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Chemical Structure| 582313-57-3 Chemical Structure| 582313-57-3

Structure of 582313-57-3

Chemical Structure| 582313-57-3

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Product Details of [ 582313-57-3 ]

CAS No. :582313-57-3
Formula : C6H3ClFN3
M.W : 171.56
SMILES Code : FC1=CNC2=NC=NC(Cl)=C21
MDL No. :MFCD12924542
InChI Key :OOBFPXOXHUBRDN-UHFFFAOYSA-N
Pubchem ID :11321224

Safety of [ 582313-57-3 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 582313-57-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 9
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 38.86
TPSA ?

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

41.57 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.45
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

1.72
Log Po/w (WLOGP)?

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

2.17
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.

1.21
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

2.63
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.84

Water Solubility

Log S (ESOL):?

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

-2.59
Solubility 0.438 mg/ml ; 0.00255 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.

-2.21
Solubility 1.06 mg/ml ; 0.00618 mol/l
Class?

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

-3.43
Solubility 0.0639 mg/ml ; 0.000372 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

Yes
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

Yes
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.

-6.13 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

1.0
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)

1.65

Application In Synthesis of [ 582313-57-3 ]

* 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.

  • Downstream synthetic route of [ 582313-57-3 ]

[ 582313-57-3 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 163226-45-7 ]
  • [ 582313-57-3 ]
  • C34H29ClFN3O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 0.5h; To a mixture of compound 1 (318 mg, 0.74 mmol), compound 2 (140 mg, 0.82 mmol) and Ph3P (388 mg, 1.48 mmol) in THF (30 mL) was added DIAD (299 mg, 1.48 mmol) at 0 0C. After stirring 30 min at rt, the mixture was evaporated and purified by column <n="63"/>chromatography on a silica gel. The appropriate fraction was collected and evaporated. The residue was treated with saturated methanolic ammonia and heated to 80 C for 16h. After cooling, the mixture was purified by column chromatography on a silica gel to give 6 (350 mg, 84 %) as a white solid, mp : 100 - 102 0C; [alpha]27D -25.33 (c 0.13, CHCl3); 1H NMR (500 MHz, CDCl3) delta 8.33 (s, IH), 7.4 - 7.5 (m, 6H), 7.2 - 7.35 (m, 9H), 6.48 (d, J= 2.0 Hz, IH), 5.99 (s, IH), 5.88 (s, IH), 5.37 (s, 2H), 5.18 (d, J= 6.0 Hz, IH), 4.54 (d, J= 6.0 Hz, IH), 4.01 (dt, J= 15 and 2 Hz, IH), 3.83 (d, J= 15.5 Hz, IH), 1.42 (s, 3H), 1.30 (s, 3H); 13C NMR (100 MHz, CDCl3) 155.51, 155.49, 153.20, 149.12, 145.84, 145.81, 144.14, 143.78, 141.71, 128.54, 128.09, 127.94, 127.20, 123.07, 112.48, 104.25, 103.99, 93.81, 93.66, 87.26, 84.99, 83.94, 77.24, 63.97, 61.48, 27.52, 26.10. UV (CHCl3) lambdamax 283.0 nm; Anal. Calcd. for (C34H31FN4O3-O^CHCl3) C 68.37, H 5.24, N 9.29 Found C 68.40, H 5.17, N 9.08.
  • 2
  • [ 64-18-6 ]
  • [ 1228947-14-5 ]
  • [ 582313-57-3 ]
  • 4-((trans)-4-((5-fluoro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)cyclohexyl)morpholine*0.58(formic acid) [ No CAS ]
YieldReaction ConditionsOperation in experiment
To a solution of trans-4-(morpholin-4-yl)cyclohexan-l-ol (550 mg, 2.97 mmol, 5.09 equiv) in tetrahydrofuran (10 mL) was added sodium hydride (600 mg, 15.00 mmol, 25.73 equiv, 60%)). After stirring for 30 min at 0C, 4-chloro-5-fluoro-7H-pyrrolo[2,3-d]pyrimidine (100 mg, 0.58 mmol, 1.00 equiv) was added. The resulting solution was heated to reflux overnight and then quenched by the addition of 2 mL of water. The resulting mixture was concentrated under vacuum. The crude product (80 mg) was purified by Prep-HPLC with the following conditions: Column, SunFire Prep CI 8, 19* 150mm 5um; mobile phase, water with 50mL HCOOH and CH3CN (5.0% CH3CN up to 43.0% in 10 min, up to 90.0% in 3 min, down to 5.0% in 3 min); Detector, 220/254nm. This resulted in 29.8 mg (14%) of 4-((trarcs)-4-((5-fluoro-7H-pyrrolo[2,3- d]pyrimidin-4-yl)oxy)cyclohexyl)morpholine as an off-white solid. LC-MS: (ES,m/z): 321 [M+H]+ . 1H NMR (300 MHz, CD3OD, ppm): delta 1.60-1.40 (m, 4H), 2.11-2.15 (m, 2H), 2.32-2.35 (m, 2H), 2.64-2.67 (m, 1H), 2.84-2.87 (m, 4H), 3.77-3.82 (m, 4H), 5.20-5.27 (m, 1H), 6.98 (d, 1H), 8.28 (s, 1H), 8.40-8.45 (brs, 0.58H).
 

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