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[ CAS No. 211513-37-0 ] {[proInfo.proName]}

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Chemical Structure| 211513-37-0
Chemical Structure| 211513-37-0
Structure of 211513-37-0 * Storage: {[proInfo.prStorage]}
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Product Details of [ 211513-37-0 ]

CAS No. :211513-37-0 MDL No. :MFCD06407886
Formula : C23H35NO2S Boiling Point : -
Linear Structure Formula :- InChI Key :YZQLWPMZQVHJED-UHFFFAOYSA-N
M.W : 389.59 Pubchem ID :6918540
Synonyms :
RO4607381;JTT-705

Calculated chemistry of [ 211513-37-0 ]

Physicochemical Properties

Num. heavy atoms : 27
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.65
Num. rotatable bonds : 10
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 117.6
TPSA : 71.47 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : Yes
Log Kp (skin permeation) : -3.63 cm/s

Lipophilicity

Log Po/w (iLOGP) : 4.38
Log Po/w (XLOGP3) : 7.11
Log Po/w (WLOGP) : 6.49
Log Po/w (MLOGP) : 4.27
Log Po/w (SILICOS-IT) : 6.12
Consensus Log Po/w : 5.67

Druglikeness

Lipinski : 1.0
Ghose : None
Veber : 0.0
Egan : 1.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -6.24
Solubility : 0.000225 mg/ml ; 0.000000576 mol/l
Class : Poorly soluble
Log S (Ali) : -8.43
Solubility : 0.00000145 mg/ml ; 0.0000000037 mol/l
Class : Poorly soluble
Log S (SILICOS-IT) : -6.9
Solubility : 0.0000487 mg/ml ; 0.000000125 mol/l
Class : Poorly soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 3.0
Synthetic accessibility : 3.53

Safety of [ 211513-37-0 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 211513-37-0 ]

* 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 [ 211513-37-0 ]

[ 211513-37-0 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 79-30-1 ]
  • [ 211513-21-2 ]
  • [ 211513-37-0 ]
YieldReaction ConditionsOperation in experiment
97% With pyridine at 20℃; for 1h;
With pyridine In hexane 26.4 Synthesis of S-[2-[1-(2-ethylbutyl)cyclohexanecarbonylamino]-phenyl]2-methylthiopropionate (formula (I); R=1-(2-ethylbutyl)cyclohexyl, X1, X2, X3, X4=a hydrogen atom, Y=carbonyl, Z=isobutyryl) Step 4) Isobutyryl chloride (15.0 ml) was added dropwise to a chloroform solution (300 ml) containing N-(2-mercaptophenyl)-1-(2-ethylbutyl)cyclohexanecarboxamide (43.72 g) obtained in Example 10 and pyridine (27.7 ml) at room temperature under stirring. The solution was stirred for 1 hour. After concentration, hexane was added and the deposited solid was filtered off. The filtrate was concentrated and the resulting residue was purified by silica gel column chromatography (a developing solvent; hexane:ethyl acetate=15:1) to obtain the desired compound (50.72 g, yield: 95%).
  • 2
  • [ 381209-09-2 ]
  • [ 211513-37-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 38 percent / oxalyl chloride / CH2Cl2 / 1 h / 20 °C 2: pyridine / 100 °C 3: Ph3P; H2O / dioxane / 1 h / 50 °C 4: 97 percent / pyridine / 1 h / 20 °C
  • 3
  • [ 3814-34-4 ]
  • [ 211513-37-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: LDA / tetrahydrofuran / 1.5 h / 20 °C 1.2: tetrahydrofuran / 20 °C 2.1: 38 percent / oxalyl chloride / CH2Cl2 / 1 h / 20 °C 3.1: pyridine / 100 °C 4.1: Ph3P; H2O / dioxane / 1 h / 50 °C 5.1: 97 percent / pyridine / 1 h / 20 °C
  • 4
  • [ 211515-46-7 ]
  • [ 211513-37-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: pyridine / 100 °C 2: Ph3P; H2O / dioxane / 1 h / 50 °C 3: 97 percent / pyridine / 1 h / 20 °C
  • 5
  • [ 211513-15-4 ]
  • [ 211513-37-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: Ph3P; H2O / dioxane / 1 h / 50 °C 2: 97 percent / pyridine / 1 h / 20 °C
  • 6
  • [ 98-89-5 ]
  • [ 211513-37-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: LDA / tetrahydrofuran / 1.5 h / 20 °C 1.2: tetrahydrofuran / 20 °C 2.1: 38 percent / oxalyl chloride / CH2Cl2 / 1 h / 20 °C 3.1: pyridine / 100 °C 4.1: Ph3P; H2O / dioxane / 1 h / 50 °C 5.1: 97 percent / pyridine / 1 h / 20 °C
  • 7
  • [ 97-72-3 ]
  • [ 211513-15-4 ]
  • [ 211513-37-0 ]
YieldReaction ConditionsOperation in experiment
98.2% With hydrogen In toluene at 80℃; for 5h; Autoclave; 6 This example was run in an analogous manner to example 1 but using 1.15 g 4.78% nPdnAl2O3/Al2O3 catalyst (519 μmol Pd, SDC materials). The mixture was hydrogenated under vigorous stirring for 5 hrs at the temperature of 80° C. and 5 bar (0.5 MPa). Work-up according to example 1 afforded 9.86 g of thioester as white crystals (yield 98.2%). HPLC analysis showed a purity of 100 area %.Example 1Synthesis of S-[2-[1-(2-ethylbutyl)cyclohexanecarbonylamino]-phenyl]2-methylthiopropionateA solution of 8.2 g of amidodisulfide (12.9 mmol) in 16.9 g toluene and 6.1 g (38.7 mmol) isobutyric anhydride was transferred together with 552 mg Pd/C (519 μmol Pd, EVONIK E101 N/D 10%) to a 185 mL stainless steel autoclave, which was sealed and 3 times pressurized with 5 bar H2 and released to atmospheric pressure. The autoclave was heated under program control to 80° C., and thereafter charged with 5 bar of H2. The hydrogenation was carried out under vigorous stirring for 18 hrs at the temperature of 80° C. and 5 bar (0.5 MPa). After this time the autoclave was cooled to RT, the pressure released and the reaction mixture filtered. The filtrate was evaporated under 50° C./15 mbar and dissolved in 78 g EtOH. Addition of 22 g d.i. H2O under Ar at RT leads to the precipitation of 9.67 g thioester (yield 96.3%) as white crystals with a melting point of 64.2-64.4° C. The observed amount of 1-(2-ethylbutyl)-N-(2-mercaptophenyl)-cyclohexanecarboxamide was less than 0.5%.
97% With hydrogen In toluene at 80℃; for 18h; autoclave; 3 This example was run in an analogous manner to example 1 but using 26.7 g toluene. After work-up and crystallization, 9.73 g of thioester as white crystals (yield 97%) with 100% HPLC area % purity was isolated. A solution of 8.2 g of amidodisulfide (12.9 mmol) in 16.9 g toluene and 6.1 g (38.7 mmol) isobutyric anhydride was transferred together with 552 mg Pd/C (519 μϖιο Pd, EVONIK E101 N/D 10%) to a 185 mL stainless steel autoclave, which was sealed and 3 times pressurized with 5 bar H2 and releasing to atmospheric pressure. The autoclave was heated under program control to 80 °C, thereafter charged with 5 bar of H2. The hydrogenation was carried out under vigorous stirring for 18 hrs at the temperature of 80 °C and 5 bar (0.5 MPa). After this time the autoclave was cooled to RT, the pressure released and the reaction mixture filtered. The filtrate was evaporated under 50 °C/15 mbar and dissolved in 78 gEtOH. Addition of 22 g d.i. H20 under Ar at RT leads to the precipitation of 9.67 g thioester (yield 96.3%) as white crystals with a melting point of 64.2 - 64.4°C. The observed amount of l-(2-ethylbutyl)-N-(2-mercaptophenyl)-cyclohexanecarboxamide was less than 0.5%.
With triphenylphosphine In toluene at 115℃; for 6h; Industry scale; 12 Example 12Extraction of TPPO with a Multi Stage Centrifugal Extractor (Model Used LX526 from Rousselet & Robatel)In a double jacket vessel 114 kg DTDA (459 mol, 0.54 eq) and 99 kg NMM (979 mol, 1.15 eq) was suspended in 555 kg toluene (640 l). The suspension was heated to 100° C. and the suspension became a clear solution. 197 kg acid chloride (854 mol, 1.0 eq, assay corrected) was added to this solution over a period of 30 minutes at 100° C. The reaction mixture was heated at reflux (115° C.) and then stirred for 6 hours under reflux.The reaction mixture was transferred to another double jacket vessel and rinsed with 43 kg toluene (49 l). The reaction mixture was cooled to RT and extracted with 171 kg water twice. 100 kg solvent was evaporated at 50° C. under reduced pressure. At constant volume 500 kg toluene (434 l) was added to the residue while evaporating solvent.121 kg of TPP (461 mol, 0.54 eq) was dissolved in 282 kg toluene (325 l) followed by the addition of the above amidodisulfide solution in toluene at 25° C. 84 kg isobutyric anhydride (531 mol, 0.62 eq) was added. The reaction mixture was heated to reflux (115° C.) and then stirred for 6 hours under reflux.The reaction mixture was completely evaporated at 50° C. under reduced pressure. To the residue was added 930 kg heptane (1348 l). The solution was warmed to 40° C. and extracted with a mixture of 181 kg MeOH (229 l) and 98 kg water (98 l). The aqueous phase was discarded.The heptane solution (feed 1200 l/h) was extracted at 40° C. with methanol/water (65/35) (feed 800 l/h) via a 6 stage centrifugal extractor at 1800 rpm. The vessel was rinsed with 104 kg heptane (150 l) and the heptane was extracted against methanol/water (65/35) in the extractor under the same conditions.The thioester heptane solution was completely evaporated at 55° C. under reduced pressure. To the oily residue was added 1258 kg EtOH (1593 l) and the suspension was heated at 50° C. until the solution was clear. A 16 filter unit with external heating (50° C.) was charged with three activated charcoal filter modules.The reddish-brown thioester solution in ethanol was filtered at 50° C. through the above filter unit and an additional polishing filter (5 μm) within approx. 2 hours and became yellowish. The vessel and the filters were rinsed with 156 kg EtOH (198 l).The clear solution was cooled to RT and seeded with a suspension of 1 kg thioester (2.6 mol, 0.003 eq) seeding crystals in 17 kg EtOH/water 1:1 (m/m). The seeded solution was stirred until a well mixed suspension was obtained (60 minutes), and then, while stirring, 615 kg water (615 l) was added within 60 minutes at RT. After complete addition the crystallization mixture was stirred for 30 minutes and then cooled to -10° C. (Ti) within 3.5 hours and further stirred for min. 60 minutes at this temperature.The suspension was separated on a centrifuge and the isolated crystals were washed with a mixture of 307 kg EtOH (390 l) and 128 kg water (cooled to -10° C.).The wet crystals (approx. 378 kg) were dried in a spherical dryer at 45° C. under reduced pressure for 11 hours. 298.8 kg thioester (assay 99.5%, 763 mol, yield 89.3%) were obtained.
With dihydrogen peroxide; triphenylphosphine In methanol; n-heptane; water for 5h; Reflux; 11 Example 11: Use of excess TPP in heptane followed by H2O2 oxidationIn a double jacket vessel under argon 13.4 g 2,2Λ-dithio dianiline (54 mmol, 0.54 eq) was suspended in 51 g heptane (75 ml). 11.6 g N-methyl morpholine (115 mmol, 1.15 eq) was added. The dark brown suspension was heated to 1000C and the suspension became a clear solution. 23.7 g CAT-acid chloride (CAT13) (100 mmol, 1.0 eq, Assay: 97.3 (% mass)) was added to this solution over a period of 30 minutes at 1000C. The reaction mixture was heated to 113°C under pressure (max 2 bar) and then stirred for 7h at this temperature. The reaction mixture was cooled to 25°C and extracted twice with each 20 g water. The heptane phase was heated to reflux at normal pressure and azeotroped using a Dean-Stark- trap until the heptane phase was dry. The heptane phase was cooled to room temperature.14.7 g triphenyl phosphine (56 mmmol, 0.56 eq) and 24 g heptane (35 ml) were charged to the above solution in heptane at 25°C. 9.82 g isobutyric anhydride (62 mmol, 0.621 eq) were added and rinsed with 7 g heptane (10 ml). The reaction mixture was heated at reflux (1000C) and then stirred for 5h under reflux. An IPC-sample showed 10.8% TPPO, 0% amidothiophenol, 0% amidodisulfide and 84.3% thioester.The reaction mixture was cooled to 35°C and diluted with 27 g heptane (40 ml) and a mixture of 89 g methanol (112 ml) and 37 g water. 11.3 g of 3% H2O2-solution (10 mmol, 0.10 eq.) were added and the biphasic mixture was stirred for 30 minutes at 35°C. The aqueous phase is separated and the organic phase was extracted 4 times with each a mixture of 89 g methanol (112 ml) and 48 g water (48 ml). The phases were always allowed to separate for 10 minutes. The aqueous phases were discarded. The thioester heptane solution was completely evaporated at 500C under reduced pressure. To the oily residue was added 117 g ethanol (148 ml) and the suspension is heated at 500C until the solution was clear. A lab filter unit with external heating (500C) was charged with an activated charcoal filter pad. The reddish-brown thioester ethanol solution was filtered at 500C through above filter unit within approx. 20 minutes and becomes light brown. The flask and the filter unit wer washed with 16 g ethanol (20 ml). The solution was filtered over a polish filter at 500C into an Erlenmeyer flask. The flask and the filter unit was rinsed with 16 g ethanol (20 ml).The filtered thioester ethanol solution was transferred into the double jacket vessel at 500C. The flask was rinsed with 16 g ethanol (20 ml).The clear solution was cooled to 18-200C and seeded with a suspension of thioester (0.3 mmol, 0.003 eq) seeding crystals in 2.0 g ethanol/water 1 :1 (m/m) (2.3 ml). The suspension was stirred until a well mixed suspension is obtained (60 minutes), subsequently and while stirring water was added with the use of a Dosimat within 60 minutes at 24°C. After complete addition the crystallization mixture was stirred for 30 minutes and then cooled to - 100C (T1) within 3.5h and further stirred for min. 60 minutes at this temperature. The suspension was isolated by filtration on paper and the isolated crystals were washed with a mixture of 36 g ethanol (45 ml) and 15 g water (cooled to -100C). The wet crystals (42.5 g) were dried at 45°C under reduced pressure for 16h until the weight was constant. 34.6 g of thioester (88.9 mmol, yield 88.9%) were obtained.

  • 8
  • [ 79-30-1 ]
  • [ 211513-15-4 ]
  • [ 1381883-98-2 ]
  • [ 211513-37-0 ]
YieldReaction ConditionsOperation in experiment
With hydrogen In toluene at 80℃; for 18h; Autoclave; 10 8.2 g of amidodisulfide (12.9 mmol) in 16.8 g toluene and 4.2 g (38.7 mmol) isobutyryl chloride was transferred together with 552 mg Pd/C (519 μmol Pd, EVONIK E101 N/D 10%) to a 185 mL stainless steel autoclave. The mixture was hydrogenated under vigorous stirring for 18 hrs at the temperature of 80° C. and 5 bar (0.5 MPa). Thereafter the reaction mixture was analyzed with HPLC, showed 70.6% conversion of amidodisulfide and 52% thioester HPLC area %. In addition 2.9 area % of 1-(2-ethylbutyl)-N-(2-mercaptophenyl)-cyclohexanecarboxamide and 14.5 area % of 2-[1-(2-ethyl-butyl)-cyclohexyl]-benzothiazole were formed.
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