4740-78-7|1,3-Dioxan-5-ol| Ambeed

Num. heavy atoms	7
Num. arom. heavy atoms	0
Fraction Csp3	1.0
Num. rotatable bonds	0
Num. H-bond acceptors	3.0
Num. H-bond donors	1.0
Molar Refractivity	22.56
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	38.69 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.33
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	-0.82
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	-0.65
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	-1.05
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	0.57
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	-0.12

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	0.03
Solubility	112.0 mg/ml ; 1.07 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Highly soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	0.49
Solubility	320.0 mg/ml ; 3.07 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Highly soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	0.41
Solubility	266.0 mg/ml ; 2.56 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	No
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-7.52 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	2.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	2.26

Application In Synthesis of [ 4740-78-7 ]

* 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.

Downstream synthetic route of [ 4740-78-7 ]

[ 4740-78-7 ] Synthesis Path-Downstream 1~50

1
[ 4740-78-7 ]
[ 98-88-4 ]
[ 49784-60-3 ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1929,vol. 48,p. 187.
[2]Journal of the American Chemical Society,1928,vol. 50,p. 3122.

2
[ 4740-78-7 ]
[ 103-71-9 ]
[ 92368-06-4 ]

References: [1]Recueil des Travaux Chimiques des Pays-Bas,1929,vol. 48,p. 187.

3
[ 4740-78-7 ]
[ 77-78-1 ]
[ 99586-36-4 ]

References: [1]Journal of the American Chemical Society,1928,vol. 50,p. 3122.

4
[ 4740-78-7 ]
[ 51953-54-9 ]

References: [1]Annales Pharmaceutiques Francaises,1950,vol. 8,p. 273,285.

5
[ 49784-60-3 ]
[ 4740-78-7 ]

References: [1]Journal of Organic Chemistry,2007,vol. 72,p. 4156 - 4162.
[2]Annales Pharmaceutiques Francaises,1950,vol. 8,p. 273,285.
[3]Tetrahedron,1959,vol. 7,p. 10,13.

6
[ 50-00-0 ]
[ 56-81-5 ]
[ 5464-28-8 ]
[ 4740-78-7 ]

Yield	Reaction Conditions	Operation in experiment
95.6%	With dihydrogen peroxide; nitric acid; cetyltrimethylammonim bromide; ferric nitrate; In water; at 80℃; for 5.0h;	Will be 920g of glycerin,990gParaformaldehyde and20 g of the supported solid super acid catalyst prepared in Example 2 was addedIn the reaction device, the reaction is heated to 80 C, and the water having a lower boiling point and the trioxane formed in the reaction process enters the fractionation device.According to the principle that the boiling point of paraformaldehyde is lower than water, the triacetal is fractionated back to the reaction unit through a fractionation device.The reaction was carried out as a raw material, and the reaction was completed for 5 hours to obtain glycerol formal, and the product was analyzed by HPLC-MS.At 96.3%, the ratio of the six-membered ring product to the product of the five-membered ring in the product was 70:25.
	With Dowex 50; In toluene; at 100℃;Dean-Stark; Reflux;	A 250 mL three neck flask equipped with a stirrer, an addition funnel, and a Dean-Stark trap was charged with glycerol (9.2 g, 0.1 mol), paraformaldehyde (2.7 g, 0.09 mol), activated ion exchange resin Dowex 50 (10 wt.%), and anhydrous toluene (70 mL). The reaction mixture was refluxed until calculated amount of water was distilled off. The mixture was cooled and filtered. The solvent was removed in low vacuum. Distillation of the residue afforded a mixture of compounds 1a and 1b in the yield of 9.2 g (93%), b.p. 190-195 C (760 Torr). An isomeric ratio was determined by 1H NMR spectroscopy from the integrated intensity ratio of the signals of H(4) methyne protons (deltaH 3.5-4.0) of dioxolane 1a and H(5) methyne proton (deltaH 3.5-4.0) of dioxane 1b. Compound 1a. MS (EI, 70 eV), m/z (Irel (%)): 103 [M - H]+ (not detected), 73 (75), 57 (15), 45 (100), 31 (15). Compound 1b. MS (EI, 70 eV), m/z (Irel (%)): 103 [M - H]+ (not detected), 87 (1), 74 (31), 45 (17), 44 (100), 31 (12).
	With 1,3,5-Trioxan; at 80℃; for 5.0h;	920 g of glycerin, 990 g of trioxane and 20 g of the supported solid superacid catalyst prepared in Example 2 were charged into a reaction apparatus, and heated to 80 C to react, and the lower boiling water and trioxane formed during the reaction were fractionated. The device, according to the principle that the boiling point of the paraformaldehyde is lower than water, the triacetal is fractionated back to the reaction device through the fractionation device to continue the reaction as a raw material, and the reaction is finished for 5 hours, thereby obtaining glycerol formal, which is analyzed by HPLC-MS. The yield of the product was 93.5%, and the ratio of the product of the six-membered ring product to the product of the five-membered ring was 77:23.

References: [1]Patent: CN109535122,2019,A .Location in patent: Paragraph 0029-0034.
[2]Tetrahedron Letters,1987,vol. 28,p. 6601 - 6604.
[3]Bulletin de la Societe Chimique de France,1991,p. 566 - 573.
[4]Journal of applied chemistry of the USSR,1991,vol. 64,p. 1448 - 1451.
    Zhurnal Prikladnoi Khimii (Sankt-Peterburg, Russian Federation),1991,vol. 64,p. 1591 - 1595.
[5]Recueil des Travaux Chimiques des Pays-Bas,1929,vol. 48,p. 187.
[6]Recueil des Travaux Chimiques des Pays-Bas,1929,vol. 48,p. 187.
[7]Journal of Catalysis,2007,vol. 245,p. 428 - 435.
[8]Journal of Organic Chemistry,2007,vol. 72,p. 4156 - 4162.
[9]Green Chemistry,2009,vol. 11,p. 38 - 41.
[10]Journal of Catalysis,2010,vol. 271,p. 351 - 357.
[11]ChemCatChem,2013,vol. 5,p. 2893 - 2904.
[12]Catalysis science and technology,2014,vol. 4,p. 2287 - 2292.
[13]Green Chemistry,2014,vol. 16,p. 4985 - 4993.
[14]Catalysis science and technology,2014,vol. 4,p. 4242 - 4249.
[15]Russian Journal of General Chemistry,2014,vol. 84,p. 1930 - 1933.
    Zh. Obshch. Khim.,2014,vol. 84,p. 1652 - 1655,4.
[16]Applied Catalysis A: General,2016,vol. 509,p. 143 - 152.
[17]Russian Chemical Bulletin,2015,vol. 64,p. 2095 - 2099.
    Izv. Akad. Nauk, Ser. Khim.,2015,p. 2095 - 2099,5.
[18]ChemSusChem,2014,vol. 7,p. 2728 - 2734.
[19]ChemCatChem,2018,vol. 10,p. 1918 - 1925.
[20]Patent: CN109734695,2019,A .Location in patent: Paragraph 0029-0032.
[21]Journal of the Chinese Chemical Society,2020.

7
[ 50-00-0 ]
[ 56-81-5 ]
[ 4740-78-7 ]

Yield	Reaction Conditions	Operation in experiment
	With Amberlyst-15; at 100℃; for 1.0h;	To the reaction vessel was added 40g octadecene, heated with stirring, under vigorous stirring,3g of glycerin was added dropwise octadecene, the two were stirred evenly, 0.3g of catalyst was added Amberlyst-15, was added dropwise 0.9g of formaldehyde, heated to 100 , the reaction 1h, after chromatography, the conversion of formaldehyde was 95% of the resulting product, the cyclic acetal 1,3-glyceraldehyde (5-hydroxy-1,3-dioxane) has a selectivity of 80%.

References: [1]Canadian Journal of Chemistry,1983,vol. 61,p. 1924 - 1932.
[2]Chemische Berichte,1894,vol. 27,p. 1894.
    Justus Liebigs Annalen der Chemie,1896,vol. 289,p. 29.
[3]Justus Liebigs Annalen der Chemie,1904,vol. 335,p. 323.
    Justus Liebigs Annalen der Chemie,1907,vol. 357,p. 215,300.
[4]Chemische Berichte,1894,vol. 27,p. 1894.
    Justus Liebigs Annalen der Chemie,1896,vol. 289,p. 29.
[5]Patent: CN106632229,2017,A .Location in patent: Paragraph 0020; 0021; 0022; 0023; 0024; 0025; 0026-0029.

8
[ 4740-78-7 ]
[ 75-44-5 ]
C₅H₇ClO₄ [ No CAS ]

References: [1]Patent: FR2237621,1975, .
Patent: DE2422718,1975, .
Chem.Abstr.,1975,vol. 83.

9
[ 4740-78-7 ]
[ 87683-81-6 ]

References: [1]Canadian Journal of Chemistry,1983,vol. 61,p. 1924 - 1932.
[2]Organic Letters,2005,vol. 7,p. 1383 - 1385.

10
[ 50-00-0 ]
[ 124-63-0 ]
[ 56-81-5 ]
[ 4740-78-7 ]
1,3-dioxolan-4-ylmethyl methanesulfonate [ No CAS ]

References: [1]Tetrahedron Letters,1993,vol. 34,p. 4335 - 4336.

11
[ 50-00-0 ]
[ 98-59-9 ]
[ 56-81-5 ]
[ 4740-78-7 ]
[ 85608-69-1 ]

References: [1]Tetrahedron Letters,1993,vol. 34,p. 4335 - 4336.

12
[ 109-87-5 ]
[ 56-81-5 ]
[ 5464-28-8 ]
[ 4740-78-7 ]

References: [1]Tetrahedron Letters,1987,vol. 28,p. 6601 - 6604.
[2]Bulletin de la Societe Chimique de France,1991,p. 566 - 573.
[3]Bulletin de la Societe Chimique de France,1991,p. 566 - 573.

13
[ 4740-78-7 ]
[ 159383-03-6 ]
9-[2-Bromo-1-([1,3]dioxan-5-yloxy)-1-methyl-ethyl]-9H-purin-6-ylamine [ No CAS ]

References: [1]Chemistry Letters,1995,p. 243.

14
[ 4740-78-7 ]
E-6-amino-9-<1-methyl-2-(tetrahydropyran-2-yloxy)ethenyl>-9H-purine [ No CAS ]
9-[2-Bromo-1-([1,3]dioxan-5-yloxy)-1-methyl-2-(tetrahydro-pyran-2-yloxy)-ethyl]-9H-purin-6-ylamine [ No CAS ]

References: [1]Chemistry Letters,1995,p. 243.

15
[ 5464-28-8 ]
[ 4740-78-7 ]
[ 6362-89-6 ]
[ 219133-84-3 ]
[ 219133-79-6 ]

References: [1]Russian Journal of General Chemistry,1998,vol. 68,p. 881 - 886.

16
[ 4740-78-7 ]
[ 112-80-1 ]
[ 277749-20-9 ]