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Structure of 955369-56-9

Chemical Structure| 955369-56-9

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Product Details of [ 955369-56-9 ]

CAS No. :955369-56-9
Formula : C17H19N5O2S
M.W : 357.43
SMILES Code : CSC1=NC2=C(C=N1)C(=O)N(CC=C)N2C1=NC(=CC=C1)C(C)(C)O
MDL No. :MFCD19443207
InChI Key :CTAHQYLRFXBFKB-UHFFFAOYSA-N
Pubchem ID :67170189

Safety of [ 955369-56-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 955369-56-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 25
Num. arom. heavy atoms 15
Fraction Csp3 0.29
Num. rotatable bonds 5
Num. H-bond acceptors 5.0
Num. H-bond donors 1.0
Molar Refractivity 98.67
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

111.13 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

3.02
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

2.14
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

2.0
Log Po/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.

1.8
Log Po/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

2.05
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.2

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-3.52
Solubility 0.108 mg/ml ; 0.000303 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-4.11
Solubility 0.028 mg/ml ; 0.0000784 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately 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

-4.12
Solubility 0.0271 mg/ml ; 0.0000759 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately 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

Yes
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.

-6.96 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

0.0
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

1.0 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)

3.34

Application In Synthesis of [ 955369-56-9 ]

* 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 [ 955369-56-9 ]

[ 955369-56-9 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 638218-78-7 ]
  • [ 955368-90-8 ]
  • [ 955369-56-9 ]
YieldReaction ConditionsOperation in experiment
74% With copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 80℃; Step-3: Synthesis of 2-allyl-1-[6-(1-hydroxy-1-methyl-ethyl)-2-pyridyl]-6-methylsulfanyl-pyrazolo[3,4-d]pyrimidin-3-one To a stirred solution of 2-allyl-6-methylsulfanyl-1H-pyrazolo[3,4-d]pyrimidin-3-one (200 mg, 0.90 mmol, 1.0 eq) and <strong>[638218-78-7]2-(6-bromo-2-pyridyl)propan-2-ol</strong> (233 mg, 1.08 mmol, 1.20 eq) in 10 mL of dioxane were added copper iodide (171 mg, 0.90 mmol, 1.0 eq), potassium carbonate (186 mg, 1.35 mmol, 1.5 eq) and N,N'-dimethylethylenediamine (87 mg, 0.99 mmol, 1.1 eq) and stirred at 80 C. for overnight. After completion of reaction, solvent was removed under reduced pressure; residue was diluted with water and extracted with ethyl acetate (30 mL*3). Combined organic layer was washed with brine solution, dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford crude product, which was purified by flash chromatography to afford 240 mg (74%) of 2-allyl-1-[6-(1-hydroxy-1-methyl-ethyl)-2-pyridyl]-6-methylsulfanyl-pyrazolo[3,4-d]pyrimidin-3-one.
47% With copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 95℃; Into a lOOO-mL 3-necked round-bottom flask, was placed 6-(methylsulfanyl)-2-(prop-2-en-l-yl)-lH,2H,3H- pyrazolo[3,4-d]pyrimidin-3-one (20 g, 89.98 mmol, 1.00 equiv), <strong>[638218-78-7]2-(6-bromopyridin-2- yl)propan-2-ol</strong> (24 g, 111.07 mmol, 1.23 equiv), 1,4-dioxane (500 mL), iodocopper (17.1 g, 89.79 mmol, 1.0 equiv), K2C03 (17.1 g, 122.83 mmol, 1.37 equiv). This was followed by the addition of methyl [2-(methylamino) ethyl] amine (10.8 mL) dropwise with stirring. The resulting solution was stirred overnight at 95C in an oil bath. The resulting mixture was cooled to room temperature. The mixture was then quenched by the addition of 100 mL of water. The resulting mixture was concentrated under vacuum. The residue was extracted with 3x500 mL of ethyl acetate and the organic layers combined. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:5- 1:3). This resulted in 15 g (47%) of l-[6-(2-hydroxypropan-2-yl) pyridin-2-yl]-6-(methylsulfanyl)-2-(prop-2-en-l-yl)-lH,2H,3H- pyrazolo[3,4-d]pyrimidin-3-one as a white solid. LC-MS(ES, m/z) M+l=358
With copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 95℃; General procedure: 2.4 mL of N,N?-dimethylethylenediamine was added to 1,4-dioxane (50 mL) solution of 4.44 g of 2-allyl-6-(methylthio)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one, 3.80 g of copper(I) iodide, 5.33 g of 2-iodopyridine and 3.80 g of potassium carbonate, and stirred overnight at 95 C. The reaction liquid was cooled, aqueous ammonia was added thereto and extracted with ethyl acetate, washed with saturated saline water and dried with anhydrous magnesium sulfate. The solvent was evaporated away under reduced pressure, and crystallized with ethyl acetate to obtain the entitled compound as a white solid Step 2) Production of 2-allyl-1-[6-(1-hydroxy-1-methylethyl)-2-pyridinyl]-6-(methylthio)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one The entitled compound was obtained in the same manner as in Preparative Example 1-1, for which, however, the compound obtained in the above reaction was used in place of 2-iodopyridine used in Preparative Example 1-1. 1H-NMR (400 MHz, CDCl3) delta: 8.95 (1H, s), 7.91 (1H, t, J=8.0 Hz), 7.76 (1H, d, J=7.3 Hz), 7.40 (1H, dd, J=7.8, 1.0 Hz), 5.70 (1H, ddt, J=17.1, 10.2, 6.3 Hz), 5.06 (1H, dd, J=10.2, 1.0 Hz), 4.93 (1H, dd, J=17.1, 1.2 Hz), 4.81 (2H, d, J=6.3 Hz), 2.59 (4H, s), 1.59 (6H, s). ESI-MS Found: m/z[M+H]+:358.
With copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 80 - 95℃; for 18h; General method for the preparation of pyridyl pyrazolopyrimidinones (9a-c). Nu,Nu'- Dimethylethylenediamine (4.47 mmol) was added to a solution of pyrazolopyrimidine 7 (2.25 mmol), bromopyridine (8a-c; 2.93 mmol), copper iodide (2.25 mmol) and K2C03 (3.1 5 mmol) in 1 ,4-dioxane (5 ml) at 80 C. The resultant suspension was heated at 95 C for 18 h, over which time a colour change of orange to dark green occurred. The reaction mixture was cooled to RT and diluted with NH40H (10 ml) before being extracted with EtOAc (2 x 20 ml). The combined organic extracts were washed with brine (20 ml), dried 33 (MgS04) and evaporated to dryness. The crude material was purified via silica gel chromatography (19:1 DCM:MeOH) to afford the target pyridyl pyrazolopyrimidinones (69-84%). 2-Allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-(methylthio)-1,2-dihydro-3H- pyrazolo[3,4- d]pyrimidin-3-one (9a). Rf 0.63 (9:1 DCM:MeOH); M.p.108-111 C; IR (cm-1) 3337, 3081, 2966, 2924, 1663, 1601, 1559; 1H NMR(400 MHz, CDCI3) 1.61 (6H, s, C(CH3)2), 2.61 (3H, s, S-CH3), 3.77 (1H, s, -OH), 4.82 (2H, dapp, J = 5.9 Hz, N2-CH2), 4.95 (1H, dapp, J = 16.9 Hz, allyl C-Htrans), 5.08 (1H, dapp, J = 10.3 Hz, allyl C-Hcis), 5.72 (1H, dd = 16.9, 10.3, 5.9 Hz, allyl C-H), 7.42 (1H, d, J = 7.7 Hz, H-5'), 7.78 (1H, d,J = 8.0 Hz, H-3'), 7.93 (1H, dd,J = 8.0, 7.7 Hz, H-4'), 8.96 (1H, s, H-4); 13C NMR(125 MHz, CDCI3) 14.5 (SCH3), 30.5 (C(CH3)2), 47.5 (N2-CH2), 72.5 (C(CH3)2), 116.4 (Ar-C), 116.6 (Ar-C), 119.3 (allyl-CH2), 131.2, 139.2, 147.0 (Ar-C), 154.3 (Ar-C), 159.2 (C=0), 161.0 (Ar-C), 166.1 (Ar-C), 177.0 (Ar-C); MS [M + H]+ m/z 359.3.
1.8 g With copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine; In 1,4-dioxane; at 100℃; for 12h;Inert atmosphere; Compound N1, N2-dimethylethane-1,2-diamine (872 mg) was added to compound S-4 (2g), and 2- (6-bromopyridin-2-yl) propan-2-ol ( 2.3 g), CuI (1.7 g) and potassium carbonate (2.5 g) in 1,4-dioxane (25 mL). Heat to 100 C under nitrogen and stir for 12 hours. After cooling to room temperature, a saturated ammonium chloride solution (50 mL) was added to the reaction system, and extracted with DCM. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (DCM / MeOH, 45: 1, v / v) to give the target product Int-1 (1.8 g) as a pale yellow solid

  • 2
  • [ 955369-56-9 ]
  • [ 33322-60-0 ]
  • 3-((2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-3-oxo-2,3-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)-N,N-dimethylbenzamide [ No CAS ]
  • 3
  • [ 69189-26-0 ]
  • [ 955369-56-9 ]
  • 2-allyl-1-(6-(2-hydroxypropane-2-yl)pyridin-2-yl)-6-((2-methyl-3-oxoisoindolin-5-yl)amino)-1H-pyrazolo[3,4-d]pyrimidin-3(2H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
2.6mg To a toluene solution (5 mL) of compound Int-1 (100 mg), m-CPBA (146 mg) was added and stirred at room temperature overnight to obtain a solution A. NaH (56 mg) was added to a DMF (5 mL) solution in which Compound A-31 (59 mg) was dissolved, and stirred at room temperature for 30 minutes to obtain a mixture B. Then A was slowly added to B and stirred overnight at room temperature. The reaction solution was poured into a saturated ammonium chloride solution, a white solid was precipitated, and the filter cake was purified by thin layer chromatography TLC (dichloromethane: methanol (v / v) = 20: 1) to obtain the standard product HY-B031 (2.6 mg) as a white solid.
 

Historical Records

Technical Information

• Acyl Group Substitution • Appel Reaction • Baeyer-Villiger Oxidation • Barbier Coupling Reaction • Baylis-Hillman Reaction • Bucherer-Bergs Reaction • Buchwald-Hartwig C-N Bond and C-O Bond Formation Reactions • Chan-Lam Coupling Reaction • Chugaev Reaction • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Bakshi-Shibata (CBS) Reduction • Corey-Chaykovsky Reaction • Corey-Kim Oxidation • Dess-Martin Oxidation • Fischer Indole Synthesis • Grignard Reaction • Henry Nitroaldol Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Jones Oxidation • Lawesson's Reagent • Leuckart-Wallach Reaction • Martin's Sulfurane Dehydrating Reagent • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Mitsunobu Reaction • Moffatt Oxidation • Nucleophilicity of Sulfur Compounds • Oxidation of Alcohols by DMSO • Oxidation States of Sulfur Compounds • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Peterson Olefination • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Alcohols • Preparation of Aldehydes and Ketones • Preparation of Amines • Prins Reaction • Reactions of Alcohols • Reactions of Aldehydes and Ketones • Reactions of Amines • Reactions with Organometallic Reagents • Reformatsky Reaction • Ritter Reaction • Robinson Annulation • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Sharpless Olefin Synthesis • Specialized Acylation Reagents-Carbodiimides and Related Reagents • Specialized Acylation Reagents-Ketenes • Stobbe Condensation • Swern Oxidation • Tebbe Olefination • Ugi Reaction • Wittig Reaction • Wolff-Kishner Reduction

Categories

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[ 955369-56-9 ]

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