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Chemical Structure| 28783-38-2 Chemical Structure| 28783-38-2

Structure of 28783-38-2

Chemical Structure| 28783-38-2

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Product Details of [ 28783-38-2 ]

CAS No. :28783-38-2
Formula : C7H10ClNS
M.W : 175.68
SMILES Code : C12=C(C=CS2)CCNC1.[H]Cl
MDL No. :MFCD08448167
InChI Key :VQEOIFRMJGFLQH-UHFFFAOYSA-N
Pubchem ID :25067333

Safety of [ 28783-38-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 28783-38-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 5
Fraction Csp3 0.43
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 50.63
TPSA ?

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

40.27 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

1.84
Log Po/w (WLOGP)?

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

1.66
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.

1.53
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

3.22
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.65

Water Solubility

Log S (ESOL):?

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

-2.46
Solubility 0.611 mg/ml ; 0.00348 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.

-2.31
Solubility 0.868 mg/ml ; 0.00494 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

-2.52
Solubility 0.531 mg/ml ; 0.00302 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

Yes
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.

-6.07 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)

2.06

Application In Synthesis of [ 28783-38-2 ]

* 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 [ 28783-38-2 ]

[ 28783-38-2 ] Synthesis Path-Downstream   1~9

  • 1
  • [ 2942-58-7 ]
  • [ 5581-75-9 ]
  • [ 28783-38-2 ]
  • 1-(5,7-dihydro-4H-thieno[2,3-c]pyridin-6-yl)-6-phenylhexan-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In dichloromethane; g) Synthesis of 1-(5,7-dihydro-4H-thieno[2,3-c]pyridin-6-yl)-6-phenylhexan-1-one To a solution of 0.272 g (1.548 mmol) of <strong>[28783-38-2]4,5,6,7-tetrahydrothieno[2,3-c]pyridine hydrochloride</strong>, 0.33 g (1.7 mmol) of 6-phenylhexanoic acid and 0.86 ml (6.2 mmol) of triethylamine in 30 ml of dichloromethane, 0.28 ml (1.9 mmol) of diethyl cyanophosphonate was added dropwise under ice-cooling, followed by overnight stirring at room temperature. The reaction mixture was poured into aqueous sodium hydroxide and extracted with dichloromethane 3 times. The combined organic layer was dried over anhydrous magnesium sulfate; the solvent was distilled off under reduced pressure. The resulting crude product was purified by silica gel column chromatography (hexane/ethyl acetate=6/1 to 3/1) to yield the desired product. Colorless oil Yield 0.503 g (100%) 1 H-NMR (CDCl3, 200 MHz) delta1.340-1.478 (2H, m), 1.577-1.789 (4H, m), 2.340-2.450 (2H, m), 2.573-2.786 (4H, m), 3.690 (1.2H, t, J=5.7 Hz), 3.868 (0.8H, t, J=5.8 Hz), 4.654 (0.8H, s), 4.800 (1.2H, s), 6.775-6.821 (1H, m), 7.134-7.314 (6H, m); IR (neat) 2929, 1645, 1427, 1227, 702 cm-1
  • 2
  • [ 165947-52-4 ]
  • [ 28783-38-2 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In methanol; f) Synthesis of 4,5,6,7-tetrahydrothieno[2,3-c]pyridine hydrochloride To a solution of 1.427 g (5.962 mmol) of 6-tert-butoxycarbonyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine in 5 ml of methanol, 3 ml of concentrated hydrochloric acid was added, followed by stirring at room temperature for 1 hour. The solvent was distilled off under reduced pressure to yield the desired product. White crystal Yield 1.025 g (98%) 1 H-NMR (CD3 OD, 200 MHz) delta3.022 (2H, tt, J=1.6&6.2 Hz), 3.507 (2H, t, J=6.3 Hz), 4.430 (2H, s), 6.915 (1H, d, J=5.0 Hz), 7.386 (1H, d, J=5.2 Hz); IR (nujol) 2777-2416, 1157, 1090, 1036, 702 cm-1; Anal. Calcd for C7 H10 ClNS: C, 47.86; H, 5.74; N, 7.97. Found: C, 47.82; H, 5.63; N, 8.02.
  • 3
  • [ 24424-99-5 ]
  • [ 28783-38-2 ]
  • 5-t-butoxycarbonyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% With triethylamine;dmap; In ethyl acetate; N,N-dimethyl-formamide; (a) To the solution of <strong>[28783-38-2]4,5,6,7-tetrahydrothieno[2,3-c]pyridine hydrochloride</strong> (5.2 g) in DMF (60 ml) were added di-t-butyl dicarbonate (7.11 g), triethylamine (6.58 g) and a catalytic amount of 4-dimethylaminopyridine, and the mixture was stirred at room temperature for 1 hour. After the addition of ethyl acetate (300 ml) and washed with saturated saline, the mixture was dried over anhydrous magnesium sulfate. The solvent was removed by distillation. The residue was purified by column chromatography on silica gel to give 4.67 g of 5-t-butoxycarbonyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine from the fraction eluted with n-hexane:ethyl acetate=2:1 (yield, 88%). 1 H-NMR (CDCl3) delta:1.48 (s, 9H), 2.70 (brs, 2H), 3.68 (brs, 2H), 4.62 (brs, 2H), 6.79 (d, J=5 Hz, 1H), 7.13 (d, J=5 Hz, 1H). FDMS (m/z): 239 (M+).
  • 4
  • [ 28783-38-2 ]
  • 2-bromo-4,5,6,7-tetrahydrothieno[2,3-c]pyridine hydrobromide [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With bromine; In acetic acid; at 20℃; for 1.5h; A solution of bromine (139 mg, 0.87 mmol) in acetic acid (0.5 mL) was added to a solution of <strong>[28783-38-2]4,5,6,7-tetrahydrothieno[2,3-c]pyridine hydrochloride</strong> (150 mg, 0.85 mmol) in acetic acid (3 mL) and the mixture left to stir at ambient temperature for 1.5 h. The resultant precipitate was collected by filtration, washed with diethyl ether and left to air dry to afford the title compound as an off-white solid (230 mg, 90%). 1H NMR (DMSO-D6, 300MHz): 9.19 (s, 2H), 7.09 (s, 1H), 4.29-4.26 (m, 2H), 2.86-2.78 (m, 2H), 2.52-2.48 (m, 2H). LCMS (Method B): RT= 1.65 min, M+H+ = 218/220.
  • 5
  • [ 1323407-86-8 ]
  • [ 28783-38-2 ]
  • [ 1323403-95-7 ]
YieldReaction ConditionsOperation in experiment
74% With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 20℃; 5.109 3-{4-[4-(4,7-DIHYDRO-5H-THIENO[2,3-C]PYRIDIN-6-YLMETHYL)-BENZYLOXY]-1-OXO-1,3-DIHYDRO-ISOINDOL-2-YL}-PIPERIDINE-2,6-DIONE To the CH3CN (10 ml) solution of 3-(4-(4-(bromomethyl)benzyloxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (0.359 g, 0.810 mmol) was added <strong>[28783-38-2]4,5,6,7-tetrahydrothieno[2,3-c]pyridine hydrochloride</strong> (0.171 g, 0.972 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.402 ml, 2.430 mmol). It became a clear solution after DIPEA was added. The mixture was stirred at room temperature overnight. Solvent was evaporated and to the residue was added methylene chloride (80 ml). The mixture was washed with water (2*60 ml), brine (50 ml), dried and concentrated to an off-white solid, which was purified by silica gel column (MeOH/CH2Cl2) to give 3-{4-[4-(4,7-Dihydro-5H-thieno[2,3-c]pyridin-6-ylmethyl)-benzyloxy]-1-oxo-1,3-dihydro-isoindol-2-yl}-piperidine-2,6-dione as a white solid (0.304 g, 74% yield). HPLC: Waters Symmetry C-18, 3.9*150 mm, 5 mum, 1 mL/min, 240 nm, gradient from 10/90 to 90/10 in 5 min, isocratic at 90/10 for 5 min (CH3CN/0.1% H3PO4), 4.61 min (98.1%). 1H NMR (DMSO-d6) delta 1.89-2.08 (m, 1H, CHH), 2.35-2.48 (m, 1H, CHH), 2.53-2.68 (m, 3H, CHH, CH2), 2.68-2.77 (m, 2H, CH2), 2.82-3.00 (m, 1H, CHH), 3.59 (s, 2H, CH2), 3.68 (s, 2H, CH2), 4.20-4.48 (m, 2H, CH2), 5.11 (dd, J=5.2, 13.3 Hz, 1H, NCH), 5.24 (s, 2H, CH2), 6.82 (d, J=5.1 Hz, 1H, Ar), 7.28 (d, J=5.1 Hz, 1H, Ar), 7.31-7.42 (m, 4H, Ar), 7.43-7.56 (m, 3H, Ar), 10.97 (s, 1H, NH). 13C NMR (DMSO-d6) delta 22.36, 25.12, 31.20, 45.10, 49.59, 51.36, 51.59, 60.50, 69.45, 115.00, 115.24, 122.61, 126.99, 127.72, 128.83, 129.81, 129.95, 132.46, 133.32, 133.47, 135.35, 138.29, 153.53, 168.01, 170.96, 172.82. LC/MS m/e=502. Anal Calcd for C28H27N3O4S (+0.5 H2O): C, 65.86; H, 5.53; N, 8.23. Found: C, 65.64; H, 5.44; N, 8.04.
  • 6
  • [ 24424-99-5 ]
  • [ 28783-38-2 ]
  • [ 165947-52-4 ]
YieldReaction ConditionsOperation in experiment
100% With triethylamine; In dichloromethane; at 20℃; for 4.5h; 4,5,6,7-tetrahydrothiophene[2,3-c]pyridine hydrochloride (15.0g, 85.38mmol) and triethylamine (24.0mL, 170.77mmol) was dissolved in In dichloromethane (150mL), was added di-tert-butyl dicarbonate (22.36g, 102.46mmol). It was stirred at roomtemperature for 4.5 hours. After completion of the reaction, Was added water (50mL), (30mL × 2) and extracted withdichloromethane. The combined organic phases were washed with water (20mL × 2), saturated brine (30 mL) , Dried over anhydrous sodium sulfate. Filtered and the solvent evaporated under reduced pressure and the crude product purified bycolumn chromatography (petroleum ether/ethyl acetate (v/v=20/1), obtained as a white solid (20.49g, 100%).
  • 7
  • [ 28783-38-2 ]
  • [ 1200131-56-1 ]
  • 8
  • [ 1401031-28-4 ]
  • [ 28783-38-2 ]
  • (R)-6-(2-(9-(pyridin-2-yl)-6-oxaspiro[4.5]decan-9-yl)ethyl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
10% (R)-2-(9-(Pyridin-2-yl)-6-oxa[4.5]decane-9-yl)acetaldehyde (21B) (0.259 g, 1.0 mmol) was dissolved in dichloromethane. 36mL)In the middle, sodium sulfate (1.42g, 5.0mmol)and4,5,6,7-4,5,6,7 tetrahydroisothiophene [3, 2-c]pyridine hydrochloride(0.22 g, 1.25 mmol) was added to the reaction, which was reacted overnight at room temperature.Sodium borohydride (0.048 g, 1.25 mmol) was added to the reaction.The reaction was stirred for 30 minutes, then methanol (10 mL) was added and the mixture was stirred for 1 hour.The reaction was quenched with water (30 mL) andEtOAc.The combined organics were washed with saturated sodium chloride (30 mL)Dry over anhydrous sodium sulfate, filter, and concentrate the filtrate.Column chromatography on crude material (dichloromethane/methanol (v/v) = 40:1 to 20:1)Yellow oily liquid(R)-5-(2-(9-(pyridin-2-yl)-6-oxaspiro[4.5]decane-9-yl)ethyl)-4,5,6,7 tetrahydroisothiophene [3,2-c]pyridine (22A)(0.050 g, yield 10%).
  • 9
  • [ 223123-46-4 ]
  • [ 28783-38-2 ]
  • [ 113665-84-2 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; at 25 - 40℃; for 24.0h; Add in 2L reaction bottle at 25~35C4,5,6,7-tetrahydrothienopyridine hydrochloride 170.0 g, 30% potassium carbonate 897.5 g,And a solution of methyl 2-benzenesulfonate-2-(2-chlorophenyl)acetate in 340.0 g,After the completion of the dropwise addition, the mixture was stirred at 40 C for 24 hours. Down to room temperature,The organic phase was washed with water and dried over anhydrous sodium sulfate. Evaporating the solvent to obtain an oily liquid,215.3 g of dichloromethane was recovered to obtain 338 g of clopidogrel free base.The yield was 95.9% and the purity was 93.42%.
 

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