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[ CAS No. 146-78-1 ] {[proInfo.proName]}

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Chemical Structure| 146-78-1
Chemical Structure| 146-78-1
Structure of 146-78-1 * Storage: {[proInfo.prStorage]}
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Product Details of [ 146-78-1 ]

CAS No. :146-78-1 MDL No. :MFCD00866394
Formula : C10H12FN5O4 Boiling Point : -
Linear Structure Formula :- InChI Key :HBUBKKRHXORPQB-UUOKFMHZSA-N
M.W : 285.23 Pubchem ID :8975
Synonyms :
2FA

Calculated chemistry of [ 146-78-1 ]

Physicochemical Properties

Num. heavy atoms : 20
Num. arom. heavy atoms : 9
Fraction Csp3 : 0.5
Num. rotatable bonds : 2
Num. H-bond acceptors : 8.0
Num. H-bond donors : 4.0
Molar Refractivity : 62.63
TPSA : 139.54 Ų

Pharmacokinetics

GI absorption : Low
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -8.61 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.95
Log Po/w (XLOGP3) : -0.8
Log Po/w (WLOGP) : -1.74
Log Po/w (MLOGP) : -2.31
Log Po/w (SILICOS-IT) : -1.94
Consensus Log Po/w : -1.17

Druglikeness

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

Water Solubility

Log S (ESOL) : -1.31
Solubility : 14.1 mg/ml ; 0.0495 mol/l
Class : Very soluble
Log S (Ali) : -1.65
Solubility : 6.37 mg/ml ; 0.0223 mol/l
Class : Very soluble
Log S (SILICOS-IT) : 0.14
Solubility : 389.0 mg/ml ; 1.36 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 4.0

Safety of [ 146-78-1 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 146-78-1 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 146-78-1 ]
  • Downstream synthetic route of [ 146-78-1 ]

[ 146-78-1 ] Synthesis Path-Upstream   1~12

  • 1
  • [ 2096-10-8 ]
  • [ 146-78-1 ]
  • [ 1818-71-9 ]
Reference: [1] Nucleosides and Nucleotides, 1994, vol. 13, # 1-3, p. 673 - 678
  • 2
  • [ 146-78-1 ]
  • [ 700-49-2 ]
  • [ 72075-46-8 ]
Reference: [1] Nucleosides and Nucleotides, 1999, vol. 18, # 4-5, p. 745 - 757
  • 3
  • [ 146-78-1 ]
  • [ 700-49-2 ]
  • [ 18646-11-2 ]
Reference: [1] Nucleosides and Nucleotides, 1999, vol. 18, # 4-5, p. 745 - 757
  • 4
  • [ 161109-77-9 ]
  • [ 146-78-1 ]
YieldReaction ConditionsOperation in experiment
82% With ethanol; potassium carbonate In water at 35 - 45℃; for 20 - 48 h; Example 1Manufacture of 2-fluoro-ara-adenineMW =41 1 .35g/mol MF =C16H18FN5O7 MW =285.24g/mol MF =C10H12FN5O4 180 to 220 kg of ethanol are provided in an agitator container and 8 to 12 kg of purified water are added. 15 kg of 2-fluoro-ara-adenine triacetate and 2.25 to 2.75 kg potassium carbonate are added. This mixture is heated to 35 to 45 0C and stirred for 20 to 48 h. The reaction mixture is cooled down to 0 to 20 0C and 190 to 230 kg of purified water are added. Subsequently, the pH value is adjusted to a value of 5 to 7 using an organic or mineral acid, preferably acetic acid. Activated carbon is added to the reaction mixture and the reaction mixture is brought to reflux. The activated carbon is filtered off while warm and the filtrate is inoculated with 2-fluoro-ara-adenine within a temperature range of 40 to 75 0C. The inoculated amount lies within a range of 0 to 1 kg. The resulting suspension is cooled down to -12 to 10 0C and stirred for at least an additional 60 min. The isolated solid cake is washed with a mixture of ethanol and purified water and dried under vacuum at a preferred shell temperature of 80 to 100 0C using a carrier gas.The yield lies at 82percent of the theory.
Reference: [1] Patent: WO2010/130778, 2010, A1, . Location in patent: Page/Page column 9
  • 5
  • [ 24649-69-2 ]
  • [ 146-78-1 ]
Reference: [1] Organic Process Research and Development, 2012, vol. 16, # 5, p. 840 - 842
  • 6
  • [ 3083-77-0 ]
  • [ 700-49-2 ]
  • [ 146-78-1 ]
Reference: [1] Process Biochemistry, 2012, vol. 47, # 12, p. 2182 - 2188
[2] Russian Journal of Bioorganic Chemistry, 2009, vol. 35, # 6, p. 739 - 745
  • 7
  • [ 52522-49-3 ]
  • [ 4060-34-8 ]
  • [ 143482-58-0 ]
  • [ 146-78-1 ]
Reference: [1] Patent: US5180824, 1993, A,
  • 8
  • [ 75607-67-9 ]
  • [ 146-78-1 ]
Reference: [1] Molecular Pharmacology, 1995, vol. 47, # 5, p. 1072 - 1079
[2] Nucleosides, Nucleotides and Nucleic Acids, 2006, vol. 25, # 3, p. 289 - 297
  • 9
  • [ 146-78-1 ]
  • [ 75607-67-9 ]
YieldReaction ConditionsOperation in experiment
40%
Stage #1: With triethyl phosphate; trichlorophosphate In toluene at -20 - -10℃; for 51.5 - 52.5 h;
EXAMPLE 1; Fludarabine (19. 5g ; 0.0683 moles) and (EtO) 3PO (79.1 ml; 0.465 moles) are introduced into a reactor cooled to-15/-20°C. POC13 (15.3 ml; 0.164 moles) is added dropwise over a period of approximately 1 hour while maintaining the internal temperature at - 10/-15°C. Agitation is maintained at-10/-15°C for 48 hours; the reaction is regarded as complete when the amount of fludarabine, in the HPLC area, is less than 2percent. Cold toluene (780 ml; 40 volumes) is then added over a period of approximately 1.5 hours and agitation is maintained, still at - 10/-15°C, for 1-2 hours. Filtration is carried out and the filter cake is washed with toluene (20 ml). The moist solid (approximately 35 g) is suspended in H20 (40 ml) and the pH is adjusted to 11 with 32percent NaOH (approximately 20 ml). The solution is percolated into a beaker containing Dowex resin [the resin must first be activated and washed as follows: washing is effected with demineralized water until the washing liquors are colourless; acidification with 5percent HCl (approximately 200 ml) is carried out and washing is effected to a neutral pH with demineralized water]. The whole is agitated for approximately 15 minutes and filtered over a septum. The resin is resuspended in H20 (500 ml). Agitation is carried out for 15 minutes followed by filtering over a septum. This operation is repeated until no more fludarabine phosphate is present in the filtrate. The fractions containing product are reduced in volume by evaporation under vacuum (at a maximum temperature of 30-35°C) until the desired product starts to precipitate, this product finally being filtered and dried under vacuum at 60°C to constant weight. 10. lg (40percent yield) of a white solid having a purity greater than 97.5percent are obtained. It is possible to recrystallize this solid as follows: it is suspended in 10 volumes of water and the whole is heated at 70°C for 1 hour; the whole is filtered hot, washing the filter cake with acetone. A white solid having a purity greater than 99percent is obtained.
Reference: [1] Patent: WO2005/40183, 2005, A2, . Location in patent: Page/Page column 4-5
[2] Advanced Synthesis and Catalysis, 2014, vol. 356, # 2-3, p. 563 - 570
  • 10
  • [ 146-78-1 ]
  • [ 78-40-0 ]
  • [ 75607-67-9 ]
YieldReaction ConditionsOperation in experiment
96.5% at -5 - -1℃; for 15 h; Fludarabine (10g), triethyl phosphate (90mL), phosphorus oxychloride (6mL) were placed under stirring -5~-10°C low temperature circulating pump, while maintaining the internal temperature -5 ~ -1 ° C; stirring reaction at -5 ~ -1 ° C for 15 hours; when the amount of fludarabine in the HPLC detection area, less than 2percent is considered The reaction was completed, then pure water (50 mL) was added to the obtained mixture under stirring, and washed with dichloromethane. The obtained aqueous phase was adjusted to pH=3 with 50percent NaOH solution, concentrated under reduced pressure at 35-40 ° C, and recrystallized. Filtration, the filter cake was washed with a small amount of ethanol and water to obtain a white solid. The white solid was dried under vacuum at 45-50 ° C for 10-12 hours to obtain a crude product of fludarabine phosphate having a purity of 99.2percent and a yield of 73.3percent.The crude fludarabine phosphate obtained by the above preparation method is added to 100 mL of pure water at room temperature, stirred uniformly, and 50percent NaOH solution is slowly added dropwise until completely dissolved, and the filtrate is added dropwise to a dilute hydrochloric acid solution at room temperature with a white solid. Precipitate,After suction filtration, the filter cake was washed with a small amount of ethanol and water to obtain a white solid. The white solid was vacuum-dried at 45-50 ° C for 10-12 hours to obtain fludarabine phosphate. The purity was 99.9percent, and the yield was 96.5. percent.
81.02%
Stage #1: at -6℃; for 0.333333 h;
Stage #2: for 12 h;
To a 500 mL flask was added 20 g of fludarabine followed by 200 mL of triethyl phosphate, and the flask was placed at a low temperature of -6 ° CReaction bath, 20min after slowly dropping phosphorus oxychloride 20mL (side drop while stirring), the reaction 12 hours (TCL tracking). Reaction reachedTo the request after the flask quickly add 80mL water and 200mL dichloroethane, standing for 30 minutes after the extraction of water and organic phase, the waterAdjust the pH value to 2-3. Recrystallization white floc with a Buchner funnel filter, vacuum dry weighing a white powder20.71 g, yield 81.02percent, HPLC mass fraction 99.95percent,
Reference: [1] Patent: CN104592337, 2018, B, . Location in patent: Paragraph 0033; 0034; 0035; 0036; 0037; 0039; 0040; 0042
[2] Patent: CN105859812, 2016, A, . Location in patent: Paragraph 0009
  • 11
  • [ 512-56-1 ]
  • [ 146-78-1 ]
  • [ 75607-67-9 ]
Reference: [1] Patent: US5296589, 1994, A,
[2] Patent: US5110919, 1992, A,
  • 12
  • [ 146-78-1 ]
  • [ 78-40-0 ]
  • [ 7440-44-0 ]
  • [ 75607-67-9 ]
Reference: [1] Patent: US4357324, 1982, A,
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