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[ CAS No. 40412-06-4 ] {[proInfo.proName]}

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Chemical Structure| 40412-06-4
Chemical Structure| 40412-06-4
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Product Details of [ 40412-06-4 ]

CAS No. :40412-06-4 MDL No. :MFCD05150366
Formula : C13H14O3S2 Boiling Point : -
Linear Structure Formula :- InChI Key :HLPRKWVEMYDPAU-UHFFFAOYSA-N
M.W : 282.38 Pubchem ID :3682034
Synonyms :

Calculated chemistry of [ 40412-06-4 ]

Physicochemical Properties

Num. heavy atoms : 18
Num. arom. heavy atoms : 11
Fraction Csp3 : 0.23
Num. rotatable bonds : 5
Num. H-bond acceptors : 3.0
Num. H-bond donors : 0.0
Molar Refractivity : 72.76
TPSA : 79.99 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.72 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.84
Log Po/w (XLOGP3) : 3.24
Log Po/w (WLOGP) : 4.09
Log Po/w (MLOGP) : 2.65
Log Po/w (SILICOS-IT) : 3.68
Consensus Log Po/w : 3.3

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -3.75
Solubility : 0.0497 mg/ml ; 0.000176 mol/l
Class : Soluble
Log S (Ali) : -4.59
Solubility : 0.00721 mg/ml ; 0.0000255 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -5.04
Solubility : 0.00256 mg/ml ; 0.00000908 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 2.97

Safety of [ 40412-06-4 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 40412-06-4 ]

* 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.

  • Upstream synthesis route of [ 40412-06-4 ]
  • Downstream synthetic route of [ 40412-06-4 ]

[ 40412-06-4 ] Synthesis Path-Upstream   1~4

  • 1
  • [ 5402-55-1 ]
  • [ 98-59-9 ]
  • [ 40412-06-4 ]
YieldReaction ConditionsOperation in experiment
98% at 35℃; Cooling with ice (0.87 mol) of 2-thiopheneethanol and 184 g (0.97 mol) of p-toluenesulfonyl chloride were sequentially added to a 1 L three-necked flask, 98 g (0.97 mol) of triethylamine was dropwise added thereto under ice-water bath, And keep the temperature of the reaction liquid not higher than 20 DEG C, dropping finished, heating to 35 DEG C to continue stirring, respectively 24h, 27h sampling, TLC, until the reaction is complete, stop reaction, filtration, filter cake with appropriate amount of dichloromethane And the methylene chloride layer was dried with anhydrous sodium sulfate for 2 hours. The desiccant was filtered off and the desiccant was washed with a small amount of methylene chloride. The filtrate was decompressed in vacuo and the filtrate was evaporated under reduced pressure. Concentrated to constant weight to be brown oil, weighing 203g, yield 98percent,
96.37% With triethylamine In toluene at 5 - 30℃; for 20.8333 h; EXAMPLE 3
Preparation of 2-Thienylethyl Para-Toluenesulphonate (Formula VII) Using Toluene
400 liters of toluene and 163.2 kg of para-toluene sulfonyl chloride were charged into a clean and dry reactor followed by cooling to about 5° C. 100 kg of thiophene-2-ethanol was added at about 5° C. over about 20 minutes followed by addition of 130 kg of triethylamine over about 8 hours, 50 minutes.
The reaction mixture temperature was raised to about 30° C. followed by stirring for about 12 hours.
The reaction mass was filtered through a Nutsche filter and washed with 2*100 liters of toluene.
The reaction filtrate was transferred into another reactor followed by washing with 5*200 liters of water.
Organic and aqueous layers were separated and the organic layer was distilled completely at about below 70° C. under vacuum to afford 212 kg (yield: 96.37percent) of title compound.
Purity by GC: 95.59percent.
96.5% With triethylamine In dichloromethane at -5 - 20℃; for 2 h; 32.7 g (0.17 mol) of p-toluenesulfonyl chloride,40 ml of dichloromethane into the reaction flask, cooled to -5 ° C,20 g (0.16 mol)2-thiopheneethanol.28.4 g (0.28 mol) of triethylamine was slowly added dropwise and the temperature of the reaction solution was maintained at about 0 ° C.Plus Bi, incubated for 2h after the reaction was warmed to room temperature. 2-thiophene ethanol to be consumed until the raw materials, suction filtration,The solid was washed with a small amount of methylene chloride and the filtrate was washed with 50 ml of saturated sodium bicarbonate and dried over anhydrous sodium sulfate. Filtration, concentration of the filtrate, light brown solid precipitated out,Filtered, washed with a small amount of petroleum ether to white,That isP-toluenesulfonate-2-thiophene ethyl ester42.5 g, yield 96.5percent (HPLC purity 99percent)
95.5% With triethylamine In dichloromethane at 7.5 - 22.5℃; for 5 h; EXAMPLE 10
Preparation of 2-(2-Thiophene)Ethanol Tosylate (Formula VII) Using Dichloromethane
4 liters of dichloromethane was added into a reactor at a temperature of about 30° C., cooled to a temperature of about 7.5° C. to which was then added 1.784 kg of p-toluene sulphonyl chloride followed by 1 kg of thiophene-2-ethanol.
1.302 kg of triethylamine was added to the above reaction mass at a temperature of about 7.5° C. followed by slowly raising the temperature of the reaction mass to 22.5° C. for about 5 hours.
The obtained reaction mass was filtered through a pressure Nutsche filter, washed with methylene chloride (2*1 liter) and the mother liquor was collected and transferred into another reactor.
The organic layer was washed with water (5*2 liters).
The organic layer thus obtained was subjected to distillation at a temperature below 70° C. using hot water circulation.
The obtained residue was then cooled to about 30° C. to afford 2.1 kg (yield: 95.5percent) of title compound.
93.6% With triethylamine In toluene at 45℃; for 4 h; Example 1 0.2. Conversion of (S)-1 ,2,3,4-tetrahydro-5-hvdroxy-N-propyl- naphthalen-2-ammonium hydrobromide (VIII) into hydrochloride salt of rotigotine; 10.2.1. Preparation of 2-(2-Thienyl)ethyl-4-toluene sulfonate; 4-toluenesulfonyl chloride (162 g), toluene (363.3 g) and 2-(2-Thienyl)ethanol (104 g) are combined. Triethylamine (93 g) is added maintaining the temperature lower than 45° C. After 4hrs, the mixture is washed with aqueous phosphoric acid, aqueous sodium hydroxide and then water. The organic phase is distilled off under vacuum. Isopropanol (314 g) and heptanes (365.9 g) are added. The batch is crystallized by cooling and isolated at -15° C. The crystals are filtered and washed with heptanes (175 mL). The crystals are then dried under vacuum at room temperature until a melting point of > 30° C is obtained.Yield ( 214 g): 93.6 percentHPLC analyses confirmed purity >99percent and 100 percent assay in comparison to a reference standard.
93.6% With triethylamine In toluene at 45℃; for 4 h; 4-toluenesulfonyl chloride (162 g), toluene (363.3 g) and 2-(2-Thienyl)ethanol (104 g) are combined. Triethylamine (93 g) is added maintaining the temperature lower than 45° C. After 4 hrs, the mixture is washed with aqueous phosphoric acid, aqueous sodium hydroxide and then water. The organic phase is distilled off under vacuum. Isopropanol (314 g) and heptanes (365.9 g) are added. The batch is crystallized by cooling and isolated at −15° C. The crystals are filtered and washed with heptanes (175 mL). The crystals are then dried under vacuum at room temperature until a melting point of 30° C. is obtained. [0255] Yield (214 g): 93.6percent
90% With silica gel In dichloromethane for 2 h; Reflux The 12.8g (0.1mol) 2- (2- thienyl) ethanol, 1000mL of dichloromethane, 21.0g (0.12mol) of p-toluenesulfonic acid chloride and 10.0g of silica gel into the reaction flask, the reaction was refluxed for 2h, cooled, filtered to remove silica gel.The reaction mixture was washed successively with distilled water, saturated sodium carbonate solution, brine, then the methylene chloride solvent was removed by distillation under reduced pressure, to give 26.0g of p-toluenesulfonic acid Preparation of 2- (2-thienyl) ethyl ester, 90percent yield .

Reference: [1] Patent: CN103467486, 2016, B, . Location in patent: Paragraph 0094-0096
[2] Patent: US2007/225320, 2007, A1, . Location in patent: Page/Page column 5
[3] Patent: CN107056801, 2017, A, . Location in patent: Paragraph 0016
[4] Patent: US2007/225320, 2007, A1, . Location in patent: Page/Page column 7
[5] Patent: WO2011/161255, 2011, A2, . Location in patent: Page/Page column 36
[6] Patent: US2013/102794, 2013, A1, . Location in patent: Paragraph 0254-0255
[7] Patent: CN104177328, 2016, B, . Location in patent: Paragraph 0015; 0016
[8] Angewandte Chemie - International Edition, 2014, vol. 53, # 7, p. 1809 - 1813[9] Angew. Chem., 2014, vol. 126, # 07, p. 1840 - 1844,5
[10] Journal of Heterocyclic Chemistry, 1989, vol. 26, # 3, p. 677 - 686
[11] Journal of Heterocyclic Chemistry, 1985, vol. 22, p. 1527 - 1529
[12] Patent: US4399140, 1983, A,
[13] Patent: WO2010/73124, 2010, A2, . Location in patent: Page/Page column 26
[14] Angewandte Chemie - International Edition, 2012, vol. 51, # 2, p. 528 - 532
[15] Patent: US2011/313176, 2011, A1, . Location in patent: Page/Page column 11
[16] Patent: CN105503902, 2016, A, . Location in patent: Paragraph 0017
[17] Patent: CN105399753, 2016, A, . Location in patent: Paragraph 0017
[18] Patent: CN105601645, 2016, A, . Location in patent: Paragraph 0018
[19] Patent: CN105541862, 2016, A, . Location in patent: Paragraph 0015; 0017
[20] Patent: CN105461735, 2016, A, . Location in patent: Paragraph 0018
[21] Patent: CN108707156, 2018, A, . Location in patent: Paragraph 0006; 0008
  • 2
  • [ 5402-55-1 ]
  • [ 104-15-4 ]
  • [ 40412-06-4 ]
YieldReaction ConditionsOperation in experiment
78% With ferric nitrate In 1,2-dichloro-ethaneReflux 12.8 g (0.1 mol) of 2-thiopheneethanol,20.0 g (0.12 mol) of p-toluenesulfonic acid,20.2 g (0.05 mol) of ferric nitrate,100 ml of 1,2-dichloroethane into the reaction flask,Reflux reaction to 2 - thiophene ethanol consumption is completed,filter,The filtrate was washed three times with water,concentrate,The solvent was distilled off under reduced pressure,2-thiophene ethyl p-toluenesulfonate 22g,Yield 78percent.
Reference: [1] Tetrahedron Asymmetry, 2010, vol. 21, # 17, p. 2136 - 2141
[2] Patent: CN106866617, 2017, A, . Location in patent: Paragraph 0011; 0012
  • 3
  • [ 7732-18-5 ]
  • [ 98-59-9 ]
  • [ 40412-06-4 ]
Reference: [1] Patent: US4822775, 1989, A,
  • 4
  • [ 40412-06-4 ]
  • [ 28783-41-7 ]
Reference: [1] Patent: CN107056801, 2017, A,
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