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[ CAS No. 33494-80-3 ] {[proInfo.proName]}

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Cat. No.: {[proInfo.prAm]}
Chemical Structure| 33494-80-3
Chemical Structure| 33494-80-3
Structure of 33494-80-3 * Storage: {[proInfo.prStorage]}
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Quality Control of [ 33494-80-3 ]

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Product Details of [ 33494-80-3 ]

CAS No. :33494-80-3 MDL No. :MFCD03840344
Formula : C8H18KO4P Boiling Point : -
Linear Structure Formula :- InChI Key :ZSWXMOQFFWMZQH-UHFFFAOYSA-M
M.W : 248.30 Pubchem ID :23674467
Synonyms :

Calculated chemistry of [ 33494-80-3 ]

Physicochemical Properties

Num. heavy atoms : 14
Num. arom. heavy atoms : 0
Fraction Csp3 : 1.0
Num. rotatable bonds : 4
Num. H-bond acceptors : 4.0
Num. H-bond donors : 0.0
Molar Refractivity : 51.11
TPSA : 68.4 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -7.14 cm/s

Lipophilicity

Log Po/w (iLOGP) : -2.64
Log Po/w (XLOGP3) : 0.95
Log Po/w (WLOGP) : 3.16
Log Po/w (MLOGP) : 1.04
Log Po/w (SILICOS-IT) : 0.76
Consensus Log Po/w : 0.65

Druglikeness

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

Water Solubility

Log S (ESOL) : -1.71
Solubility : 4.8 mg/ml ; 0.0193 mol/l
Class : Very soluble
Log S (Ali) : -1.97
Solubility : 2.64 mg/ml ; 0.0106 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -1.23
Solubility : 14.6 mg/ml ; 0.0587 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 3.99

Safety of [ 33494-80-3 ]

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

Application In Synthesis of [ 33494-80-3 ]

* 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 [ 33494-80-3 ]
  • Downstream synthetic route of [ 33494-80-3 ]

[ 33494-80-3 ] Synthesis Path-Upstream   1~5

  • 1
  • [ 33494-80-3 ]
  • [ 33494-81-4 ]
YieldReaction ConditionsOperation in experiment
98% With hydrogenchloride In water at 0℃; Concentrated HC1 (2.89 mL, 34.6 mmol) was added slowly to a solution ofpotassium di-tert-butyl phosphate (8.6 g, 34.6 mmol) in water (10 mL) at 0°C. Theprecipitated solid was collected by filtration, washed with a small amount of ice-water (5 mL), and dried in vacuo to provide Intermediate 7A (7.1 g, 33.8 mmol, 98 percent yield) as awhite solid.
4 g With hydrogenchloride In water [095] In one embodiment, the present invention pmvides a method of preparing a reagent for use in preparing a prodrug of 6-cyclohexyl-1-hydroxy-4-methylpyridin-2(1H)-one, which method can include reaction Scheme 2 as shown in Figure 2. The reaction Scheme 2 provides a reagent for preparation of a reagent of the POM prodrug moiety, which is ditert-butyl(choloromethyl)phosphate. Briefly, potassium di-tert phosphate (5 g, 20 mmol)is dissolved in a minimum amount of cold water and 6 N HC1 is added drop-wise in order to form a precipitate, and then the precipitate is washed with cold water, which is then filtered and dried under vacuum in order to form di-tert phosphate. The di-tert-phosphate (4 g, 19 mmol) is then dissolved in about 100 mL acetone with tetramethylammonium hydmxide added drop-wise until reaching about pH 7, and then the solvent is removed anddried under vacuum to pmduce tetra-methyl ammonium di-tert-butyl phosphate. Tetramethyl ammonium di-tert-butyl phosphate (5.11 g, 18 mmol) is then reacted with iodocholoro methane (CH2CII) (25 g, 142 mmol, 7.88 equivalent) in about 150 ML DME and refluxed for about 2 hours before being filtered to remove the precipitate, removal of the solvent, and then dissolved in EA/H, and then filtered through a silica bed, and thesolvent is removed and the product is dried to obtain di-tertbutyl(choloromethyl)phosphate. A TLC is shown to confirm product.
Reference: [1] Patent: WO2018/17910, 2018, A1, . Location in patent: Page/Page column 43; 44
[2] Patent: EP1051181, 2004, B1, . Location in patent: Page/Page column 15
[3] Patent: US2012/35134, 2012, A1, . Location in patent: Page/Page column 52
[4] Patent: US8426450, 2013, B1, . Location in patent: Page/Page column 33
[5] Patent: US2013/252938, 2013, A1, . Location in patent: Paragraph 0652
[6] Patent: US2015/111858, 2015, A1, . Location in patent: Paragraph 0063
[7] Patent: WO2016/77346, 2016, A1, . Location in patent: Paragraph 095
[8] Patent: US9403772, 2016, B2, . Location in patent: Page/Page column 37
  • 2
  • [ 13086-84-5 ]
  • [ 33494-80-3 ]
YieldReaction ConditionsOperation in experiment
5 g
Stage #1: With potassium permanganate; potassium hydrogencarbonate In water at 20℃; for 1.5 h; Cooling with ice
Stage #2: With pyrographite In water at 60℃; for 0.25 h;
Di-tert-butyl phosphohite (40.36 mmole) was combined with potassium bicarbonate (24.22 mmole) in 35 ml of water. The solution was stirred in an ice bath and potassium permanganate (28.25 mmole) was added in three equal portions over one hour's time. The reaction as then allowed to continue at room temperature for an additional half hour. Decolorizing carbon (600 mg) was then incorporated as the reaction was heated to 60° C. for 15 minutes. The reaction was then vacuum filtered to remove solid magnesium dioxide. The solid was washed several times with water. The filtrate was then combined with one gram of decolorizing carbon and heated at 60° C. for an additional twenty minutes. The solution was again filtered to yield a colorless solution, which was then evaporated under vacuum to afford crude Di-tert-butyl phosphate potassium salt. Di-tert-butyl phosphate potassium salt (5 g, 20.14 mmole) was dissolved in methanol (15 g): to this solution at 0° C. a slight excess of concentrated HCl is slowly added with efficient stirring at 0° C. The addition of acid causes the precipitation of potassium chloride. The solid is then filtered and washed with methanol. The compound in the mother liquor is then converted to the ammonium form by adding an equal molar amount of tetramethylammonium hydroxide (3.65 g, 20.14 mmole) while keeping the reaction cooled by a salt/ice bath with efficient stirring. The resulting clear solution is placed under reduced pressure to give the crude product. To the tetramethylammonium di-tert-butyl-phosphate dissolved in refluxing dimethoxyethane is then added 4.3 grams of chloroiodomethane (24.16 mmole) and stirred for 1-2 hours. The reaction is then filtered and the filtrate is placed under reduced pressure to concentrate the solution in DME. The chloromethyl di-tert-butyl phosphate 12-16percent in DME is used in the synthesis of 4-(5-(2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethylpropanamido)-4-(o-tolyl)pyridin-2-yl)-1-methyl-1-((phosphonooxy)methyl)piperazin-1-ium without further purifications (60percent yield): 1HNMR (CD3OD, 300 MHz) δ 1.51 (s, 12H), 5.63 (d, 2H, J=14.8). 31P-NMR (CD3OD, 300 MHz) δ −11.3 (s, 1P)
Reference: [1] Patent: EP1051181, 2004, B1, . Location in patent: Page/Page column 15
[2] Patent: US8426450, 2013, B1, . Location in patent: Page/Page column 32; 33
[3] Patent: US9403772, 2016, B2, . Location in patent: Page/Page column 37
[4] Patent: JP2015/17121, 2015, A, . Location in patent: Paragraph 0179-0181
  • 3
  • [ 13086-84-5 ]
  • [ 33494-80-3 ]
Reference: [1] Organic Process Research and Development, 2014, vol. 18, # 5, p. 636 - 642
[2] Tetrahedron, 1971, vol. 27, p. 3163 - 3170
[3] Patent: WO2010/122089, 2010, A1, . Location in patent: Page/Page column 77-78
  • 4
  • [ 33494-80-3 ]
  • [ 68695-48-7 ]
Reference: [1] Patent: US9403772, 2016, B2,
  • 5
  • [ 2472-88-0 ]
  • [ 33494-80-3 ]
  • [ 68695-48-7 ]
Reference: [1] Synthesis, 1978, p. 770 - 771
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