabinoside (VII1) 194.6 g (0.80 mol)And anhydrous pyridine 1500mL of the mixture,Note that the reaction system is sufficiently stirred by mechanical agitation,The feed rate is controlled so that the added material is gradually dispersed or dissolved in the system.Plus finished, continue to stir 2h,And then slowly heated to 30 ° C and continue to respond for 20h,TLC detection reaction is completed.Concentration under reduced pressure to recover the reaction system of pyridine,And 300 mL of absolute ethanol was added to the residue to sufficiently disperse the contents.The mixture was slowly poured into ice water (5.0 L), and the mixture was rapidly stirred to precipitate a white solid.Filter, washed, dried, pale yellow crude 480.5g.The crude product was recrystallized from ethyl acetate (1000 mL), suction filtered,The filtrate cools and gradually precipitates a white solid. Placed overnight, suction filter,dry,A white solid (VI1) of 462.2 g, yield

Reference： [1]Liu, Jia-An; Guo, Xiao-Peng; Liang, Shuang; An, Fei; Shen, Hong-Yan; Xu, You-Jun [Tetrahedron, 2015, vol. 71, # 9, p. 1409 - 1412]
[2]Current Patent Assignee: SHENYANG PHARMACEUTICAL UNIVERSITY - CN104231008, 2017, B Location in patent: Paragraph 0036; 0037; 0038; 0039; 0040

69
[ 71-30-7 ]
[ 3083-77-0 ]
[ 147-94-4 ]

Yield	Reaction Conditions	Operation in experiment
		A suspension of 1 mM cytosine and 1 mM 1-(B-D-arabinofuranosyl)uracil in aqueous 50 mM MES buffer was thermostated at 50 C. during 30 min. Then, NDT enzyme (SEQ ID NO: 2) was added (0.085 mg/ml) dropwise and the reaction was stirred at 50 C. during at least 1 day under the same conditions. Then, the suspension was hot filtered, and the solid was washed and dried. The aqueous filtrate was partially concentrated, cooled down and filtered. The recovered solid was allowed to partially precipitate and concentrate. Once filtered and washed, the solid was crystallized using a suitable solvent, such as a polar protic or polar aprotic solvent, in combination with water or a suitable apolar solvent.

Reference： [1]Patent: US2016/76070,2016,A1 .Location in patent: Paragraph 0238

70
[ 474-25-9 ]
[ 147-94-4 ]
(4R)-N-(1-((3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-furan-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)-(R)-4-((3R,5S,7R,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	Stage #1: chenodeoxycholic acid With triethylamine; isobutyl chloroformate In N,N-dimethyl-formamide at -15℃; for 0.25h; Inert atmosphere; Stage #2: arabinosyl cytosine With triethylamine In N,N-dimethyl-formamide at -15 - 20℃; for 0.5h; Inert atmosphere;	2.2.1 (R)-N-(1-((3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-furan-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)-(R)-4-((3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-3,7,12-trihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl) pentanamide (2) General procedure: To a stirred solution of cholic acid (0.49g, 1.2mmol) in anhydrous N, N-dimethylformamide (DMF, 10mL), triethylamine (0.20mL, 1.5mmol) was added under nitrogen atmosphere. The mixture was cooled to -15°C and a solution of isobutyl chloroformate (0.20mL, 1.5mmol) was added dropwise. The mixture was stirred at -15°C for 15min and a solution of cytarabine (0.24g, 1.0mmol) and triethylamine (0.20mL, 1.5mmol) in 10mL anhydrous DMF was added dropwise to the reaction mixture at the same temperature. The reaction mixture was continually stirred for 30min at room temperature. After the reaction had been completed, the solvent was removed by RE-52A rotary evaporation (Shanghai Yarong Biochemical Instrument Plant, China). The residue was then purified by chromatography on silica gel eluting with dichloromethane/methanol (10:1) to obtain pure compound 2 as an amorphous white solid (0.50g, 78%).
	Stage #1: chenodeoxycholic acid With triethylamine; isobutyl chloroformate In N,N-dimethyl-formamide at -15℃; for 0.0833333h; Stage #2: arabinosyl cytosine With triethylamine In N,N-dimethyl-formamide at -15 - 20℃; for 2.5h;	1 Preparation of arabinosylcocoodeoxycholic acid conjugate 3.93 g of chenodeoxycholic acid and 1.2 mL of triethylamine were dissolved in 50 mL of dimethylformamide, cooled to -15 ° C, Slowly add isobutyl chloroformate 1. 2mL, 5 minutes after the reaction, adding 2. 43g of cytarabine with triethylamine 1. 2mL dissolved in 20mL Dimethylformamide was added and the reaction was stirred at -15 ° C for 30 minutes and then at room temperature for 2 hours. The reaction solution was filtered to remove To which triethylamine chloride is added and the filtrate is concentrated under reduced pressure to give a crude product. The product was added to 20 mL of dichloromethane Solution, filter to remove the insoluble material, the filtrate mixed with silica gel, silica gel column chromatography, methanol and dichloromethane gradient elution, collecting column layer The precipitate was concentrated to give a white powder of the cytarabine chenodeoxycholic acid conjugate solid.

Reference： [1]Zhang, Dong; Li, Dongpo; Shang, Lei; He, Zhonggui; Sun, Jin [International Journal of Pharmaceutics, 2016, vol. 511, # 1, p. 161 - 169]
[2]Current Patent Assignee: SHENYANG PHARMACEUTICAL UNIVERSITY - CN103788165, 2016, B Location in patent: Paragraph 0030; 0031

71
[ 83-49-8 ]
[ 147-94-4 ]
(4R)-N-(1-((3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-furan-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)-(R)4-((5R,8S,10R,13R,17R)-3,6-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%		General procedure: To a stirred solution of cholic acid (0.49g, 1.2mmol) in anhydrous N, N-dimethylformamide (DMF, 10mL), triethylamine (0.20mL, 1.5mmol) was added under nitrogen atmosphere. The mixture was cooled to -15C and a solution of isobutyl chloroformate (0.20mL, 1.5mmol) was added dropwise. The mixture was stirred at -15C for 15min and a solution of cytarabine (0.24g, 1.0mmol) and triethylamine (0.20mL, 1.5mmol) in 10mL anhydrous DMF was added dropwise to the reaction mixture at the same temperature. The reaction mixture was continually stirred for 30min at room temperature. After the reaction had been completed, the solvent was removed by RE-52A rotary evaporation (Shanghai Yarong Biochemical Instrument Plant, China). The residue was then purified by chromatography on silica gel eluting with dichloromethane/methanol (10:1) to obtain pure compound 2 as an amorphous white solid (0.50g, 78%).
		3.93 g of hyodeoxycholic acid and 1.2 mL of triethylamine were dissolved in 50 mL of dimethylformamide and cooled to -15 C. Slowly add isobutyl chloroformate 1. 2mL, 5 minutes after the reaction, adding 2. 43g of cytarabine with triethylamine 1. 2mL dissolved in 20mL Dimethylformamide was added and the reaction was stirred at -15 C for 30 minutes and then at room temperature for 2 hours. The reaction solution was filtered to remove To which triethylamine chloride is added and the filtrate is concentrated under reduced pressure to give a crude product. The product was added to 20 mL of dichloromethane Solution, filter to remove the insoluble material, the filtrate mixed with silica gel, silica gel column chromatography, methanol and dichloromethane gradient elution, collecting column layer The precipitate was concentrated to give a white powdery cytarabine hyodeoxycholate conjugate solid.

Reference： [1]International Journal of Pharmaceutics,2016,vol. 511,p. 161 - 169
[2]Patent: CN103788165,2016,B .Location in patent: Paragraph 0032; 0033

72
[ 128-13-2 ]
[ 147-94-4 ]
(4R)-N-(1-((3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-furan-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)-(R)-4-((3R,5S,7S,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%		General procedure: To a stirred solution of cholic acid (0.49g, 1.2mmol) in anhydrous N, N-dimethylformamide (DMF, 10mL), triethylamine (0.20mL, 1.5mmol) was added under nitrogen atmosphere. The mixture was cooled to -15C and a solution of isobutyl chloroformate (0.20mL, 1.5mmol) was added dropwise. The mixture was stirred at -15C for 15min and a solution of cytarabine (0.24g, 1.0mmol) and triethylamine (0.20mL, 1.5mmol) in 10mL anhydrous DMF was added dropwise to the reaction mixture at the same temperature. The reaction mixture was continually stirred for 30min at room temperature. After the reaction had been completed, the solvent was removed by RE-52A rotary evaporation (Shanghai Yarong Biochemical Instrument Plant, China). The residue was then purified by chromatography on silica gel eluting with dichloromethane/methanol (10:1) to obtain pure compound 2 as an amorphous white solid (0.50g, 78%).
		3. 93 g of <strong>[128-13-2]ursodeoxycholic acid</strong> and 1.2 mL of triethylamine were dissolved in 50 mL of dimethylformamide and cooled to -15 C. Slowly add isobutyl chloroformate 1. 2mL, 5 minutes after the reaction, adding 2. 43g of cytarabine with triethylamine 1. 2mL dissolved in 20mL Dimethylformamide was added and the reaction was stirred at -15 C for 30 minutes and then at room temperature for 2 hours. The reaction solution was filtered to remove To which triethylamine chloride is added and the filtrate is concentrated under reduced pressure to give a crude product. The product was added to 20 mL of dichloromethane Solution, filter to remove the insoluble material, the filtrate mixed with silica gel, silica gel column chromatography, methanol and dichloromethane gradient elution, collecting column layer The precipitate was concentrated to give a white powder of the cytarabine <strong>[128-13-2]ursodeoxycholic acid</strong> conjugate solid.

Reference： [1]International Journal of Pharmaceutics,2016,vol. 511,p. 161 - 169
[2]Patent: CN103788165,2016,B .Location in patent: Paragraph 0034; 0035

73
[ 4637-24-5 ]
[ 147-94-4 ]
N <SUP>4</SUP>-( N,N-dimethylaminomethylene)cytarabine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	In ethanol at 65℃; for 4h;	1 preparation of N ⁴-( N,N-dimethylaminomethylene)cytarabine The 82mLN, N- dimethylformamide dimethyl acetal (DMF-DMA) and added to a 60g cytarabine 240mL ethanol mixture, the reaction was warmed to 65 °C, four hours after the end of the reaction. The reaction was cooled to room temperature, filtered and the solid was washed with methyl tert-butyl ether (MTBE), 45°C dried in vacuo to give the N4- (the N, of N- dimethylaminomethylene) - cytarabine (N4 -DMA- cytarabine) 69.5 g, as a white solid, yield 96%, purity 99.6% (HPLC).

Reference： [1]Current Patent Assignee: KUNMING JIDA PHARMACEUTICAL CO., LTD. - CN105273023, 2016, A Location in patent: Paragraph 0019

74
[ 147-94-4 ]
[ 2752-65-0 ]
C₄₇H₅₅N₃O₁₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58.9%		Gambogic Acid (500 mg, 0.71 mmol) Cytarabine(156 mg, 0.64 mmol)At room temperature in N, N-dimethylformamide (5.0 mL), And then DIEA (100 mg, 0.78 mmol) was added to the mixture,And HOBT (105 mg, 0.78 mmol),After stirring for 5 minutes, TBTU (249 mg, 0.78 mmol) was added,The temperature was raised to 40 C,Stir for 3 hours.Ethyl acetate (50 ml) was added to the reaction to quench,And then washed with saturated brine (3 x 10 ml)Dried over anhydrous sodium sulfate, and the ethyl acetate was distilled off. Column chromatography [V (methanol): V (dichloromethane) = 1.5: 100]To obtain orange yellow amorphous powder 357mg,The yield was 58.9%

Reference： [1]Patent: CN103265594,2016,B .Location in patent: Paragraph 0041-0044

75
[ 57-10-3 ]
[ 147-94-4 ]
[ 55726-45-9 ]

Yield	Reaction Conditions	Operation in experiment
64.3%	Stage #1: 1-hexadecylcarboxylic acid With chloroformic acid ethyl ester; triethylamine In N,N-dimethyl-formamide for 0.333333h; Inert atmosphere; Cooling with ice; Stage #2: arabinosyl cytosine In N,N-dimethyl-formamide at 20℃; for 72h; Inert atmosphere;	1 Example 1 Synthesis of PA-Ara Prodrug Molecules Analytical balance accurately weighs a certain amount of palmitic acid, dissolves in anhydrous N,N-dimethylformamide (DMF) and places it in doubleIn the flask, triethylamine and ethyl chloroformate were added under stirring, nitrogen protection and reaction under ice bath conditions for 20 minutes. Weigh a certain amountCytarabineSoluble in 5 mL of warm anhydrous DMF,The above reaction solution was slowly dropped under stirring with a molar amount of palmitic acid:triethylamine:ethyl chloroformate:cytarabine=10:11:11:12, and the reaction was returned to room temperature and continued under a nitrogen atmosphere. After 72 hours of reaction, the progress of the reaction was monitored using a thin layer plate. After completion of the reaction, dry DMF was evaporated under reduced pressure and vacuum dried overnight to give a crude product. The crude product was dissolved in ethyl acetate, a little column chromatography silica gel, silica gel column chromatography, twoThe gradient elution of methyl chloride and methanol (100:1-30:1) gave pure PA-Ara as a white solid with a yield of 64.3%.

Reference： [1]Current Patent Assignee: SHANDONG UNIVERSITY - CN107216362, 2017, A Location in patent: Paragraph 0039; 0040

76
[ 71116-61-5 ]
[ 147-94-4 ]
5′-O-α-L-rhamnosyl cytosine arabinoside [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With α-L-rhamnosidase In aq. phosphate buffer at 60℃; for 24h; Enzymatic reaction;	1.2.1; 1.2.2; 1.2.3 2. α-L-rhamnosidase catalyzes the synthesis of cytarabine rhamnoside(1) The concentration of rhamnose is 1.1M and the concentration of cytarabine is 0.5M using sodium phosphate buffer.The amino acid sequence is a reaction system in which the amount of α-L-rhamnosidase shown in SEQ ID NO. 1 is 10 μg/mL;The buffer in the step (1) is a sodium phosphate buffer with a concentration of 100 mM and pH 8.(2) The reaction system prepared in step (1) is reacted in a water bath at 60°C for 24 hours.The reaction was stopped by boiling at 100°C for 5 minutes, centrifuged at 12,000 rpm for 30 minutes, and the supernatant was taken;(3) The supernatant obtained in step (2) is passed through the Agilent 1200 HPLC system.The column was Waters Spherisorb 5.0μm NH2 4.6mm×250mm, flow rate 1.0mL/min, mobile phase acetonitrile: water volume ratio 70:30,UV detection wavelength is 305nm, combined with the same retention time product,The freeze-dried powder is cytarabine rhamnoside.

Reference： [1]Current Patent Assignee: SHANDONG UNIVERSITY - CN107236010, 2017, A Location in patent: Paragraph 0043; 0044; 0045-0047; 0055-0067; 0080-0084

77
[ 334-48-5 ]
[ 147-94-4 ]
[ 55726-41-5 ]

Yield	Reaction Conditions	Operation in experiment
64.3%	Stage #1: 1-decanoic acid With chloroformic acid ethyl ester; triethylamine In N,N-dimethyl-formamide for 0.333333h; Inert atmosphere; Cooling with ice; Stage #2: arabinosyl cytosine In N,N-dimethyl-formamide at 20℃; for 72h; Inert atmosphere;	1 Example 1 DA-Ara Prodrug Molecular Synthesis Analytical Balance Precision Weigh a certain amount of capric acid,Dissolved in anhydrous N,N-dimethylformamide (DMF) and placedIn a double-necked flask, triethylamine and ethyl chloroformate were added under stirring, and nitrogen was protected.The reaction was carried out for 20 min under ice bath conditions. Weigh a certain amount of cytarabine dissolved in 5mL of warm anhydrous DMF.Slowly drip the above reaction solution under stirring.The molar amount is citric acid: triethylamine: ethyl chloroformate: cytarabine=12:11:11:10,The reaction was returned to room temperature and the reaction was continued under nitrogen for 72 h.The progress of the reaction was monitored using a thin layer of plates. After the reaction was completed, anhydrous DMF was removed by vacuum distillation under reduced pressure.Dry overnight in vacuo to give the crude material.The crude product was dissolved in ethyl acetate, and the mixture was purified by silica gel column chromatography.Gradient elution with dichloromethane and methanol (150:1-70:1),The pure DA-Ara product was obtained as a white solid with a yield of 64.3%.

Reference： [1]Current Patent Assignee: SHANDONG UNIVERSITY - CN108409819, 2018, A Location in patent: Paragraph 0041

78
[ 154-42-7 ]
[ 147-94-4 ]
C₉H₁₃N₃O₅*C₅H₅N₅S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide; at 35.0℃; for 24.0h;	Add cytarabine (12.2 mg) and <strong>[154-42-7]thioguanin</strong>e (8.4 mg) to the vial.Add 5 ml of N,N'-dimethylformamide and stir at 35 C for 24 hours.Upon cooling to room temperature, an amphiphilic base conjugate is obtained.

Reference： [1]Patent: CN105535991,2018,B .Location in patent: Paragraph 0053; 0054

79
[ 544-63-8 ]
[ 147-94-4 ]
[ 55726-43-7 ]

Yield	Reaction Conditions	Operation in experiment
67.2%	Stage #1: n-tetradecanoic acid With chloroformic acid ethyl ester; triethylamine In N,N-dimethyl-formamide for 0.333333h; Cooling with ice; Inert atmosphere; Stage #2: arabinosyl cytosine In N,N-dimethyl-formamide at 20℃; for 72h; Inert atmosphere;	1 Example 1 MA-Ara Prodrug Molecular Synthesis Analyze the balance precision to weigh a certain amount of myristic acid,Soluble in anhydrous N,N-dimethylformamide (DMF)And placed in a double-necked flask, and added with triethylamine and ethyl chloroformate under stirring, nitrogen protection,The reaction was carried out for 20 min under ice bath conditions. Weigh a certain amount of cytarabine dissolved in 5mL of warm anhydrous DMF.The above reaction solution was slowly added dropwise under stirring, wherein the molar amount was myristic acid: triethylamine:Ethyl chloroformate: cytarabine = 12:11:11:10, the reaction returned to the roomThe reaction was continued under nitrogen protection for 72 h, and the progress of the reaction was monitored using a thin plate. After the reaction is over,The anhydrous DMF was evaporated under reduced pressure and dried in vacuo to give a crude material. The crude product was dissolved in ethyl acetate.A few column chromatography chromatography on silica gel, silica gel column chromatography, gradient elution with dichloromethane and methanol (150: 1-70:1),The pure MA-Ara product was obtained as a white solid with a yield of 67.2%.

Reference： [1]Current Patent Assignee: SHANDONG UNIVERSITY - CN108727449, 2018, A Location in patent: Paragraph 0042-0043

80
[ 124-04-9 ]
[ 147-94-4 ]
5-[1-((2R,3S,4S,5R)-3,4-Dihydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-2-oxo-1,2-dihydro-pyrimidin-4-ylcarbamoyl]-pentanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	Stage #1: Adipic acid With thionyl chloride; triethylamine In 1,4-dioxane at 110℃; for 4h; Inert atmosphere; Stage #2: arabinosyl cytosine With triethylamine In N,N-dimethyl-formamide at 20℃; Inert atmosphere;	6 Example 6 Preparation of cytarabine-succinic acid monoester prodrug (prodrug 6) 0.44 g (3 mmol) of adipic acid was dissolved in 15 ml of anhydrous dioxane, and 0.25 g (2.5 mmol) of triethylamine was added. Then, 0.28 g (2.4 mmol) of thionyl chloride was added dropwise, and the mixture was vacuumed under nitrogen, refluxed at 110 ° C for 4 h, and concentrated under reduced pressure. To a pale yellow oil, reconstituted with 10 ml of DMF. Add cytarabine 0.73g (3mmol), and add three at room temperature Ethylamine 0.19 g (1.8 mmol) was added to a vacuum of nitrogen and the reaction was stood overnight. Concentrate the reaction solution under reduced pressure A reddish brown oil was obtained. Column chromatography gave a white solid in 35% yield.

Reference： [1]Current Patent Assignee: SHENYANG PHARMACEUTICAL UNIVERSITY - CN108610384, 2018, A Location in patent: Paragraph 0065; 0066

81
[ 32315-10-9 ]
C₂₉H₅₈NO₉PS₂ [ No CAS ]
[ 147-94-4 ]
C₃₉H₆₉N₄O₁₅PS₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.25 g	Stage #1: bis(trichloromethyl) carbonate; C₂₉H₅₈NO₉PS₂ With dmap In dichloromethane at 20℃; for 2h; Inert atmosphere; Stage #2: arabinosyl cytosine In dichloromethane for 3h;	7 Synthesis of palmitic acid-sn-2-arabinosyl carbamate ethyldithiopropionate glycerophosphocholine (see Figure 6 for the route) 0.35 g palmitic acid-sn-2-hydroxyethyl dithiopropionic acid glycerol phosphate choline,0.10 g of triphosgene (BTC) was uniformly mixed in 100 mL of anhydrous dichloromethane. Under a nitrogen atmosphere, 0.15 g of a DMAP solution in dichloromethane was slowly added dropwise, and the reaction was stirred at room temperature for 2 h. To the above system, 0.15 g of Cytarabine was added and reacted for 3 hours. After that, the crude product was washed with aq. The product was purified by column chromatography to give 0.25 g of the product palmic acid-sn-2- cyanosyl carbamate ethyl dithiopropionate glycerol phosphate choline as a white solid.

Reference： [1]Current Patent Assignee: SOUTHEAST UNIVERSITY - CN110025789, 2019, A Location in patent: Paragraph 0116-0119

82
[ 108-24-7 ]
[ 147-94-4 ]
[ 6742-08-1 ]

Yield	Reaction Conditions	Operation in experiment
100%	With dmap; triethylamine In N,N-dimethyl-formamide at 20℃; for 8h;	4-N-acetyl-3',4',6'-O-triacetyl-cytarabine The cytarabine (300 mg) was dissolved in an acetic anhydride/DMF/TEA (1:1:1) mixture, and after the DMAP (5 mol%) is added. The reaction mixture was stirred at room temperature for 8 h (see reaction scheme). 4-N-acetyl-3’4’,6’-O-triacetyl-cytarabine. The product was isolated as yellow solid in quantitative yield. 1H NMR (300 MHz; CDCl3), d ppm (multiplicity; integration; J (Hz); position) 1.89 (s; 3H; H-2’’ acetyl linked to O-3’ arabinofuranosyl ring), 2.09-1.98 (m; 6H; H-2’’ acetyl linked to O-4’ and O-6’ arabinofuranosyl ring), 2.21 (s; 3H; H-2’’ acetyl linked to 4-N arabinofuranosyl ring), 4.16 (t; 1H; J = 10.5; H-5’ arabinofuranosyl ring), 4.33 (t; 2H; J = 12.3; H-6’ arabinofuranosyl ring), 5.04 (d; 1H; J = 12.2; H-4’ arabinofuranosyl ring), 5.49 (d; 1H; J = 2.5; H-3’ arabinofuranosyl ring), 6.29 (d; 1H; J = 3.4; H-2’ arabinofuranosyl ring), 7.43 (d; 1H; J = 7.6 Hz; H-5 cytosine ring), 7.88 (d; 1H; J = 7.6 Hz; H-6 cytosine ring). ESI-HRMS (positive mode) m/z: Calculated for C17H21N3O9: 411.3634; found, 434.1173 [M+Na]+. NMR carbon characterization and 2D correlation spectroscopy were reported previously.

Reference： [1]Berrio Escobar, Jhon Fernando; Marquez Fernandez, Diana Margarita; Giordani, Cristiano; Castelli, Francesco; Sarpietro, Maria Grazia [Journal of Thermal Analysis and Calorimetry, 2019, vol. 138, # 4, p. 2759 - 2767]

83
[ 147-94-4 ]
[ 107-92-6 ]
[ 34409-16-0 ]

Yield	Reaction Conditions	Operation in experiment
60%	Stage #1: butyric acid With triethylamine; diisopropyl-carbodiimide In N,N-dimethyl-formamide at 20℃; for 6h; Stage #2: arabinosyl cytosine With dmap In N,N-dimethyl-formamide at 20℃; for 8h;	Percylation reaction with butyric acid The DIC (1.5 equivalents with respect to theoretical amount of aliphatic acid) was dissolved in a butyric acid/ DMF/TEA (1:1:1) mixture; this was stirred at room temperature for 6 h for a pre-activation of the coupling agent, after the cytarabine (300 mg) and DMAP (5 mol%) were added. The reaction mixture was stirred at room temperature for 8 h (see reaction scheme in Fig. 1). 4-N-butyryl-3’,4’,6’-tributyryl-cytarabine. The product was isolated as yellow solid (60% yield). 1H NMR (600 MHz, DMSO-d6) d ppm (multiplicity; integration; J (Hz); position):1.3-1.0 (m; 20H; H-3’’ y H-4’’ butanoyl or butyryl chain), 1.8-1.6 (m; 8H; H-2’’ (a protons) butanoyl chain), 3,96 (m; 1H; H-6’ arabinofuranosyl ring), 4,05 (m; 1H; H-6’ arabinofuranosyl ring), 5.62 (m; 1H; H-5’ arabinofuranosyl ring), 5.67 (d; 1H; H-3’ arabinofuranosyl ring), 5,72 (d; 1H; H-4’ arabinofuranosyl ring), 6,05 (d; 1H; J = 4.5 Hz; H-2’ arabinofuranosyl ring), 7,61 (d; 1H; J = 8.1 Hz; H-5 cytosine ring), 7,78 (d; 1H; J = 8,2; H-6 cytosine ring). ESI-HRMS (positive mode) m/z: Calculated for C25H37N3O9: 523.5759; found, 546.4113 [M + Na]+.

Reference： [1]Berrio Escobar, Jhon Fernando; Marquez Fernandez, Diana Margarita; Giordani, Cristiano; Castelli, Francesco; Sarpietro, Maria Grazia [Journal of Thermal Analysis and Calorimetry, 2019, vol. 138, # 4, p. 2759 - 2767]

84
[ 544-63-8 ]
[ 147-94-4 ]
4-N-myristoyl-4',6'-O-dimyristoyl-cytarabine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30%	Stage #1: n-tetradecanoic acid With triethylamine; dicyclohexyl-carbodiimide In chloroform; N,N-dimethyl-formamide at 20℃; for 6h; Stage #2: arabinosyl cytosine With dmap In chloroform; N,N-dimethyl-formamide at 20℃; for 168h;	Per-acylation of amine and two hydroxyls groups General procedure: The esterification reaction for amine group (H2N-4) cytosine ring and hydroxyl groups (OH-4’ and OH-6’) of arabinofuranosyl ring of cytarabine with fatty was performed by Steglich esterification. DCC (1.5 equivalents with respect to fatty acid) was aggregated to fatty acid (4.5 equivalents with respect to nucleoside) solution in Chloroform/ DMF/TEA (1:2:1) mixture; this mix was stirred at room temperature for 6 h for a pre-activation, after DMAP (5 mol%) and cytarabine (300 mg) was added [13]. The reaction mixture was stirred at room temperature for 7 days (see reaction scheme). 4-N-myristoyl-4’,6’-O-dimyristoyl-cytarabine. The product was isolated as white solid (30% yield). 1H NMR (600 MHz; CDCl3), d ppm (multiplicity; integration; J (Hz); position): 0.92 (t; 9H; J = 6.6; H-14’’ myristoyl chain), 1.32 (m; 48H; H-4’’ to H-1300 myristoyl chain), 1.70 (m; 6H; H-3’’ (b protons) myristoyl chain), 2.40 (m; 6H; H-2’’ (a protons) myristoyl chain), 4.14 (m; 2H; H-6’ arabinofuranosyl ring), 4.44 (m; 1H; H-5’ arabinofuranosyl ring), 4.76 (d; 1H; J = 2.8; H-3’ arabinofuranosyl ring), 5.15 (m; 1H; H-4’ arabinofuranosyl ring), 6.08 (d; 1H; J = 3.2; H-2’ arabinofuranosyl ring), 7.45 (d; 1H; J = 7.8; H-5 cytosine ring), 7.90 (d; 1H; J = 7.8; 6 cytosine ring). ESI-HRMS (positive mode) m/z: Calculated for C51H91N3O8: 874.2835; found, 897.7647 [M+Na]+.

Reference： [1]Berrio Escobar, Jhon Fernando; Marquez Fernandez, Diana Margarita; Giordani, Cristiano; Castelli, Francesco; Sarpietro, Maria Grazia [Journal of Thermal Analysis and Calorimetry, 2019, vol. 138, # 4, p. 2759 - 2767]

85
[ 57-11-4 ]
[ 147-94-4 ]
4-N-stearoyl-4',6'-O-distearoyl-cytarabine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	Stage #1: stearic acid With triethylamine; dicyclohexyl-carbodiimide In chloroform; N,N-dimethyl-formamide at 20℃; for 6h; Stage #2: arabinosyl cytosine With dmap In chloroform; N,N-dimethyl-formamide at 20℃; for 168h;	Per-acylation of amine and two hydroxyls groups General procedure: The esterification reaction for amine group (H2N-4) cytosine ring and hydroxyl groups (OH-4’ and OH-6’) of arabinofuranosyl ring of cytarabine with fatty was performed by Steglich esterification. DCC (1.5 equivalents with respect to fatty acid) was aggregated to fatty acid (4.5 equivalents with respect to nucleoside) solution in Chloroform/ DMF/TEA (1:2:1) mixture; this mix was stirred at room temperature for 6 h for a pre-activation, after DMAP (5 mol%) and cytarabine (300 mg) was added [13]. The reaction mixture was stirred at room temperature for 7 days (see reaction scheme).

Reference： [1]Berrio Escobar, Jhon Fernando; Marquez Fernandez, Diana Margarita; Giordani, Cristiano; Castelli, Francesco; Sarpietro, Maria Grazia [Journal of Thermal Analysis and Calorimetry, 2019, vol. 138, # 4, p. 2759 - 2767]

86
allyl (S)-2-((allyloxycarbonyl)amino)-5-((4-((((4-nitrophenoxy) carbonyl)oxy)methyl)phenyl)amino)-5-oxopentanoate [ No CAS ]
[ 147-94-4 ]
(((4-((S)-5-allyl-4-(allyloxycarbonylamino)-5-oxopentanamido)benzyl)oxy)carbonyl)cytarabine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.016 g	With sodium hydroxide In tetrahydrofuran; water at 20℃; for 3h;	5.5-1 Synthesis Example 5-1 Synthesis of (((4-((S)-5-allyl-4-(allyloxycarbonylamino)-5-oxopentanamido)benzyl)oxy)carbonyl)cytarabine Allyl (S)-2-(allyloxycarbonylamino)-5-((4-((((4-nitrophenoxy)carbonyl)oxy)methyl)phenyl)amino)-5-oxopentanoate (0.030 g) was dissolved in tetrahydrofuran (1.85 mL), cytarabine (0.014 g) was added to the solution, and then a 1 N aqueous solution of sodium hydroxide (0.15 mL) was added thereto. The mixture was stirred for 3 hours at room temperature, subsequently ethyl acetate was added thereto, and an organic layer was obtained. The organic layer thus obtained was dried over anhydrous sodium sulfate, subsequently the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform/methanol=20/1 to 5/1). Thus, (((4-((S)-5-allyl-4-(allyloxycarbonylamino)-5-oxopentanamido)benzyl)oxy)carbonyl)cytarabine (0.016 g) was obtained. NMR [400 MHz, DMSO-d6, TMS] ppm: 1.79-1.93 (1H, m), 2.02-2.34 (1H, m), 3.49-3.63 (2H, m), 4.05-4.16 (1H, m), 4.47 (2H, d), 4.60 (2H, d), 4.92-5.09 (3H, m), 5.16-5.34 (4H, m), 5.68 (1H, d), 5.83 (1H, d), 5.84-5.97 (2H, m), 6.17 (1H, d), 7.24 (2H, d), 7.56 (2H, d), 7.63 (1H, d), 7.76 (1H, d), 10.00 (1H, brs).

Reference： [1]Current Patent Assignee: NIPPON KAYAKU CO LTD - US2020/190101, 2020, A1 Location in patent: Paragraph 0363; 0364-0366

87
[ 4965-84-8 ]
[ 147-94-4 ]
C₄₀H₅₇N₃O₁₀ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32%	Stage #1: 4-(((25R)-spirost-5-ene-3β-yl)oxy)-4-oxobutanoic acid With 1-hydroxy-pyrrolidine-2,5-dione; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 30h; Cooling with ice; Stage #2: arabinosyl cytosine In N,N-dimethyl-formamide at 20℃; for 48h; Inert atmosphere;
	Stage #1: 4-(((25R)-spirost-5-ene-3β-yl)oxy)-4-oxobutanoic acid With 1-hydroxy-pyrrolidine-2,5-dione; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 30h; Cooling with ice; Stage #2: arabinosyl cytosine In N,N-dimethyl-formamide at 20℃; for 48h; Inert atmosphere;	1.2; 2.2 Step 2. Synthesis of Diosgenin-Cytarabine (DG-Ara-C) Polymer Dissolve 100 mg of the diosgenin-succinate (DG-SA) obtained in the above steps in 5 mL of anhydrous dichloromethane, shake well, take 29.8 mg of N-hydroxysuccinimide (NHS) and add the above DG -SA solution system, shake well, take 70mg of N,N'-dicyclohexylcarbodiimide (DCC), add the above-obtained DG-SA and DCC dichloromethane solution system, mix well, ice bath for 6 hours , The reaction system was allowed to stand at room temperature for 24 hours to activate DG-SA.(2) The above reaction system is filtered to remove precipitation, the filtrate contains activated DG-SA, and the filtrate is concentrated and used for subsequent reactions.(3) Accurately weigh 130 mg of cytarabine and dissolve in 2 mL of N,N-dimethylformamide (DMF), shake well, add to the activated DG-SA solution system after preheating, and under the protection of nitrogen React at room temperature for 48 hours.(4) The resulting reaction system was removed solvent under vacuum conditions, and purified by flash chromatography, eluted with a 5% methanol-trichloromethane solution system to obtain diosgenin-cytarabine (DG- Ara-C) Polymer.

Reference： [1]Liao, Ai-Mei; Cai, Bangrong; Huang, Ji-Hong; Hui, Ming; Lee, Kyung-Ku; Lee, Kwang Youl; Chun, ChangJu [Food and Chemical Toxicology, 2021, vol. 148]
[2]Current Patent Assignee: HENAN UNIVERSTITY OF TECHNOLOGY - CN111298130, 2020, A Location in patent: Paragraph 0027; 0033-0037; 0043; 0049-0053

88
[ 24424-99-5 ]
[ 147-94-4 ]
C₁₄H₂₁N₃O₇ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide at 0 - 60℃;	9 Example 9, 2’,3’,5’-tri-O-tetradecanoyl cytarabine Cytarabine (VI,244mg, 1.0mmol) was dissolved in N,N-dimethylformamide solution (15ml), Boc2O (437mg, 2.0mmol) was added to the solution at 0, and after stirring for 10 minutes, Heat to 60°C and stir for 6-8 hours. Post-treatment: the reaction solution was washed with water and extracted with ethyl acetate (10ml). The extracts were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was separated and purified by column chromatography to obtain compound VII/. Compound VII/ was dissolved in dichloromethane solution (10ml), and then triethylamine (417μl, 3mmol) and myristyl chloride (VIII/, 890mg, 3.6mmol) were added to the reaction solution, after stirring for 3-6 hours at room temperature, The reaction is complete. Post-treatment: Concentrate the reaction solution, and use the residue (X/) directly in the next reaction.
	In N,N-dimethyl-formamide at 0 - 60℃;	1.9 Example 9, 2', 3', 5'-tri-O-tetradecanoyl cytarabine Cytarabine (VI, 244mg, 1.0mmol) was dissolved in N,N-dimethylformamide solution (15ml), and Boc2O (437mg, 2.0mmol) was added to the solution at0and stirred for 10 minutes Then, it was heated to 60°C and stirred for 6-8 hours.Post-treatment: the reaction solution was washed with water and extracted with ethyl acetate (10ml).The extracts were combined, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure.The residue was separated and purified by column chromatography to obtain compound VII/.Compound VII/ wasdissolved in dichloromethane solution (10ml), and triethylamine (417μl, 3mmol) and myristyl chloride (VIII/, 890mg,3.6mmol) were addedto the reaction solution in turn. After stirring at room temperature for 3-6 hours, The reaction is complete.Post-treatment: Concentrate the reaction solution, and use the residue (X/) directly in the next reaction.The above product / wasdissolved in dichloromethane solution (10ml), and trifluoroacetic acid (2ml) was added to remove the protective group to obtain a white solid compound II/as the title compound with an HPLC purity of >97.6%.

Reference： [1]Current Patent Assignee: CHINESE ACADEMY OF MEDICAL SCIENCES - CN113336816, 2021, A Location in patent: Paragraph 0086-0087
[2]Current Patent Assignee: CHINESE ACADEMY OF MEDICAL SCIENCES - CN113332305, 2021, A Location in patent: Paragraph 0092; 0118-0121

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	147-94-4	MDL No. :	MFCD00066487
Formula :	C₉H₁₃N₃O₅	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	UHDGCWIWMRVCDJ-CCXZUQQUSA-N
M.W :	243.22	Pubchem ID :	6253
Synonyms :	Cytosine β-D-arabinofuranoside;Cytosine Arabinoside;U-19920A;NSC 287459;NSC 63878;1-β-D-Arabinofuranosylcytosine;Ara-C	Chemical Name :	4-Amino-1-((2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one

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