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Chemical Structure| 3651-67-0 Chemical Structure| 3651-67-0

Structure of 3651-67-0

Chemical Structure| 3651-67-0

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Product Details of [ 3651-67-0 ]

CAS No. :3651-67-0
Formula : C5H12ClNO
M.W : 137.61
SMILES Code : CN1CCOCC1.[H]Cl
MDL No. :MFCD00039042
InChI Key :BTJRKNUKPQBLAL-UHFFFAOYSA-N
Pubchem ID :3083815

Safety of [ 3651-67-0 ]

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

Computational Chemistry of [ 3651-67-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 38.9
TPSA ?

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

12.47 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

0.47
Log Po/w (WLOGP)?

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

0.37
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.

0.21
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

0.94
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.4

Water Solubility

Log S (ESOL):?

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

-0.99
Solubility 14.1 mg/ml ; 0.103 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-0.3
Solubility 68.8 mg/ml ; 0.5 mol/l
Class?

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

Very 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

-0.38
Solubility 57.9 mg/ml ; 0.421 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

Low
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.

-6.81 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)

1.35

Application In Synthesis of [ 3651-67-0 ]

* 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 [ 3651-67-0 ]

[ 3651-67-0 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 17612-91-8 ]
  • [ 27486-87-9 ]
  • [ 3651-67-0 ]
  • [ 311343-00-7 ]
YieldReaction ConditionsOperation in experiment
55% With 4-methyl-morpholine; isobutyl chloroformate; In ethyl acetate; at -15 - 20℃; for 3.5h; A solution comprising 290 mg (0.71 mmol) of <strong>[27486-87-9]N-acetyl-S-trityl-L-cysteine</strong> (7, Bachem) and 80 mul (0.72 mmol) of of N-methylmorpholine (NMM) in 5 ml of AcOEt is stirred at -15 C. and then 93 mul (0.71 mmol) of isobutyl chloroformate are added. After stirring for 15 min and while maintaining the starting temperature, 111.4 mg (0.71 mmol) of S-acetylcysteamine hydrochloride (prepared according to T. Wieland and E. Bokelman, Ann. Chem., 1952, 576, 20-34) and then 80 mul (0.72 mmol) of NMM are added. The reaction mixture is maintained at -15 C. for 15 min and then, after returning to room temperature, stirring is continued for 3 h. The NMM hydrochloride formed is filtered off and washed with 2×2.5 ml of AcOEt and the combined organic phases are evaporated to dryness under vacuum. The coupling product is subsequently isolated from the gum obtained by flash chromatography on a silica gel column (eluent: AcOEt/petroleum ether 30%). 198 mg (Yd=55%) of the expected compound are collected. Rf (AcOEt/petroleum ether, 9:1): 0.41. Cystallizes from an AcOEt/petroleum ether mixture in the form of a colorless powder: M.p.=111-113 C. [alpha]D20=+10.5 (c 0.8, CHCl3). [0155] 1H NMR (CDCl3) delta ppm: 1.90 (s, 3H, NCOCH3), 2.29 (s, 3H, SCOCH3), 2.48 (dd, J=5.7, 12.9 Hz, 1H, beta Ha cys), 2.82 (dd, J=6.4, 12.9 Hz, 1H, beta Hb cys), 2.92-3.01 (m, 2H, NCH2CH2S), 3.32-3.42 (m, 2H, NCH2CH2S), 4.07-4.20 (m, 1H, alpha H cys), 5.70 (d, J=7.6 Hz, 1H, NH cys), 6.34 (t, J=5.5 Hz, 1H, NHCH2), 7.19-7.35 and 7.40-7.47 (2 m, 15H, aromatic H). MS: (FAB+/NBA+K+) m/z 545 (M+K)+, 507 (M+H)+; (FAB-/NBA) m/z 505 (M-H)-. [TABLE-US-00001] Analysis: C28H30N2O3S2 (506) Calc. %: C 66.40 H 5.93 N 5.53 Found %: 66.17 6.00 5.81
  • 2
  • [ 6066-82-6 ]
  • [ 27486-87-9 ]
  • [ 3651-67-0 ]
  • [ 73609-53-7 ]
YieldReaction ConditionsOperation in experiment
With 4-methyl-morpholine; isobutyl chloroformate; In ethyl acetate; at -15℃; for 2.5h; A solution comprising 1.5 g (3.70 mmol) of 7 and 410 mul (3.73 mmol) of NMM in 30 ml of AcOEt is stirred at -15 C. and then 480 mul (3.70 mmol) of isobutyl chloroformate are added. After stirring for 15 min and while maintaining the starting temperature, 426 mg (3.70 mmol) of N-hydroxysuccinimide are added. The reaction mixture is maintained at -15 C. for 15 min and then, after returning to ambient temperature, stirring is continued for 2 h. The NMM hydrochloride formed is filtered off and washed with 2×5 ml of AcOEt. The organic phases comprising the O-N-succinimide active ester of 7 are combined and stirred at -15 C. 575 mg (3.70 mmol) of S-acetylcysteamine hydrochloride and 410 mul (3.73 mmol) of NMM are then successively added to the solution. The reaction mixture is maintained at -15 C. for 15 min and then, after returning to ambient temperature, stirring is continued for 12 h. The solution is subsequently diluted with 300 ml of AcOEt, washed (water, 30 ml; ice-cold saturated sodium bicarbonate, 30 ml; water, 30 ml; ice-cold 0.1N citric acid, 30 ml; water, 3×30 ml), dried over sodium sulfate, filtered and evaporated to dryness under vacuum. The residue obtained is subsequently purified as above to give, with a yield of 70% (1.31 g) and with entirely the same physicochemical criteria, the coupling product 8 described above.
 

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