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[ CAS No. 95211-67-9 ] {[proInfo.proName]}

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Chemical Structure| 95211-67-9
Chemical Structure| 95211-67-9
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Product Details of [ 95211-67-9 ]

CAS No. :95211-67-9 MDL No. :MFCD03786747
Formula : C12H17NO2S Boiling Point : -
Linear Structure Formula :- InChI Key :HRPRBNMOLCLEDL-UHFFFAOYSA-N
M.W : 239.33 Pubchem ID :2793326
Synonyms :

Calculated chemistry of [ 95211-67-9 ]

Physicochemical Properties

Num. heavy atoms : 16
Num. arom. heavy atoms : 5
Fraction Csp3 : 0.58
Num. rotatable bonds : 3
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 67.05
TPSA : 80.56 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) : -5.22 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.74
Log Po/w (XLOGP3) : 3.58
Log Po/w (WLOGP) : 2.95
Log Po/w (MLOGP) : 2.17
Log Po/w (SILICOS-IT) : 3.52
Consensus Log Po/w : 2.99

Druglikeness

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

Water Solubility

Log S (ESOL) : -3.61
Solubility : 0.0584 mg/ml ; 0.000244 mol/l
Class : Soluble
Log S (Ali) : -4.96
Solubility : 0.00264 mg/ml ; 0.000011 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -3.06
Solubility : 0.208 mg/ml ; 0.000869 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 1.0 alert
Brenk : 0.0 alert
Leadlikeness : 2.0
Synthetic accessibility : 3.53

Safety of [ 95211-67-9 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 95211-67-9 ]

* 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 [ 95211-67-9 ]

[ 95211-67-9 ] Synthesis Path-Downstream   1~74

  • 1
  • [ 542-85-8 ]
  • [ 95211-67-9 ]
  • [ 132605-09-5 ]
YieldReaction ConditionsOperation in experiment
69% In ethanol for 6h; Heating;
  • 2
  • [ 368-77-4 ]
  • [ 95211-67-9 ]
  • [ 120354-30-5 ]
YieldReaction ConditionsOperation in experiment
33% With hydrogenchloride In chloroform for 2h;
  • 3
  • [ 95211-67-9 ]
  • [ 103-72-0 ]
  • [ 132605-14-2 ]
YieldReaction ConditionsOperation in experiment
93% In pyridine at 60℃; for 5h; 4.13. Ethyl 4-methyl-2-(3-phenylthioureido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (11) A mixture of 2a (18.0 g, 0.075 mol) and phenyl isothiocyanate(10.6 g, 0.079 mol) were heated in pyridine (120 mL) at 60 °C for 5h.The solvent was removed by evaporation. MeOH was added to theresidue and white solid was generated. The mixture was filtered,and the solid was washed by MeOH to give 11 as a white solid.(26.1 g, 93%). 1H NMR (300 MHz, CDCl3) δ 12.22 (s, 1H), 7.94 (s, 1H),7.47 (t, J 6.0 Hz, 2H), 7.40e7.31 (m, 3H), 4.22e4.06 (m, 2H), 3.29 (t,J 6.7 Hz, 1H), 2.73e2.53 (m, 2H), 1.93e1.70 (m, 3H), 1.68e1.59 (m,1H), 1.26 (t, J 7.1 Hz, 3H), 1.11 (d, J 6.8 Hz, 3H). LC-MS (ESI) m/z375.1 [M H]. 13C NMR (101 MHz, CDCl3) δ 176.24, 166.13, 150.36,136.07, 135.88, 130.01, 127.76, 126.39, 125.74, 112.62, 60.45, 29.93,28.94, 24.35, 21.88, 18.11, 14.03. Purity 98.4%.
53.5% In ethanol for 8h; Heating;
  • 4
  • [ 95211-67-9 ]
  • [ 60100-09-6 ]
  • [ 95211-69-1 ]
YieldReaction ConditionsOperation in experiment
27% Heating;
  • 5
  • [ 95211-67-9 ]
  • [ 100-47-0 ]
  • [ 95211-72-6 ]
YieldReaction ConditionsOperation in experiment
35.5% With hydrogenchloride Ambient temperature;
  • 6
  • [ 95211-67-9 ]
  • [ 556-61-6 ]
  • 4-Methyl-2-(3-methyl-thioureido)-4,5,6,7-tetrahydro-benzo[b]thiophene-3-carboxylic acid ethyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% In ethanol for 16h; Heating;
  • 7
  • [ 463-71-8 ]
  • [ 95211-67-9 ]
  • [ 257610-92-7 ]
YieldReaction ConditionsOperation in experiment
89% With calcium carbonate In dichloromethane; water at 20℃; 4.28. Ethyl 2-isothiocyanato-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (3a) To an ice-cooled suspension of CSCl2 (0.96 g, 8.37 mmol) andCaCO3 (0.84 g, 8.37 mmol) in DCM (5 mL) and H2O (10 mL) wasadded dropwise a solution of 2a (2.00 g, 8.37 mmol) in DCM(10 mL). After stirred at room temperature overnight, the mixturewas concentrated, diluted with Et2O, washed with H2O, brine, anddried over anhydrous Na2SO4. The resulting mixture was purifiedwith silica chromatography (5% EtOAc in hexane) to give 3a as awhite solid (2.09 g, 89%). 1H NMR (300 MHz, CDCl3) δ 4.38 (qd,J 7.1, 1.9 Hz, 2H), 3.47e3.32 (m, 3H), 2.77e2.54 (m, 2H), 1.98e1.75(m, 3H), 1.75e1.61 (m, 2H), 1.43 (t, J 7.1 Hz, 3H), 1.16 (d, J 6.8 Hz,3H).
37% With calcium carbonate In dichloromethane; water at 0℃; for 3h;
With triethylamine In tetrahydrofuran at 0℃; for 1h; Tetrahydrobenzothiophene isothiocyanate intermediates (6) General procedure: Tetrahydrobenzothiophine amino ester intermediates (3, 1.0 eq) were dissolved in THF. Then TEA (1.1 eq) was added at 0 oC. To this thiophosgene (1.1 eq) was added slowly at 0 oC. and the reaction was stirred for 1 h. Then THF containing filtrate was evaporated to obtain the desired products.
  • 8
  • [ 583-60-8 ]
  • [ 105-56-6 ]
  • [ 95211-67-9 ]
YieldReaction ConditionsOperation in experiment
80.9% With morpholine; sulfur In ethanol at 20 - 45℃; for 29h; 6.1. Ethyl 2-amino-4-methyl-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate (9) A mixture of sulfur (1.1 g, 36 mmol), 2-methylcyclohexanone (4.04 g, 36 mmol), ethyl cyanoactetate (4.07 g, 36 mmol) and EtOH (150 mL) were placed in a round bottom flask and warmed to 45 °C and treated dropwise with morpholine (3.1 g, 36 mmol) over 15 min. The mixture was stirred for 5 h at 45 °C and 24 h at room temperature. Unreacted sulfur was removed by filtration, and the filtrate was concentrated under reduced pressure to afford an orange solid. The residue was loaded on a silica gel column packed with silica gel and eluted with 10% ethyl acetate in hexane. The fractions containing the desired product (TLC) were pooled and evaporated to afford 9 (6.97 g, 80.9%) as an orange solid; mp 69.9-71 °C; Rf 0.44 (hexane/EtOAc 3:1); 1H NMR (DMSO-d6): δ 1.08-1.10 (d, 3H, J = 6.6 Hz, 4-CH3), 1.25-1.28 (t, 3H, J = 6.8 Hz, COOCH2CH3), 1.57-1.78 (m, 4H), 2.39-2.43 (m, 2H), 3.15-3.17 (m, 1H), 4.10-4.24 (q, 2H, J = 6.8 Hz, COOCH2CH3), 7.23 (s, 2H, NH2 exch). Titled compound was used directly for next step without further characterization.
43% With morpholine; sulfur In ethanol at 45℃; for 5h;
42% With morpholine; sulfur at 20℃; for 48h; 4.1. Ethyl 2-amino-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (2a) A mixture of 2-methylcyclohexanone (33.6 g, 0.3 mol), ethyl 2-cyanoacetate (33.9 g, 0.3 mol), sulfur (9.6 g, 0.3 mol) and morpholine(26.1 g, 0.3 mol) were stirred at room temperature for 48 h.The mixture was directly purified with silica chromatography (5%EtOAc in hexane) to give a pale yellow solid (30.1 g, 42%). 1H NMR(400 MHz, CDCl3) δ 4.37e4.19 (m, 2H), 3.30e3.19 (m, 1H), 2.52e2.45(m, 2H), 1.94e1.70 (m, 3H), 1.67e1.58 (m, 1H), 1.35 (t, J 7.1 Hz, 3H),1.15 (d, J 6.8 Hz, 3H). LC-MS (ESI) m/z 240.1 [M H].
25% With sulfur; diethylamine In ethanol at 20 - 50℃; for 25h; Ethyl 2-amino-4-methyl-4,5,6,7-tetrahvdrobenzothiophene-3-carboxylate To a solution of 2-methylcyclohexanone [583-60-8] (1 g, 8.83 mmol) in EtOH (4 mL) was added ethyl cyanoacetate [105-56-6] (1.10 g, 9.71 mmol), sulphur [7704-34-9] (0.31 g, 9.71 mmol) and diethylamine [109-89-7] (0.973 g, 13.24 mmol). The reaction mixture was stirred at r.t. for 18 h, followed by heating at 50 °C for 7 h and then left at r.t. overnight. The solvent was removed in vacuo and the residue purified by flash column chromatography on silica (gradient elution with 0 - 10% EtOAc in hexane) to afford the title compound (520 mg, 25%) as a yellow solid. 6H (400 MHz, DMSO -d6) 7.23 (s, 2H), 4.27 - 4.07 (m, 2H), 3.22 - 3.10 (m, 1H), 2.47 - 2.32 (m, 2H), 1.87 - 1.62 (m, 3H), 1.61 - 1.47 (m, 1H), 1.26 (t, J 7.1 Hz, 3H), 1.09 (d, J 6.7 Hz, 3H).
With morpholine; sulfur In ethanol at 50℃;
With morpholine; sulfur In ethanol at 50℃;
With morpholine; sulfur In neat (no solvent) at 75℃; for 1h; General procedure: A mixture of cyclohexanone (0.196 g,2.0 mmol), methyl cyanoacetate (0.198 g, 2.0 mmol),elemental sulfur (0.064 g, 2.0 mmol) and morpholine (0.174g, 2.0 mmol) was heated at 75 °C for 1 h. After nearlycomplete conversion to the corresponding 2-aminothiophene, as was indicated by TLC monitoring, thereaction mixture was cooled to r.t. and the solid residue wasrecrystallized from EtOH to afford methyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (6a). Then asolution of 6a (0.211 g, 1 mmol) in benzonitrile (2 mL) washeated within a flask equipped with an air-filled balloon at200 °C for 24 h in a silicone oil bath. Progress of the reactionwas monitored by TLC. After completion of the reaction, the mixture was cooled to r.t. and the excess of benzonitrile wasremoved under the reduced pressure. The crude product waspurified by column chromatography using n-hexane-EtOAc(8:1) as eluent. The solvent was evaporated under thereduced pressure and the residue was crystallized from nhexane-EtOAc (5:1) to afford the pure product 7a as paleyellow crystals. Yield: 0.188 g, 91%
With morpholine; sulfur In ethanol at 70℃; for 5h; Tetrahydrobenzothiophene amino esters intermediates (3) General procedure: Respective cyclohexanones (2a-2h, 1.0 eq) were dissolved in ethanol. To this solution elemental sulfur (1.1 eq) was added. Then ethyl cyanoacetate (1.1 eq) and morpholine (1.6 eq) were added and the reaction mass was stirred for 5 h at 70 0C. Then ethanol was evaporated to get the crude which was purified over silica gel column chromatography to obtain the desired product 3a-3h respectively.

  • 9
  • [ 404-72-8 ]
  • [ 95211-67-9 ]
  • 2-[3-(3-fluoro-phenyl)-thioureido]-4-methyl-4,5,6,7-tetrahydro-benzo[<i>b</i>]thiophene-3-carboxylic acid ethyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyridine at 50℃;
  • 10
  • [ 3940-84-9 ]
  • [ 95211-67-9 ]
  • [ 845520-93-6 ]
YieldReaction ConditionsOperation in experiment
With trichlorophosphate In 1,2-dichloro-ethane 3-Benzyl-5-methyl-2-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one 3-Benzyl-5-methyl-2-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one 2-Amino-4-methyl-4,5,6,7-tetrahydro-benzo[b]-thiophene-3-carboxylic acid ethyl ester (26.6 mmol, 100 mol-%) and N-benzyl-3,4,5-trimethoxy-benzamide (34.6 mmol, 130 mol-%) were dissolved in dry 1,2-dichloroethane. The reaction mixture was cooled with an ice-salt-bath and POCl3 (1.7 ml, 24.6 mmol, 130 mol-%) was added. The reaction mixture was refluxed for 24 hours. During refluxing POCl3 (340 μl) was added twice. The reaction mixture was poured into ice-water and after neutralization with sodium acetate the product was extracted into dichloromethane. The organic phases combined were washed with sodium bicarbonate sat. (3*50 ml) and dried with MgSO4.
YieldReaction ConditionsOperation in experiment
28% With sulfur; triethylamine In methanol at 20℃; for 5h; 5 Preparation 4. Methyl 2-amino-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3- carboxylate General procedure: A solution of 4-phenylcyclohexanone (CAS: 4894-75-1, 2.00 g, 11.5 mmol), methyl cyanoacetate (CAS: 105-34-0, 1.11 ml, 12.6 mmol), diethylamine (CAS: 109-89-7, 0.59 ml, 5.70 mmol) and sulfur (CAS: 7704-34-9, 121 mg, 3.78 mmol) in methanol (20 ml) was stirred at RT for 5 hours. The reaction was left standing for 16 hours and then the precipitate was collected to afford methyl 2-amino-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate as a white solid mixture (2.00 g, yield 61%).lH NMR (CDCb, 400MHz): d = 7.35 - 7.30 (m, 2H), 7.28 - 7.20 (m, 3H), 5.96 (s, 2H), 3.80 (s, 3H), 3.03 - 2.93 (m, 2H), 2.80 - 2.63 (m, 3H), 2.12 - 2.06 (m, 1H), 1.95 - 1.83 (m, 1H).
3-Benzyl-5-methyl-2-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one The compound 2-amino-4-methyl-4,5,6,7-tetrahydro-benzo[b]thiophene-3-carboxylic acid ethyl ester was prepared starting from 2-methylcyclohexanone, cyanoacetic acid ethyl ester and sulphur using morpholino as a base (Gütschow M., et al. J. Med. Chem. 1999, 42, 5437). Compound No. 683 NMR (CDCl3): 1.35 (d, 3H), 1.78 (m, 1H), 1.91 (m, 4H), 2.79 (m, 2H), 3.59 (s, 6H), 3.92 (s, 3H), 5.24 (d, 2H), 6.48 (s, 2H), 7.01 (m, 2H), 7.30 (m, 3H). MS (TOF, ES+) m/z 477 (M+1)
  • 12
  • [ 95211-67-9 ]
  • [ 851852-82-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: pyridine / 50 °C 2: MeONa / methanol / 20 °C
  • 13
  • [ 95211-67-9 ]
  • [ 851853-12-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: pyridine / 50 °C 2: MeONa / methanol / 20 °C 3: K2CO3 / dimethylformamide / 20 °C
  • 14
  • [ 95211-67-9 ]
  • [3-(3-fluorophenyl)-5-methyl-4-oxo-3,4,5,6,7,8-hexahydrobenzo[4,5]thieno[2,3-d]pyrimidin-2-ylsulfanyl]acetic acid hydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: pyridine / 50 °C 2: MeONa / methanol / 20 °C 3: K2CO3 / dimethylformamide / 20 °C 4: NH2NH2 / ethanol / 20 °C
  • 15
  • [ 95211-67-9 ]
  • [ 257611-23-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: 37 percent / CaCO3 / CH2Cl2; H2O / 3 h / 0 °C 2: 81 percent / CH2Cl2 / 5 h / 20 °C 3: 90 percent / conc. aq. H2SO4 / 72 h / 20 °C 4: 63 percent / 3M aq. NaOH / dioxane / 4 h / Heating 5: 83 percent / yellow HgO / CH2Cl2 / 48 h / 20 °C
  • 16
  • [ 95211-67-9 ]
  • [ 257611-08-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 37 percent / CaCO3 / CH2Cl2; H2O / 3 h / 0 °C 2: 81 percent / CH2Cl2 / 5 h / 20 °C 3: 90 percent / conc. aq. H2SO4 / 72 h / 20 °C
  • 17
  • [ 95211-67-9 ]
  • [ 257611-15-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 37 percent / CaCO3 / CH2Cl2; H2O / 3 h / 0 °C 2: 81 percent / CH2Cl2 / 5 h / 20 °C 3: 90 percent / conc. aq. H2SO4 / 72 h / 20 °C 4: 63 percent / 3M aq. NaOH / dioxane / 4 h / Heating
  • 18
  • [ 95211-67-9 ]
  • [ 257611-00-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 37 percent / CaCO3 / CH2Cl2; H2O / 3 h / 0 °C 2: 81 percent / CH2Cl2 / 5 h / 20 °C
  • 19
  • [ 95211-67-9 ]
  • [ 132605-20-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 81 percent / ethanol / 16 h / Heating 2: 79 percent / HCl / ethanol / 24 h / Heating
  • 20
  • [ 95211-67-9 ]
  • [ 132605-24-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 69 percent / ethanol / 6 h / Heating 2: 36 percent / HCl / ethanol / 24 h / Heating
  • 21
  • [ 95211-67-9 ]
  • [ 132605-29-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 53.5 percent / ethanol / 8 h / Heating 2: 51 percent / HCl / ethanol / 24 h / Heating
Multi-step reaction with 3 steps 1: triethylamine / tetrahydrofuran / 1 h / 0 °C 2: tetrahydrofuran / 2 h / 20 °C 3: sodium hydroxide / ethanol / 2 h / Reflux
  • 23
  • [ 29671-92-9 ]
  • [ 95211-67-9 ]
  • [ 1313013-86-3 ]
YieldReaction ConditionsOperation in experiment
59.7% In dimethylsulfone; at 140℃; for 4h; A mixture of 9 (0.74 g, 3.28 mmol) and <strong>[29671-92-9]chloroformamidine hydrochloride</strong> (1.51 g, 13.12 mmol) in dimethyl sulfone (DMSO2) (4 g) was heated at 140 C for 4 h. The mixture was cooled to room temperature and water (15 mL) was added and ammonium hydroxide was used to neutralize the suspension. The brown solid, obtained by filtration, was washed with water and dried over P2O5 in vacuum. The solid was dissolved in methanol and silica gel was added. A dry silica gel plug was obtained after evaporation of the solvent. The plug was loaded on to a silica gel column and eluted with 5% methanol in chloroform. The fractions containing the desired product (TLC) were pooled and evaporated to afford 10 (0.46 g, 59.7%) as a light yellow solid; mp >300 C; Rf 0.5 (MeOH/CHCl3, 1:6); 1H NMR (DMSO-d6) delta 1.18-1.20 (d, 3H, J = 6.8 Hz, CH3), 1.59-1.61 (m, 1H), 1.71-1.83 (m, 3H), 2.54-2.64 (m, 2H), 3.15-3.18 (m, 1H), 6.39 (s, 2H, 2-NH2 exch), 10.73 (s, 1H, 3-NH exch); Anal. (C11H13N3SO·0.2H2O): C, H, N, S.
  • 24
  • [ 95211-67-9 ]
  • [ 1313013-76-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: palladium 10% on activated carbon; 1,3,5-trimethyl-benzene / Reflux 2.1: hydrogenchloride / 4 h 2.2: pH 8 3.1: N-Bromosuccinimide; dibenzoyl peroxide / benzene / 4 h / Reflux 4.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 80 °C / Inert atmosphere 5.1: sodium hydroxide / methanol; water / 12 h / 60 °C 5.2: 2 h / 0 °C / pH 3
  • 25
  • [ 95211-67-9 ]
  • [ 1313013-78-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: palladium 10% on activated carbon; 1,3,5-trimethyl-benzene / Reflux 2.1: hydrogenchloride / 4 h 2.2: pH 8 3.1: N-Bromosuccinimide; dibenzoyl peroxide / benzene / 4 h / Reflux 4.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 80 °C / Inert atmosphere 5.1: sodium hydroxide / methanol; water / 12 h / 60 °C 5.2: 2 h / 0 °C / pH 3
  • 26
  • [ 95211-67-9 ]
  • [ 1313013-80-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: palladium 10% on activated carbon; 1,3,5-trimethyl-benzene / Reflux 2.1: dimethylsulfone / 48 h / 140 °C 3.1: 2 h / Reflux 4.1: N-Bromosuccinimide; dibenzoyl peroxide / 1,2-dichloro-ethane / 24 h / Reflux 5.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 80 °C / Inert atmosphere 6.1: sodium hydroxide / methanol; water / 12 h / 60 °C 6.2: 2 h / 0 °C / pH 3
  • 27
  • [ 95211-67-9 ]
  • [ 1313013-82-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: palladium 10% on activated carbon; 1,3,5-trimethyl-benzene / Reflux 2.1: dimethylsulfone / 48 h / 140 °C 3.1: 2 h / Reflux 4.1: N-Bromosuccinimide; dibenzoyl peroxide / 1,2-dichloro-ethane / 24 h / Reflux 5.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 80 °C / Inert atmosphere 6.1: sodium hydroxide / methanol; water / 12 h / 60 °C 6.2: 2 h / 0 °C / pH 3
  • 28
  • [ 95211-67-9 ]
  • C28H30N4O6S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: palladium 10% on activated carbon; 1,3,5-trimethyl-benzene / Reflux 2.1: hydrogenchloride / 4 h 2.2: pH 8 3.1: N-Bromosuccinimide; dibenzoyl peroxide / benzene / 4 h / Reflux 4.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 80 °C / Inert atmosphere
  • 29
  • [ 95211-67-9 ]
  • C29H30N4O6S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: palladium 10% on activated carbon; 1,3,5-trimethyl-benzene / Reflux 2.1: hydrogenchloride / 4 h 2.2: pH 8 3.1: N-Bromosuccinimide; dibenzoyl peroxide / benzene / 4 h / Reflux 4.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 80 °C / Inert atmosphere
  • 30
  • [ 95211-67-9 ]
  • [ 1313013-88-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: dimethylsulfone / 4 h / 140 °C 2: 2 h / Reflux
  • 31
  • [ 95211-67-9 ]
  • C32H37N5O7S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: palladium 10% on activated carbon; 1,3,5-trimethyl-benzene / Reflux 2: dimethylsulfone / 48 h / 140 °C 3: 2 h / Reflux 4: N-Bromosuccinimide; dibenzoyl peroxide / 1,2-dichloro-ethane / 24 h / Reflux 5: potassium carbonate / N,N-dimethyl-formamide / 1 h / 80 °C / Inert atmosphere
  • 32
  • [ 95211-67-9 ]
  • C33H37N5O7S [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: palladium 10% on activated carbon; 1,3,5-trimethyl-benzene / Reflux 2: dimethylsulfone / 48 h / 140 °C 3: 2 h / Reflux 4: N-Bromosuccinimide; dibenzoyl peroxide / 1,2-dichloro-ethane / 24 h / Reflux 5: potassium carbonate / N,N-dimethyl-formamide / 1 h / 80 °C / Inert atmosphere
  • 33
  • [ 95211-67-9 ]
  • [ 1313013-94-3 ]
YieldReaction ConditionsOperation in experiment
88% With benzonitrile at 200℃; for 24h; General Procedure for the Preparation of Alkyl 2-Aminobenzo[b]thiophene-3-carboxylates 7a-j. General procedure: A mixture of cyclohexanone (0.196 g,2.0 mmol), methyl cyanoacetate (0.198 g, 2.0 mmol),elemental sulfur (0.064 g, 2.0 mmol) and morpholine (0.174g, 2.0 mmol) was heated at 75 °C for 1 h. After nearlycomplete conversion to the corresponding 2-aminothiophene, as was indicated by TLC monitoring, thereaction mixture was cooled to r.t. and the solid residue was recrystallized from EtOH to afford methyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (6a). Then asolution of 6a (0.211 g, 1 mmol) in benzonitrile (2 mL) was heated within a flask equipped with an air-filled balloon at 200 °C for 24 h in a silicone oil bath. Progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was cooled to r.t. and the excess of benzonitrile was removed under the reduced pressure. The crude product was purified by column chromatography using n-hexane-EtOAc(8:1) as eluent. The solvent was evaporated under the reduced pressure and the residue was crystallized from nhexane-EtOAc (5:1) to afford the pure product 7a as paleyellow crystals.
85% With air In benzonitrile at 200℃; for 24h; General Procedure for the Preparation of Alkyl 2-Aminobenzo[b]thiophene-3-carboxylates 7a-j,Exemplified with 7a General procedure: A mixture of cyclohexanone (0.196 g,2.0 mmol), methyl cyanoacetate (0.198 g, 2.0 mmol),elemental sulfur (0.064 g, 2.0 mmol) and morpholine (0.174g, 2.0 mmol) was heated at 75 °C for 1 h. After nearlycomplete conversion to the corresponding 2-aminothiophene, as was indicated by TLC monitoring, thereaction mixture was cooled to r.t. and the solid residue wasrecrystallized from EtOH to afford methyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (6a). Then asolution of 6a (0.211 g, 1 mmol) in benzonitrile (2 mL) washeated within a flask equipped with an air-filled balloon at200 °C for 24 h in a silicone oil bath. Progress of the reactionwas monitored by TLC. After completion of the reaction, the mixture was cooled to r.t. and the excess of benzonitrile wasremoved under the reduced pressure. The crude product waspurified by column chromatography using n-hexane-EtOAc(8:1) as eluent. The solvent was evaporated under thereduced pressure and the residue was crystallized from nhexane-EtOAc (5:1) to afford the pure product 7a as paleyellow crystals. Yield: 0.188 g, 91% (on the basis of 6a
52.1% With palladium 10% on activated carbon; 1,3,5-trimethyl-benzene Reflux; 6.4. Ethyl 2-amino-4-methyl-1-benzothiophene-3-carboxylate (14) A mixture of 9 (0.239 g, 1 mmol), 10% Pd/C (0.239 g) and mesitylene (50 mL) were placed in a round bottom flask and kept at reflux for 1-2 days. The mixture was cooled to room temperature and Pd/C was removed by filtration, and the filtrate was concentrated under reduced pressure to afford a brown oil. The residue was loaded on a silica gel column and eluted with 10% ethyl acetate in hexane. The fractions containing the desired product (TLC) were pooled and evaporated to afford 14 (0.123 g, 52.1%) as an orange semi solid; Rf 0.38 (hexane/EtOAc 3:1); 1H NMR (DMSO-d6): δ 1.29-1.32 (t, 3H, J = 6.8 Hz, COOCH2CH3), 2.38 (s, 3H, CH3), 4.25-4.30 (q, 2H, J = 6.8 Hz,COOCH2CH3), 6.98-7.04 (m, 2H, C6H3), 7.44, 7.45 (d, 1H, J = 4 Hz, C6H3), 7.43 (s, 2H, NH2 exch). Titled compound was used directly for next step without further characterization.
  • 34
  • [ 95211-67-9 ]
  • [ 1313013-90-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: palladium 10% on activated carbon; 1,3,5-trimethyl-benzene / Reflux 2: dimethylsulfone / 48 h / 140 °C
  • 35
  • [ 95211-67-9 ]
  • [ 1313013-92-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: palladium 10% on activated carbon; 1,3,5-trimethyl-benzene / Reflux 2: dimethylsulfone / 48 h / 140 °C 3: 2 h / Reflux
  • 36
  • [ 95211-67-9 ]
  • [ 1313013-96-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: palladium 10% on activated carbon; 1,3,5-trimethyl-benzene / Reflux 2.1: hydrogenchloride / 4 h 2.2: pH 8
  • 37
  • [ 95211-67-9 ]
  • [ 1313014-00-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: palladium 10% on activated carbon; 1,3,5-trimethyl-benzene / Reflux 2.1: hydrogenchloride / 4 h 2.2: pH 8 3.1: N-Bromosuccinimide; dibenzoyl peroxide / benzene / 4 h / Reflux
  • 38
  • [ 95211-67-9 ]
  • [ 1313013-98-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: palladium 10% on activated carbon; 1,3,5-trimethyl-benzene / Reflux 2: dimethylsulfone / 48 h / 140 °C 3: 2 h / Reflux 4: N-Bromosuccinimide; dibenzoyl peroxide / 1,2-dichloro-ethane / 24 h / Reflux
  • 39
  • [ 10544-50-0 ]
  • [ 583-60-8 ]
  • [ 105-56-6 ]
  • [ 95211-67-9 ]
YieldReaction ConditionsOperation in experiment
With 4-methyl-morpholine In neat (no solvent) at 75℃; for 1h; General Procedure for the Preparation of Alkyl 2-Aminobenzo[b]thiophene-3-carboxylates 7a-j. General procedure: A mixture of cyclohexanone (0.196 g,2.0 mmol), methyl cyanoacetate (0.198 g, 2.0 mmol),elemental sulfur (0.064 g, 2.0 mmol) and morpholine (0.174g, 2.0 mmol) was heated at 75 °C for 1 h. After nearlycomplete conversion to the corresponding 2-aminothiophene, as was indicated by TLC monitoring, thereaction mixture was cooled to r.t. and the solid residue was recrystallized from EtOH to afford methyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (6a). Then asolution of 6a (0.211 g, 1 mmol) in benzonitrile (2 mL) was heated within a flask equipped with an air-filled balloon at 200 °C for 24 h in a silicone oil bath. Progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was cooled to r.t. and the excess of benzonitrile was removed under the reduced pressure. The crude product was purified by column chromatography using n-hexane-EtOAc(8:1) as eluent. The solvent was evaporated under the reduced pressure and the residue was crystallized from nhexane-EtOAc (5:1) to afford the pure product 7a as paleyellow crystals.
  • 40
  • [ 95211-67-9 ]
  • 2-hydrazinyl-5-methyl-3-phenyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 130 °C 2: pyridine; hydrazine hydrate / 24 h / 130 °C
Multi-step reaction with 4 steps 1: triethylamine / tetrahydrofuran / 1 h / 0 °C 2: tetrahydrofuran / 2 h / 20 °C 3: sodium hydroxide / ethanol / 2 h / Reflux 4: pyridine; hydrazine hydrate / 24 h / 130 °C
  • 41
  • [ 95211-67-9 ]
  • [ 132605-14-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / tetrahydrofuran / 1 h / 0 °C 2: tetrahydrofuran / 2 h / 20 °C
  • 42
  • [ 95211-67-9 ]
  • [ 103-72-0 ]
  • [ 132605-29-9 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate In N,N-dimethyl-formamide at 130℃; Tetrahydrobenzothienopyrimidines intermediates (4) General procedure: Tetrahydrobenzothiophene amino ester intermediates (3, 1.0 eq) were dissolved in DMF. Then phenyl isothiocyanate or substituted phenyl isothiocyanates (1.5 eq) and K2CO3 (1.5 eq) were added to the reaction mixture. Then the reaction mixture was stirred for 8 - 24 h at 130 oC at reflux conditions. Then the reaction mixture was dissolved in MeOH and neutralized by adding dil. HCl (2 N) slowly. The obtained solid was filtered off and washed with water. This was dried to obtain the desired products.
  • 43
  • [ 95211-67-9 ]
  • ethyl 4-methyl-2-(4-morpholinobenzamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / dichloromethane / 72 h / 20 °C 2: caesium carbonate; chloro(2-dicyclohexylphosphino-2’,6’-diisopropoxy-1,1’-biphenyl)[2-(2’-amino-1,1‘-biphenyl)]palladium(II) 2nd generation / 1,4-dioxane / 75 °C / Inert atmosphere
  • 44
  • [ 95211-67-9 ]
  • 4-methyl-2-[(4-morpholinobenzoyl)amino]-4,5,6,7-tetrahydrobenzothiophene-3-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine / dichloromethane / 72 h / 20 °C 2: caesium carbonate; chloro(2-dicyclohexylphosphino-2’,6’-diisopropoxy-1,1’-biphenyl)[2-(2’-amino-1,1‘-biphenyl)]palladium(II) 2nd generation / 1,4-dioxane / 75 °C / Inert atmosphere 3: lithium hydroxide monohydrate / tetrahydrofuran; methanol / 50 °C
  • 45
  • [ 4837-19-8 ]
  • [ 95211-67-9 ]
  • ethyl 2-(3-(difluoromethoxy)benzamido)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
54% Stage #1: m-(difluoromethoxy)benzoic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 2.5h; Stage #2: (R,S)-ethyl 2-amino-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 20h; 61 Example 61. 2-[[3-(Difluoromethoxy)benzoyl]amino]-4-methyl-4, 5,6,7- tetrahydrobenzothiophene-3-carboxylic acid (Compound 102) To a stirred solution of 3-(difluoromethoxy)benzoic acid (CAS: 4837-19-8, 311 mg, 1.50 mmol) in DCM (10 ml) was added oxalyl chloride (CAS: 79-37-8, 160 m, 1.84 mmol) and DMF (7 pl, 0.08 mmol). The reaction mixture was stirred at RT for 2.5 hours. The reaction was poured to a solution of ethyl 2-amino-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (Preparation 5, Step A, 200 mg, 0.84 mmol) and DIPEA (CAS: 7087-68-5, 0.58 ml, 3.34 mmol). The reaction mixture was stirred at RT for 20 hours. The reaction mixture was partitioned between DCM and a saturated aqueous NaHCCh solution. The two phases were separated and the aqueous phase was extracted with DCM (x3). The combined organic phases were passed through a phase separator and the solvent was removed under reduced pressure. Trituration with MeOH afforded ethyl 2-(3-(difluoromethoxy)benzamido )-4-methyl-4,5, 6, 7 -tetrahydrobenzo[b] thiophene-3 - carboxylate as a yellow solid (223 mg, yield 54%). The title compound was then synthesized according to the procedure described in Example 10 using ethyl 2-(3- (difluoromethoxy)benzamido)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate as a starting material (yellow solid, yield 9%). NMR (DMSO-de, 400MHz): d = 13.07 (br s, 1H), 7.78 (d, J=7.9 Hz, 1H), 7.72 - 7.66 (m, 2H), 7.49 (dd, J=2.2, 8.2 Hz, 1H), 7.38 (t, J=73.6 Hz, 1H), 3.45 - 3.26 (m, 1H, partially obscured by the water peak), 2.75 - 2.56 (m, 2H), 1.88 - 1.64 (m, 4H), 1.18 (d, J=6.7 Hz, 3H), one exchangeable proton not observed. LC/MS (Table 1, Method D) Rt= 3.77 min; MS ra/z: 382 [M+H]+.
  • 46
  • [ 95211-67-9 ]
  • [ 586-75-4 ]
  • ethyl 2-(4-bromobenzamido)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
96% With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 72h; 5 Step B. Ethyl 2-(4-bromobenzamido)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate To a solution of ethyl 2-amino-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (Preparation 5, Step A, 200 mg, 0.84 mmol) in DCM (10 ml) was added DIPEA (CAS: 7087-68- 5, 0.29 ml, 1.67 mmol) and 4-bromobenzoyl chloride (CAS: 586-75-4, 248 mg, 1.13 mmol). The reaction mixture was stirred at RT for 72 hours. The reaction was partitioned between DCM and saturated aqueous NaHCCh solution. The organic phase was separated and passed through a phase separator. The solvent was removed under reduced pressure. Trituration with MeOH gave ethyl 2- (4-bromobenzamido)-4-methyl-4,5,6, 7-tetrahydrobenzo[b]thiophene-3-carboxylate as an off- white solid (338 mg, yield 96%).lH NMR (CDCb, 400MHz): d = 12.44 (s, 1H), 7.88 (d, J=8.3 Hz, 2H), 7.66 (d, J=8.3 Hz, 2H), 4.48 - 4.34 (m, 2H), 3.39 - 3.35 (m, 1H), 2.76 - 2.60 (m, 2H), 1.84 - 1.81 (m, 3H), 1.73 - 1.69 (m, 1H), 1.43 (t, J=7.2 Hz, 3H), 1.20 (d, J=6.8 Hz, 3H).
  • 47
  • [ 95211-67-9 ]
  • [ 4023-34-1 ]
  • [ 612829-73-9 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In dichloromethane for 1.5h; Ethyl 2-(cvclopropanecarbonylamino-4-methyl-4.5.6.7-tetrahvdrobenzothiophene-3-carboxylate Cyclopropanecarbonyl chloride [4023-34-1] (0.22 mL, 2.4 mmol) was added to a solution of intermediate 78 (520 mg, 2.17 mmol) and DIPEA (0.75 mL, 4.3 mmol) in DCM (10 mL). The reaction mixture was stirred for 1.5 h, before diluting with DCM (10 mL) and washing with saturated aqueous sodium hydrogen carbonate solution (2 x 20 mL). The mixture was passed through a phase separator cartridge and the organic phase concentrated in vacuo. The crude product was dissolved into DCM and purified by flash chromatography on silica (gradient elution with 10% - 40% EtOAc in /so-hexane) to afford the title compound (676 mg, 101%) as a cream coloured solid. 6H (300 MHz, DMSO -d6) 11.23 (s, 1H), 4.22-4.41 (m, 2H), 3.24-3.31 (m, 1H), 2.54-2.68 (m, 2H), 1.94-2.03 (m, 1H), 1.58-1.84 (m, 4H), 1.33 (t, 3H, J 7.1 Hz), 1.12 (d, 3H, J 6.8 Hz), 0.84-0.96 (m, 4H).
  • 48
  • [ 95211-67-9 ]
  • 2-(cyclopropanecarbonylamino)-N-(cyclopropylmethyl)-4-methyl-4,5,6,7-tetrahydrobenzothiophene-3-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine / dichloromethane / 1.5 h 2: lithium hydroxide monohydrate; water / 1,4-dioxane / 20 - 70 °C 3: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 72.75 h / 20 °C
  • 49
  • [ 95211-67-9 ]
  • 2-(cyclopropanecarbonylamino)-4-methyl-4,5,6,7-tetrahydrobenzothiophene-3-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / dichloromethane / 1.5 h 2: lithium hydroxide monohydrate; water / 1,4-dioxane / 20 - 70 °C
  • 50
  • [ 95211-67-9 ]
  • 2-amino-N,4-dimethyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide hydrogen chloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: dmap / 1,4-dioxane / 40 °C 2: sodium hydroxide; water / tetrahydrofuran; methanol / 2 h / 80 °C 3: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C 4: hydrogenchloride / 1,4-dioxane / 3 h / 20 °C
  • 51
  • [ 95211-67-9 ]
  • 2-amino-N-benzyl-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide hydrogen chloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: dmap / 1,4-dioxane / 40 °C 2: sodium hydroxide; water / tetrahydrofuran; methanol / 2 h / 80 °C 3: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C 4: hydrogenchloride / 1,4-dioxane / 3 h / 20 °C
  • 52
  • [ 95211-67-9 ]
  • ethyl 2-(3-(4-fluorophenyl)thioureido)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: calcium carbonate / dichloromethane; water / 20 °C 2: pyridine / 3 h / 50 °C
  • 53
  • [ 95211-67-9 ]
  • ethyl 2-(3-(4-methoxyphenyl)thioureido)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: calcium carbonate / dichloromethane; water / 20 °C 2: pyridine / 3 h / 50 °C
  • 54
  • [ 95211-67-9 ]
  • ethyl 4-methyl-2-(3-(4-(trifluoromethoxy)phenyl)thioureido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: calcium carbonate / dichloromethane; water / 20 °C 2: pyridine / 3 h / 50 °C
  • 55
  • [ 95211-67-9 ]
  • ethyl 2-(3-(4-(dimethylamino)phenyl)thioureido)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: calcium carbonate / dichloromethane; water / 20 °C 2: pyridine / 3 h / 50 °C
  • 56
  • [ 95211-67-9 ]
  • ethyl 2-(3-(4-(tert-butyl)phenyl)thioureido)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: calcium carbonate / dichloromethane; water / 20 °C 2: pyridine / 3 h / 50 °C
  • 57
  • [ 95211-67-9 ]
  • ethyl 2-(3-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)thioureido)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: calcium carbonate / dichloromethane; water / 20 °C 2: pyridine / 3 h / 50 °C
  • 58
  • [ 95211-67-9 ]
  • ethyl 2-(3-(3,4-dimethoxyphenyl)thioureido)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: calcium carbonate / dichloromethane; water / 20 °C 2: pyridine / 3 h / 50 °C
  • 59
  • [ 95211-67-9 ]
  • ethyl 4-methyl-2-(3-(4-(trifluoromethyl)phenyl)thioureido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: calcium carbonate / dichloromethane; water / 20 °C 2: pyridine / 3 h / 50 °C
  • 60
  • [ 95211-67-9 ]
  • ethyl 2-(3-(4-aminophenyl)thioureido)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: calcium carbonate / dichloromethane; water / 20 °C 2: pyridine / 3 h / 50 °C
  • 61
  • [ 95211-67-9 ]
  • ethyl 2-(3-(4-hydroxyphenyl)thioureido)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: calcium carbonate / dichloromethane; water / 20 °C 2: pyridine / 3 h / 50 °C
  • 62
  • [ 95211-67-9 ]
  • ethyl 2-(3-(2-hydroxyphenyl)thioureido)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: calcium carbonate / dichloromethane; water / 20 °C 2: pyridine / 3 h / 50 °C
  • 63
  • [ 95211-67-9 ]
  • ethyl 2-(3-(2-fluorophenyl)thioureido)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: calcium carbonate / dichloromethane; water / 20 °C 2: pyridine / 3 h / 50 °C
  • 64
  • [ 95211-67-9 ]
  • ethyl 2-(3-(3-methoxyphenyl)thioureido)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: calcium carbonate / dichloromethane; water / 20 °C 2: pyridine / 3 h / 50 °C
  • 65
  • [ 95211-67-9 ]
  • ethyl 2-(3-benzylthioureido)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: calcium carbonate / dichloromethane; water / 20 °C 2: pyridine / 3 h / 50 °C
  • 66
  • [ 95211-67-9 ]
  • 2-((tert-butoxycarbonyl)amino)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: dmap / 1,4-dioxane / 40 °C 2: sodium hydroxide; water / tetrahydrofuran; methanol / 2 h / 80 °C
  • 67
  • [ 95211-67-9 ]
  • tert-butyl (4-methyl-3-(methylcarbamoyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: dmap / 1,4-dioxane / 40 °C 2: sodium hydroxide; water / tetrahydrofuran; methanol / 2 h / 80 °C 3: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C
  • 68
  • [ 95211-67-9 ]
  • N,4-dimethyl-2-(3-phenylthioureido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: dmap / 1,4-dioxane / 40 °C 2: sodium hydroxide; water / tetrahydrofuran; methanol / 2 h / 80 °C 3: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C 4: hydrogenchloride / 1,4-dioxane / 3 h / 20 °C 5: pyridine / 0.67 h / 60 °C
  • 69
  • [ 95211-67-9 ]
  • tert-butyl (3-(benzylcarbamoyl)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: dmap / 1,4-dioxane / 40 °C 2: sodium hydroxide; water / tetrahydrofuran; methanol / 2 h / 80 °C 3: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C
  • 70
  • [ 95211-67-9 ]
  • N-benzyl-4-methyl-2-(3-phenylthioureido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: dmap / 1,4-dioxane / 40 °C 2: sodium hydroxide; water / tetrahydrofuran; methanol / 2 h / 80 °C 3: HATU; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 20 °C 4: hydrogenchloride / 1,4-dioxane / 3 h / 20 °C 5: pyridine / 0.67 h / 60 °C
  • 71
  • [ 24424-99-5 ]
  • [ 95211-67-9 ]
  • ethyl 2-((tert-butoxycarbonyl)amino)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
93% With dmap In 1,4-dioxane at 40℃; 4.59. Ethyl 2-((tert-butoxycarbonyl)amino)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (5) To a solution of 2a (1.00 g, 4.18 mmol) and DMAP (51 mg,0.42 mmol) in dioxane (15 mL) was added (Boc)2O (1.82 g,8.37 mmol). The mixture was stirred at 40 °C overnight andconcentrated. The residue was purified by silica chromatography(10% EtOAc in hexane) to give a colorless gel (1.32 g, 93%). 1H NMR(300 MHz, CDCl3) δ 4.32e4.13 (m, 2H), 3.45e3.30 (m, 1H),2.78e2.54 (m, 2H), 1.96e1.57 (m, 4H), 1.41 (s, 9H), 1.30 (t, J 7.1 Hz,3H), 1.14 (d, J 6.6 Hz, 3H).
  • 72
  • 2-isothiocyanatopyrazine [ No CAS ]
  • [ 95211-67-9 ]
  • ethyl 4-methyl-2-(3-(pyrazin-2-yl)thioureido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
51% In pyridine at 60℃; for 5h; 4.13. Ethyl 4-methyl-2-(3-phenylthioureido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (11) General procedure: A mixture of 2a (18.0 g, 0.075 mol) and phenyl isothiocyanate(10.6 g, 0.079 mol) were heated in pyridine (120 mL) at 60 °C for 5h.The solvent was removed by evaporation. MeOH was added to theresidue and white solid was generated. The mixture was filtered,and the solid was washed by MeOH to give 11 as a white solid.(26.1 g, 93%).
  • 73
  • [ 95211-67-9 ]
  • [ 532-55-8 ]
  • ethyl 2-(3-benzoylthioureido)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% In pyridine at 60℃; for 5h; 4.13. Ethyl 4-methyl-2-(3-phenylthioureido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (11) General procedure: A mixture of 2a (18.0 g, 0.075 mol) and phenyl isothiocyanate(10.6 g, 0.079 mol) were heated in pyridine (120 mL) at 60 °C for 5h.The solvent was removed by evaporation. MeOH was added to theresidue and white solid was generated. The mixture was filtered,and the solid was washed by MeOH to give 11 as a white solid.(26.1 g, 93%).
  • 74
  • [ 95211-67-9 ]
  • [ 16182-04-0 ]
  • ethyl 2-(3-(ethoxycarbonyl)thioureido)-4-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% In pyridine at 60℃; for 5h; 4.13. Ethyl 4-methyl-2-(3-phenylthioureido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (11) General procedure: A mixture of 2a (18.0 g, 0.075 mol) and phenyl isothiocyanate(10.6 g, 0.079 mol) were heated in pyridine (120 mL) at 60 °C for 5h.The solvent was removed by evaporation. MeOH was added to theresidue and white solid was generated. The mixture was filtered,and the solid was washed by MeOH to give 11 as a white solid.(26.1 g, 93%).
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