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Chemical Structure| 23784-96-5 Chemical Structure| 23784-96-5

Structure of 23784-96-5

Chemical Structure| 23784-96-5

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Product Details of [ 23784-96-5 ]

CAS No. :23784-96-5
Formula : C5H4Cl2S
M.W : 167.06
SMILES Code : ClCC1=CC=C(Cl)S1
MDL No. :MFCD00009764
InChI Key :MQTKXCOGYOYAMW-UHFFFAOYSA-N
Pubchem ID :583079

Safety of [ 23784-96-5 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H314-H290
Precautionary Statements:P501-P260-P234-P264-P280-P390-P303+P361+P353-P301+P330+P331-P363-P304+P340+P310-P305+P351+P338-P310-P406-P405
Class:8
UN#:3265
Packing Group:

Computational Chemistry of [ 23784-96-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 5
Fraction Csp3 0.2
Num. rotatable bonds 1
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 39.09
TPSA ?

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

28.24 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.16
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

2.99
Log Po/w (WLOGP)?

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

2.99
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.

2.53
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

4.15
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.96

Water Solubility

Log S (ESOL):?

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

-3.16
Solubility 0.117 mg/ml ; 0.000698 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.

-3.25
Solubility 0.0946 mg/ml ; 0.000566 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

-3.3
Solubility 0.0845 mg/ml ; 0.000506 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.

-5.2 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

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)

2.43

Application In Synthesis of [ 23784-96-5 ]

* 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 [ 23784-96-5 ]

[ 23784-96-5 ] Synthesis Path-Downstream   1~35

  • 4
  • [ 23784-96-5 ]
  • [ 93-30-1 ]
  • (5-chloro-[2]thienylmethyl)-[2-(2-methoxy-phenyl)-1-methyl-ethyl]-methyl-amine [ No CAS ]
  • 5
  • [ 23784-96-5 ]
  • [ 156-57-0 ]
  • 2-<(5-Chlor-2-thenyl)thio>ethylamin [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium; In hydrogenchloride; methanol; a 2-[(5-Chloro-2-thenyl)thio]ethylamine STR204 3.41 g (30 mmol) of cysteamine hydrochloride are introduced under a current of nitrogen into a solution of 1.38 g (60 mmol) of sodium in 100 ml of methanol. 5.01 g (30 mmol) of 5-chloro-2-(chloromethyl)thiophene are added after 10 minutes, stirring at room temperature. The solvent is distilled off under vacuum after one hour and the residue is dissolved in 5% hydrochloric acid and extracted with ether. After alkalization with sodium hydroxide solution, the aqueous phase is extracted by shaking with methylene chloride and the organic phase is washed with water, dehydrated over sodium sulphate and concentrated by evaporation under vacuum. The oily amine base left as residue is converted into the hydrochloride by reaction with ethanolic hydrochloric acid and recrystallized from ethanol/water.
  • 6
  • [ 23784-96-5 ]
  • potassium β-diethoxyphosphoryl-β-cyanoethylene dithiolate [ No CAS ]
  • β-diethoxyphosphoryl-β-cyano-bis-S,S-(5-chlorothienyl-2-methylthio)keteneacetal [ No CAS ]
  • 7
  • [ 23784-96-5 ]
  • 4-(4-Hydroxy-phenyl)-pyrrolidin-2-one [ No CAS ]
  • 4-[4-(5-Chloro-thiophen-2-ylmethoxy)-phenyl]-pyrrolidin-2-one [ No CAS ]
  • 8
  • [ 23784-96-5 ]
  • [ 201230-82-2 ]
  • [ 23222-34-6 ]
  • 9
  • [ 23784-96-5 ]
  • tris[(5-chloro-2-thienyl)methyl]phosphine oxide [ No CAS ]
  • 11
  • [ 5463-09-2 ]
  • [ 23784-96-5 ]
  • [ 1027909-56-3 ]
  • 13
  • [ 23784-96-5 ]
  • [ 955921-01-4 ]
  • C23H25ClN4OS [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene on polystyrene.HL; In acetonitrile; at 120℃; for 0.333333h;microwave irradiation; Preparation of final compound 13-2; Compound 14-1 (31 mg, 0.1 mmol), 2-chloro-5-(chloromethyl) thiophene (0.2 mmol), and PS-TBD (100 mg, 0.3 mmol) were suspended in CH3CN (2 ml). The reaction was heated in the microwave at 120 0C for 20 minutes. The resin was filtered off, and the filtrate was concentrated under vacuum. The resulting crude was purified by HPLC yielding 0.029 g of the purified final compound 13-2 (65 %).
  • 14
  • [ 23784-96-5 ]
  • [ 958445-81-3 ]
  • C21H22ClFN4O2S [ No CAS ]
YieldReaction ConditionsOperation in experiment
69% With C15H20N3Pol; In acetonitrile; at 120℃; for 0.333333h;microwave irradiation; Final compound 13-1 (31 mg, 0.1 mmol), 2-chloro-5-(chloromethyl) thiophene (0.2 mmol), and PS-TBD (100 mg, 0.3 mmol) were suspended in CH3CN (2 ml). The reaction was heated in the microwave at 120 0C for 20 minutes. The resin was filtered off, and the filtrate was concentrated under vacuum. The resulting crude was purified by HPLC yielding 0.027 g of the purified final compound 12-2 (69 %).
  • 15
  • [ 23784-96-5 ]
  • C16H20N4O [ No CAS ]
  • C21H23ClN4OS [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene on polystyrene.HL; In acetonitrile; at 120℃; for 0.333333h;Microwave irradiation; m) Preparation of final compound 10-1 1; Intermediate compound I-9 (28 mg, 0.1 mmol), <strong>[23784-96-5]2-chloro-5-(chloromethyl)thiophen</strong>e (0.2 mmol) and PS-TBD (103 mg, 0.3mmol) were suspended in CH3CN (2 ml). The reac- <n="43"/>tion was heated in the microwave at 120 0C for 20 minutes. The resin was filtered off, and the filtrate was concentrated under vacuum. The resulting crude was purified by HPLC yielding 0.031 g of the purified final compound 10-11 (75 %).
  • 18
  • [ 23784-96-5 ]
  • [ 1026609-90-4 ]
  • 19
  • [ 23784-96-5 ]
  • 2-Butylamino-8-hydroxy-9-(5-chloro-2-thienylmethyl)adenine [ No CAS ]
  • 20
  • [ 23784-96-5 ]
  • [ 1053662-88-6 ]
  • 21
  • [ 23784-96-5 ]
  • (2S,3S,4R,5R)-5-(6-{2-[1-(5-Chloro-thiophen-2-ylmethyl)-1H-indol-3-yl]-ethylamino}-purin-9-yl)-3,4-dihydroxy-tetrahydro-furan-2-carboxylic acid cyclopropylamide [ No CAS ]
  • 22
  • [ 23784-96-5 ]
  • 4-Amino-3-[4-(5-chloro-thiophen-2-ylmethoxy)-phenyl]-butyric acid [ No CAS ]
  • 26
  • [ 23784-96-5 ]
  • [ 74214-62-3 ]
  • C19H15ClN2O2S [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium hydride; In DMF (N,N-dimethyl-formamide); at 20℃; for 21h; To a stirred solution of ethyl 9H-O-carboline-3-carboxylate (300 mg, 1.25 mmol) in DMF (3 mL) under a nitrogen atmosphere was added NaH (50.0 mg, 60% in mineral oil, 1.25 mmol) portionwise, followed by 2-chloro-5-(chloromethyl)-thiophene (151 μL, 1.25 mmol). The stirring was continued for 21 hours at ambient temperature, water (50 mL) was then added to the mixture. The precipitate was filtered, washed with water and dried to give a solid that was dissolved in methanol (25 mL). To the resulting solution, H2NOH (25 mL, 50 wt. % solution in H2O, 0.38 mol) was added. The suspension was stirred for 4 days at ambient temperature. The mixture was then filtered, and the solid was boiled in methanol (25 mL). After filtration, the desired product (0.26 g, 58%) was obtained. 1H NMR (400 MHz, DMSO-d6): 11.28 (1H, s), 9.15 (1H, s), 9.01 (1H, s), 8.81 (1H, s), 8.44 (1H, d, J=8 Hz), 6.94-7.92 (5H, m), 5.99 (2H, s). HRMS (M+H)+ found: 358.0417. Calcd for C17H13N3O2SCl: 358.0417.
  • 27
  • [ 23784-96-5 ]
  • [ 452-12-0 ]
  • 3-[(5-chloro-thiophen-2-yl)methyl]thio}-6-ethyl-1,2,4-triazin-5(2H)-one hydrochloride [ No CAS ]
  • 28
  • [ 23784-96-5 ]
  • [ 91-56-5 ]
  • [ 445455-63-0 ]
YieldReaction ConditionsOperation in experiment
22% A solution of isatin (125 mg, 0.85 mmol) in anhydrous dioxane (10 mL) was added dropwise to a solution of sodium hydride (60% dispersion in mineral oil, 24 mg, 0.62 mmol) in anhydrous dioxane (10 mL) at 0 C. under argon. The mixture was allowed to stir for 5 minutes and then <strong>[23784-96-5]2-chloro-5-(chloromethyl)thiophen</strong>e (0.12 mL, 1.02 mmol) in dioxane (10 mL) was added dropwise to the resulting mixture. The reaction mixture was heated at reflux under argon for 16 h and concentrated in vacuo. The crude material was purified by preparative TLC using 1:24 methanol in chloroform as the eluent, giving the desired product as a yellow solid (53 mg, 0.19 mmol, 22%). 1H NMR (400 MHz): δ 7.62 (d, J=7.4, 1H), 7.56 (t, J=7.8, 11H), 7.14 (t, J=7.7, 1H), 6.94 (d, J=8.0, 1H), 6.90 (d, J=3.2, 1H), 6.78 (d, J=3.7, 1H), 4.90 (s, 2H).
22% A solution of isatin (125 mg, 0.85 mmol) in anhydrous dioxane (10 mL) was added dropwise to a solution of sodium hydride (60% dispersion in mineral oil, 24 mg, 0.62 mmol) in anhydrous dioxane (10 mL) at 0 C. under argon. The mixture was allowed to stir for 5 minutes and then <strong>[23784-96-5]2-chloro-5-(chloromethyl)thiophen</strong>e (0.12 mL, 1.02 mmol) in dioxane (10 mL) was added dropwise to the resulting mixture. The reaction mixture was heated at reflux under argon for 16 h and concentrated in vacuo. The crude material was purified by preparative TLC using 1:24 methanol in chloroform as the eluent, giving the desired product as a yellow solid (53 mg, 0.19 mmol, 22%). 1H NMR (400 MHz): δ 7.62 (d, J=7.4, 1H), 7.56 (t, J=7.8, 1H), 7.14 (t, J=7.7, 1H), 6.94 (d, J=8.0, 1H), 6.90 (d, J=3.2, 1H), 6.78 (d, J=3.7, 1H), 4.90 (s, 2H).
In 1,4-dioxane; methanol; chloroform; mineral oil; 1-[(5-CHLORO-2-THIENYL)METHYL]-2H-INDOLE-2,3-DIONE A solution of isatin (125 mg, 0.85 mmol) in anhydrous dioxane (10 mL) was added dropwise to a solution of sodium hydride (60% dispersion in mineral oil, 24 mg, 0.62 mmol) in anhydrous dioxane (10 mL) at 0 C. under argon. The mixture was allowed to stir for 5 minutes and then <strong>[23784-96-5]2-chloro-5-(chloromethyl)thiophen</strong>e (0.12 mL, 1.02 mmol) in dioxane (10 mL) was added dropwise to the resulting mixture. The reaction mixture was heated at reflux under argon for 16 h and concentrated in vacuo. The crude material was purified preparative TLC using 1:24 methanol in chloroform as the eluent, giving the desired product as a yellow solid (53 mg, 0.19 mmol, 22%). 1H NMR (400 MHz): δ 7.62 (d, J=7.4, 1H), 7.56 (t, J=7.8, 1H), 7.14 (t, J=7.7, 1H), 6.94 (d, J=8.0, 1H) 6.90 (d, J=3.2, 1H), 6.78 (d, J=3.7, 1H), 4.90 (s, 2H).
In 1,4-dioxane; methanol; chloroform; mineral oil; 1-[(5-CHLORO-2-THIENYL)METHYL]-2H-INDOLE-2,3-DIONE: A solution of isatin (125 mg, 0.85 mmol) in anhydrous dioxane (10 mL) was added dropwise to a solution of sodium hydride (60% dispersion in mineral oil, 24 mg, 0.62 mmol) in anhydrous dioxane (10 mL) at 0 C. under argon. The mixture was allowed to stir for 5 minutes and then <strong>[23784-96-5]2-chloro-5-(chloromethyl)thiophen</strong>e (0.12 mL, 1.02 mmol) in dioxane (10 mL) was added dropwise to the resulting mixture. Age reaction mixture was heated at reflux under argon for 16 h and concentrated in vacuo. The crude material was purified preparative TLC using 1:24 methanol in chloroform as the eluent, giving the desired product as a yellow solid (53 mg, 0.19 mmol, 22%). 1H NMR (400 MHz): δ 7.62 (d, J=7.4, 1H), 7.56 (t, J=7.8, 1H), 7.14 (t, J=7.7, 1H), 6.94 (d, J=8.0, 1H), 6.90 (d, J=3.2, 1H), 6.78 (d, J=3.7, 1H), 4.90 (s, 2H).
In 1,4-dioxane; methanol; chloroform; mineral oil; 1-[(5-CHLORO-2-THIENYL)METHYL]-2H-INDOLE-2,3-DIONE: A solution of isatin (125 mg, 0.85 mmol) in anhydrous dioxane (10 mL) was added dropwise to a solution of sodium hydride (60% dispersion in mineral oil, 24 mg, 0.62 mmol) in anhydrous dioxane (10 mL) at 0 C. under argon. The mixture was allowed to stir for 5 minutes and then <strong>[23784-96-5]2-chloro-5-(chloromethyl)thiophen</strong>e (0.12 mL, 1.02 mmol) in dioxane (10 mL) was added dropwise to the resulting mixture. The reaction mixture was heated at reflux under argon for 16 h and concentrated in vacuo. The crude material was purified preparative TLC using 1:24 methanol in chloroform as the eluent, giving the desired product as a yellow solid (53 mg, 0.19 mmol, 22%). 1H NMR (400 MHz): δ 7.62 (d, J=7.4, 1H), 7.56 (t, J=7.8, 1H), 7.14 (t, J=7.7, 1H), 6.94 (d, J=8.0, 1H), 6.90 (d, J=3.2, 1H), 6.78 (d, J=3.7, 1H), 4.90 (s, 2H).
In 1,4-dioxane; methanol; chloroform; mineral oil; 1-[(5-CHLORO-2-THIENYL)METHYL]-2H-INDOLE-2,3-DIONE: A solution of isatin (125 mg, 0.85 mmol) in anhydrous dioxane (10 mL) was added dropwise to a solution of sodium hydride (60% dispersion in mineral oil, 24 mg, 0.62 mmol) in anhydrous dioxane (10 mL) at 0 C. under argon. The mixture was allowed to stir for 5 minutes and then <strong>[23784-96-5]2-chloro-5-(chloromethyl)thiophen</strong>e (0.12 mL, 1.02 mmol) in dioxane (10 mL) was added dropwise to the resulting mixture. The reaction mixture was heated at reflux under argon for 16 h and concentrated in vacuo. The crude material was purified preparative TLC using 1:24 methanol in chloroform as the eluent, giving the desired product as a yellow solid (53 mg, 0.19 mmol, 22%). 1H NMR (400 MHz): δ 7.62 (d, J=7.4, 1H), 7.56 (t, J=7.8, 1H), 7.14 (t, J=7.7, 1H), 6.94 (d, J=8.0, 1H), 6.90 (d, J=3.2, 1H), 6.78 (d, J=3.7, 1H), 4.90 (s, 2H).

  • 29
  • [ 23784-96-5 ]
  • [ 251345-20-7 ]
  • [ 121-44-8 ]
  • [ 251345-07-0 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate; In N-methyl-acetamide; water; ethyl acetate; Petroleum ether; B. 2-Hydroxymethyl-4-[3-(5-chlorothiophen-2-ylmethylsulfanyl)propylsulfanyl]-3-methyl-pyridine 6.9 g (26 mmol) of [4-(3-mercaptopropylsulfanyl)-3-methylpyridin-2-yl]methanol hydrochloride and 4.4 g (26 mmol) of 2-chloro-5-chloromethylthiophene are stirred in 100 ml of dimethylformamide for two hours together with 14 g (132 mmol) of sodium carbonate. The mixture is diluted with 100 ml of water and extracted three times with 30 ml of ethyl acetate. The combined organic phases are dried over magnesium sulfate and concentrated. The residue is chromatographed on silica gel using ethyl acetate/petroleum ether/triethylamine=8/2/0.3. 5.9 g (63%) of the title compound are obtained as a crystalline solid, which is used without further purification.
  • 30
  • [ 23784-96-5 ]
  • [ 222162-24-5 ]
  • 1-((5-chloro-thien-2-yl)methyl)-3-(5-ethoxycarbonyl-furan-2-yl)indazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
350 mg (41%) With potassium tert-butylate; In N,N-dimethyl-formamide; EXAMPLE 17 1-((5-Chloro-2-thienyl)methyl)-3-(5-ethoxycarbonyl-2-furyl)indazole: 600 mg (2.3 mmol) of 3-(5-ethoxycarbonyl-2-furyl)indazole together with 265 mg (2.4 mmol) of potassium tert-butoxide were initially charged in 10 ml of DMF, 430 mg (2.6 mmol) of <strong>[23784-96-5]2-chloro-5-(chloromethyl)thiophen</strong>e in 1 ml of DMF were added dropwise and the mixture was stirred at RT for 2 h. Customary work-up gave 350 mg (41%) of the title compound. m.p.: 124-126 C.
  • 31
  • [ 23784-96-5 ]
  • [ 56708-28-2 ]
  • 2-(4-chlorophenylimino)-3-(5-chloro-2-thenyl)-2,3-dihydro-4H-pyrido[3,2-e]-1,3-thiazin-4-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
In N,N-dimethyl-formamide; EXAMPLE 104 2-(4-Chlorophenylimino)-3-(5-chloro-2-thenyl)-2,3-dihydro-4H-pyrido[3,2-e]-1,3-thiazin-4-one and 2-[N-(4-chlorophenyl)-N-(5-chloro-2-thenyl)amino]-4H-pyrido[3,2-e]-1,3-thiazin-4-one The reaction procedure of Example 11 was followed except that 2.536 g (8.75 mmol) of 2-(4-chloroanilino)-4H-pyrido[3,2-e]-1,3-thiazin-4-one, 154 mg of lithium hydride, 1.462 g of 5-chloro-2-thenyl chloride and 40 ml of DMF were used. The resulting residue was then purified through silica gel column chromatography (eluant: chloroform). As a result, 2.643 of 2-(4-chlorophenylimino)-3-(5-chloro-2-thenyl)-2,3-dihydro-4H-pyrido[3,2-e]-1,3-thiazin-4-one (recrystallized from ethanol) was obtained as a low polarity substance, and 263 mg of 2-[N-(4-chlorophenyl)-N-(5-chloro-2-thenyl)amino]-4H-pyrido[3,2-e]-1,3-thiazin-4-one (recrystallized from a mixture of ethyl acetate and diisopropyl ether) was obtained as a high polarity substance.
  • 32
  • [ 1603-41-4 ]
  • [ 23784-96-5 ]
  • [ 136268-35-4 ]
YieldReaction ConditionsOperation in experiment
In acetonitrile; STR478 3.2 g (0.03 mol) of 2-amino-5-methylpyridine are dissolved in 100 ml of acetonitrile, and 5 g (0.03 mol) of 2-chloro-5-chloromethylthiophene are added. The mixture is stirred for 8 hours at 60 C. and for 18 hours at room temperature. The solid which has formed is filtered off with suction and dried. 1.6 g (20% of theory) of N-(5-chlorothien-2-yl-methyl)-5-methyl-2-iminopyridine hydrochloride of melting point 208 C. are obtained.
  • 33
  • [ 23784-96-5 ]
  • [ 178975-94-5 ]
YieldReaction ConditionsOperation in experiment
With thiourea; In methanol; Step 1. Preparation of S-(5-chloro-2-thienylmethyl)-isothiouronium chloride. <strong>[23784-96-5]2-Chloro-5-(chloromethyl)thiophene</strong> (14.5 g, 87 mmol) and thiourea (6.6 g, 87 mol) were dissolved in methanol (30 mL) and heated to reflux for 16 hours. The reaction was cooled to room temperature and a precipitate formed. Ether (150 mL) was added to complete the precipitation of compound. The crystals were isolated by filtration and washed with ether (100 mL). After drying in vacuo, 19.0 g (90%) of pure S-(5-chloro-2-thienylmethyl)-isothiouronium chloride were obtained: 1 H NMR (CD3 OD) δ=4.83p (s, 2H), 6.87p (d, 1H, J=3.8 Hz), 6.96p (d, 1H, J=3.2 Hz).
  • 34
  • [ 23784-96-5 ]
  • [ 85953-00-0 ]
  • [ 132216-72-9 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In 1,2-dimethoxyethane; water; EXAMPLE 1 Preparation of N-[4-chloro-2-fluoro-5-(5-chloro-2-thenyloxy)phenyl]-1,2-piperidinedicarboximide (Compound No. 1) 0.83 g of N-(4-chloro-2-fluoro-5-hydroxyphenyl)-1,2-piperidinedicarboximide was stirred together with 1.40 g of potassium carbonate, 10 ml of dimethoxyethane and 0.42 g of 5-chloro-2-thenyl chloride at 60 to 65 C. for 5 hours. After letting the reaction mixture stand to cool, water was added thereto to precipitate out crystals, followed by filtering off the crystals and washing them with water to thus obtain crude crystals. The crystals were purified with ether to obtain 0.70 g of the title compound. M.P.=135~137 C.
  • 35
  • [ 96-43-5 ]
  • [ 23784-96-5 ]
YieldReaction ConditionsOperation in experiment
58.6% With hydrogenchloride; formaldehyd; concentrated aqueous hydrochloric acid; 1. Preparation of 5-chloro-2-chloromethyl thiophene In a 250 ml round-bottom flask equipped with a mechanical stirrer and an ice/salt bath, were mixed concentrated aqueous hydrochloric acid (40 ml) and 2-chlorothiophene (40 g, 0.34 mol). This mixture was cooled to 0 C. and a stream of gaseous HCl was introduced under the surface of the mixture. A 40% aqueous solution formaldehyde (40 ml) was added dropwise, and the temperature was maintained at 3-8 C. When the addition was complete, stirring was continued for 20 minutes, while HCl gas was continuously passed through the reaction mixture. The resulting mixture was poured on 120 ml ice/water. An oil was separated and the aqueous solution was extracted with ether (2*100 ml). The combined organic extracts were washed with water (2*100 ml) and were dried over anhydrous potassium carbonate. The solvents were stripped and the residue was distilled in vacuo, to collect 33.1 g, 58.6% yield, of a colorless liquid, with a b.p. of 50-53 C. at 0.35 torr. NMR: (CDCl3) 6.7 (m,2H), 4.6 (5,2H).
 

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