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[ CAS No. 100063-22-7 ] {[proInfo.proName]}

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Chemical Structure| 100063-22-7
Chemical Structure| 100063-22-7
Structure of 100063-22-7 * Storage: {[proInfo.prStorage]}
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Product Details of [ 100063-22-7 ]

CAS No. :100063-22-7 MDL No. :MFCD00068161
Formula : C12H11NO2S Boiling Point : -
Linear Structure Formula :- InChI Key :QESSCNMSOLRYBO-UHFFFAOYSA-N
M.W : 233.29 Pubchem ID :700562
Synonyms :

Calculated chemistry of [ 100063-22-7 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 16
Num. arom. heavy atoms : 11
Fraction Csp3 : 0.08
Num. rotatable bonds : 3
Num. H-bond acceptors : 2.0
Num. H-bond donors : 1.0
Molar Refractivity : 65.44
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) : -5.37 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.44
Log Po/w (XLOGP3) : 3.32
Log Po/w (WLOGP) : 2.79
Log Po/w (MLOGP) : 1.91
Log Po/w (SILICOS-IT) : 3.32
Consensus Log Po/w : 2.76

Druglikeness

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

Water Solubility

Log S (ESOL) : -3.69
Solubility : 0.0478 mg/ml ; 0.000205 mol/l
Class : Soluble
Log S (Ali) : -4.69
Solubility : 0.00478 mg/ml ; 0.0000205 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -3.91
Solubility : 0.0288 mg/ml ; 0.000124 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.79

Safety of [ 100063-22-7 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P301+P312-P302+P352-P304+P340-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 100063-22-7 ]

* 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 [ 100063-22-7 ]

[ 100063-22-7 ] Synthesis Path-Downstream   1~94

  • 1
  • [ 1943-83-5 ]
  • [ 100063-22-7 ]
  • [ 126080-13-5 ]
  • 2
  • [ 100063-22-7 ]
  • [ 113387-58-9 ]
YieldReaction ConditionsOperation in experiment
Reference Example 1; Methyl 3-chlorosulfonyl-5-phenyl-2-thiophenecarboxylate; Methyl 3-amino-5-phenyl-2-thiophenecarboxylate (5 g, manufactured by AK Scientific, Inc.) was dissolved in 20% hydrochloric acid (12 ml), and sodium nitrite (1.5 g, manufactured by Wako Pure Chemical Industries, Ltd.) dissolved in water (3.2 ml) under ice cooling was dripped to the resultant solution, and the resultant reaction solution was stirred for 1 hour. An acetic acid solution in which sulfur dioxide (2.5 g) and copper chloride (530 mg, manufactured by KANTO CHEMICAL CO., INC.) were dissolved was slowly added to the solution, and the resultant reaction solution was stirred for 5 hours. The reaction mixture was poured into ice water (100 ml), and a product was extracted with dichloromethane (100 ml), dried with magnesium sulfate and then concentrated to give 6.5 g of the titled compound.
  • 3
  • [ 100063-22-7 ]
  • [ 26118-67-2 ]
  • [ 123420-33-7 ]
  • 4
  • [ 124-42-5 ]
  • [ 100063-22-7 ]
  • [ 156424-47-4 ]
  • 5
  • [ 100063-22-7 ]
  • [ 4755-77-5 ]
  • 3-(ethoxyoxalyl-amino)-5-phenyl-thiophene-2-carboxylic acid methyl ester [ No CAS ]
  • 6
  • [ 100063-22-7 ]
  • 3-chloro-5-phenylthiophene-2-carboxylic acid [ No CAS ]
  • 7
  • [ 75-30-9 ]
  • [ 100063-22-7 ]
  • [ 478028-16-9 ]
  • 8
  • [ 75-44-5 ]
  • [ 100063-22-7 ]
  • [ 478028-43-2 ]
YieldReaction ConditionsOperation in experiment
65% With potassium hydroxide; In water; toluene; Example 119A 6-phenyl-2H-thieno[3,2-d][1,3]oxazine-2,4(1H)-dione Methyl-3-amino-5-phenylthiophene-2-carboxylate (0.25 g, 1.07 mmol) in water (6 mL) was reacted with potassium hydroxide (0.12 g, 2.14 mmol) at 90 C. for 24 hours. The reaction was cooled to 0 C. and phosgene (1.9M in toluene, 0.70 mL, 1.40 mmol) was added dropwise. After stirring at room temperature for 1 hour, the resulting solid was collected by filtration, washed with excess water and dried to give the title compound as a tan solid (0.175 g, 65%).
65% methyl-3-amino-5-phenylthiophene-2-carboxylate (0.25 g, 1.07 mmol) in water (6 ML) was reacted with potassium hydroxide (0.12 g, 2.14 mmol) at 90 C. for 24 hours.The reaction was cooled to 0 C. and phosgene (1.9M in toluene, 0.70 ML, 1.40 mmol) was added dropwise.After stirring at room temperature for 1 hour, the resulting solid was collected by filtration, washed with excess water and dried to give the title compound as a tan solid (0.175 g, 65%).
65% 6-phenyl-2H-thieno [3,2-d][1,3]oxazine-2,4(1H)-dione methyl-3-amino-5-phenylthiophene-2-carboxylate (0.25 g, 1.07 mmol) in water (6 ML) was reacted with potassium hydroxide (0.12 g, 2.14 mmol) at 90 C. for 24 hours.The reaction was cooled to 0 C. and phosgene (1.9M in toluene, 0.70 ML, 1.40 mmol) was added dropwise.After stirring at room temperature for 1 hour, the resulting solid was collected by filtration, washed with excess water and dried to give the title compound as a tan solid (0.175 g, 65%).
  • 9
  • [ 88-49-3 ]
  • [ 100063-22-7 ]
  • 3-(4-chloro-2,5-dimethyl-benzenesulfonylamino)-5-phenyl-thiophene-2-carboxylic acid methyl ester [ No CAS ]
  • 10
  • [ 874-60-2 ]
  • [ 100063-22-7 ]
  • [ 477326-18-4 ]
  • 11
  • [ 100063-22-7 ]
  • [ 99972-47-1 ]
YieldReaction ConditionsOperation in experiment
With potassium hydroxide; In methanol; water; for 3h;Reflux; General procedure: The 5-aryl-3-amino-2-carboxylic acid methyl ester (16.6 mmol) was added to a solution of KOH (60 mL, 0.6 M inH2O) and MeOH (60 mL). The mixture was heated to reflux for 3 h,concentrated, and washed with EtOAc (2 50 mL). The aqueous layer was cooled with ice and acidified by addition of a saturated aqueous solution of KHSO4. The precipitated solid was collected by filtration, washed with H2O (2 30 mL) and dried under reduced pressure over CaCl2.
With potassium hydroxide; In tetrahydrofuran; methanol; water; for 3h;Reflux; General procedure: The 5-Aryl-3-amino-2-carboxylic acid methyl ester (16.6 mmol) was added to a solution of KOH (60 mL, 0.6 M in H2O) and MeOH (60 mL). The mixture was heated to reflux for 3 h, concentrated, and washed with EtOAc (2 x 50 mL). The aqueous layer was cooled with ice and acidified with a saturated aqueous solution of KHSO4.The precipitated solid was collected by filtration, washed with H2O (2 x 30 mL) and dried under reduced pressure over CaCl2.
  • 12
  • [ 100063-22-7 ]
  • [ 74-88-4 ]
  • [ 478028-07-8 ]
  • 14
  • [ 116-11-0 ]
  • [ 100063-22-7 ]
  • [ 478028-16-9 ]
YieldReaction ConditionsOperation in experiment
96% With sodium tris(acetoxy)borohydride; acetic acid; In 1,2-dichloro-ethane; for 2h; To a stirred solution of 3-Amino-5-phenyl-thiophene-2- carboxylic acid methyl ester (1.82 g, 7.8 mmol) in 1, 2- dichloroethane (40 mL) was added sequentially 2- methoxypropene (3.0 mL, 31.2 mmol), ACOH (1.8 mL, 31.2 mmol) and NaBH (OAc) 3 (3.31 g, 15.6 mmol) and stirred for 2 hrs. It was then diluted with EtOAc and H 20. The aqueous solution was adjusted to pH = 7 by adding NAHCO3. The aqueous phase was extracted with EtOAc, the combined extract was washed with brine and dried on MGS04 and filtered. Purification on bond elute with hexane to 5% EtOAc-hexane furnished 3-Isopropylamino-5- phenyl-thiophene-2-carboxylic acid methyl ester (2.07 g, 96% yield NMR (CDC1 3, 400 MHz): 8 7.62 (d, 2H), 7.40 (m, 3H) 6.91 (s, 1H), 3.84 (s, 3H), 3.71 (m, 1H), 1. 35 (d, 6H).
To a solution of S-amino-δ-phenyl-thiophene^-carboxylic acid methyl ester (4.92 g, 21.1 mmol) in DCM (1 10 mL) was added 2-methoxypropene (8.23 mL, 84.4 mmol), acetic acid (4.83 mL, 84.4 mmol) and sodium triacetoxyborohydride (8.94 g, 42.2 mmol) and the mixture <n="38"/>stirred overnight. Ethyl acetate and water were added, the aqueous phase adjusted to pH7 using sodium bicarbonate and then extracted with ethyl acetate. The combined organic extracts were washed with brine and dried over sodium sulphate. The crude product was purified by silica chromatography using a Flashmaster Personal apparatus (Argonaut) eluting with DCM / cyclohexane (1 :4) to give the title compound. MS calcd for (C15H17NO2S+ H)+: 276 MS found (electrospray): (M+H)+ =276
To a solution of S-amino-δ-phenyl-thiophene^-carboxylic acid methyl ester (4.92 g, 21.1 mmol) in DCM (1 10 ml.) was added 2-methoxypropene (8.23 ml_, 84.4 mmol), acetic acid (4.83 ml_, 84.4 mmol) and sodium triacetoxyborohydride (8.94 g, 42.2 mmol) and the mixture stirred overnight. Ethyl acetate and water were added, the aqueous phase adjusted to pH7 using sodium bicarbonate and then extracted with ethyl acetate. The combined organic extracts were washed with brine and dried over sodium sulphate. The crude product was purified by silica chromatography using a Flashmaster Personal apparatus (Argonaut) eluting with DCM / cyclohexane (1 :4) to give the title compound. MS calcd for (Ci5H17NO2S+ H)+: 276 MS found (electrospray): (M+H)+ =276
Intermediate 30 Methyl 3-[(1 -methylethyljaminol-δ-phenyl^-thiophenecarboxylateTo a solution of S-amino-δ-phenyl-thiophene^-carboxylic acid methyl ester (4.92 g, 21.1 mmol) in DCM (1 10 ml.) was added 2-methoxypropene (8.23 ml_, 84.4 mmol), acetic acid (4.83 ml_, 84.4 mmol) and sodium triacetoxyborohydride (8.94 g, 42.2 mmol) and the mixture stirred overnight. Ethyl acetate and water were added, the aqueous phase adjusted to pH7 using sodium bicarbonate and then extracted with ethyl acetate. The combined organic extracts were washed with brine and dried over sodium sulphate. The crude product was <n="46"/>purified by silica chromatography using a Flashmaster Personal apparatus (Argonaut) eluting with DCM / cyclohexane (1 :4) to give the title compound. MS calcd for (C15H17NO2S+ H)+: 276 MS found (electrospray): (M+H)+ =276

  • 15
  • [ 100063-22-7 ]
  • [ 1000409-69-7 ]
YieldReaction ConditionsOperation in experiment
With phenyltrimethylammonium tribromide; calcium carbonate; In methanol; dichloromethane; EXAMPLE 8A methyl 3-amino-4-bromo-5-phenylthiophene-2-carboxylate To a mixture of <strong>[100063-22-7]methyl 3-amino-5-phenylthiophene-2-carboxylate</strong> (2.33 g, 10 mmol) and phenyltrimethylammonium tribromide (9.4 g, 25 mmol) in dichloromethane (25 mL) and methanol (25 mL) was added calcium carbonate (4.03 g, 40 mmol) and the mixture stirred overnight. The solid was filtered off and the filtrate concentrated. The residue was purified by flash chromatography on silica gel using 1:10 ethyl acetate/hexanes to give 2.75 g of the title compound. 1H NMR (DMSO-d6) δ 7.62-7.65 (m, 2H), 7.47-7.51 (m, 3H), 3.80 (s, 3H).
With phenyltrimethylammonium tribromide; calcium carbonate; In methanol; dichloromethane; EXAMPLE 8A methyl 3-amino-4-bromo-5-phenylthiophene-2-carboxylate To a mixture of <strong>[100063-22-7]methyl 3-amino-5-phenylthiophene-2-carboxylate</strong> (2.33 g, 10 mmol) and phenyltrimethylammonium tribromide (9.4 g, 25 mmol) in dichloromethane (25 mL) and methanol (25 mL) was added calcium carbonate (4.03 g, 40 mmol) and the mixture stirred overnight. The solid was filtered off and the filtrate concentrated. The residue was purified by flash chromatography on silica gel using 1:10 ethyl acetate/hexanes to give 2.75 g of the title compound. 1H NMR (DMSO-d6) δ 7.62-7.65 (m, 2H), 7.47-7.51 (m, 3H), 3.80 (s, 3H).
With bromine; acetic acid; at 60℃; for 0.75h; Step 8A: To a solution of methyl-3-amino-5-phenyl thiophene-2-carboxylate (1.0 g, 4.10 mmol) in HOAc (15.0 mL) was added Br2 (0.63 mL, 12.3 mmol). The reaction was heated to 60 C. and allowed to stir approximately 45 minutes, after which it was judged complete by LCMS. The excess Br2 was quenched with excess Na2S2O3, and the crude product was extracted (3*25 mL) into DCM. The combined organic layers were dried over MgSO4 and concentrated in vacuo, affording 1.6 g of crude methyl 3-amino-4-bromo-5-phenylthiophene-2-carboxylate as a light yellow solid >90% purity. 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 3.87 (s, 3 H) 5.74 (br. s, 2 H) 7.41-7.49 (m, 3 H) 7.63-7.68 (m, 2 H); LCMS: m/e=282.1 [M+H]+
  • 16
  • [ 5878-19-3 ]
  • [ 100063-22-7 ]
  • [ 1007171-29-0 ]
YieldReaction ConditionsOperation in experiment
To a solution of methyl S-amino-δ-phenyl^-thiophenecarboxylate (2.0 g; 8.58 mmol) and acetic acid (5 ml.) in dry dichloromethane (100 ml.) was added methoxyacetone (0.91 g; 10.3 mmol) and the reaction mixture stirred at room temperature under nitrogen for 10 minutes. Sodium triacetoxyborohydride (3.6 g; 17.2 mmol) was added in 3 portions and the reaction mixture warmed to reflux under nitrogen for 3 days. A further equivalent sodium triacetoxyborohydride (1.8 g; 8.6 mmol) was added and the reaction mixture stirred to reflux under nitrogen for 2 days. Sodium bicarbonate solution (100 ml.) was added and the mixture stirred for 30 minutes, passed through a hydrophobic frit and evaporated to dryness. The crude product was purified by 120 g silica ISCO chromatography eluted with 0 - 100%EtOAc in cyclohexane to give the title compound.MS calcd for (Ci6H19NO3S + H)+: 306MS found (electrospray): (M+H)+ = 306
Intermediate 31Methyl 3-[1 -methyl-2-(methyloxy)ethyl]amino}-5-phenyl-2-thiophenecarboxylateTo a solution of methyl S-amino-δ-phenyl^-thiophenecarboxylate (2.0 g; 8.58 mmol) and glacial acetic acid (5 ml.) in dry dichloromethane (100 ml.) was added methoxyacetone (0.91 g, 10.3 mmol) and the reaction stirred at room temperature under nitrogen for 10 minutes. Sodium triacetoxyborohydride (3.6 g, 17.2 mmol) was added and the reaction heated at reflux under nitrogen for 3 days. A further addition of sodium triacetoxyborohydride (1.8 g, 8.6 mmol) was added and the reaction heated at reflux under nitrogen for 2 days. After <n="44"/>cooling to room temperature sodium bicarbonate solution (100 ml.) was added and the reaction stirred for 30 minutes, dried using a hydrophobic frit and evaporated to dryness. The crude product was purified by 120 g Si ISCO chromatography eluted EtOAc in cyclohexane (gradient from 0-100%) to give title compound. MS calcd for (Ci6H19NO3S + H)+: 306 MS found (electrospray): (M+H)+ = 306
  • 17
  • [ 2365-48-2 ]
  • [ 33513-42-7 ]
  • [ 98-86-2 ]
  • [ 100063-22-7 ]
  • 18
  • [ 100063-22-7 ]
  • [ 4637-24-5 ]
  • methyl-3-[(1E)-(dimethylamino)methylidene]amino}-5-phenyl-2-thiophenecarboxylate [ No CAS ]
  • 21
  • [ 100063-22-7 ]
  • 4-{2-[1-methyl-4-(1-methyl-4-(1-methyl-4-(3-chloro-5-phenylthiophene-3-carboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido]ethyl}morpholine [ No CAS ]
  • 22
  • [ 100063-22-7 ]
  • 3-(Oxalyl-amino)-5-phenyl-thiophene-2-carboxylic acid [ No CAS ]
  • 23
  • [ 100063-22-7 ]
  • 4-chloro-2-methyl-6-phenyl-thieno[3,2-<i>d</i>]pyrimidine [ No CAS ]
  • 24
  • [ 100063-22-7 ]
  • 2-methyl-6-phenyl-4-piperidylthiopheno[3,2-d]pyrimidine [ No CAS ]
  • 25
  • [ 100063-22-7 ]
  • [ 1026933-67-4 ]
  • 26
  • [ 100063-22-7 ]
  • [ 153628-76-3 ]
  • 27
  • [ 100063-22-7 ]
  • [ 175911-96-3 ]
  • 28
  • [ 100063-22-7 ]
  • [ 153629-26-6 ]
  • 29
  • [ 100063-22-7 ]
  • [ 153629-70-0 ]
  • 30
  • [ 100063-22-7 ]
  • 5-(4-Methyl-piperazin-1-yl)-2-phenyl-pyrrolo[1,2-a]thieno[2,3-e]pyrazine [ No CAS ]
  • 31
  • [ 100063-22-7 ]
  • 5-(4-Benzyl-piperazin-1-yl)-2-phenyl-pyrrolo[1,2-a]thieno[2,3-e]pyrazine [ No CAS ]
  • 32
  • [ 100063-22-7 ]
  • 2-Phenyl-5-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-pyrrolo[1,2-a]thieno[2,3-e]pyrazine [ No CAS ]
  • 33
  • [ 100063-22-7 ]
  • 3-Chloro-5-phenyl-thieno[2,3-d]isothiazole 1,1-dioxide [ No CAS ]
  • 34
  • [ 100063-22-7 ]
  • [ 113387-57-8 ]
  • 37
  • [ 100063-22-7 ]
  • [ 113387-72-7 ]
  • 39
  • [ 100063-22-7 ]
  • [ 119120-84-2 ]
  • 40
  • [ 100063-22-7 ]
  • [ 113412-71-8 ]
  • 41
  • [ 100063-22-7 ]
  • [ 113387-74-9 ]
  • 42
  • [ 91222-04-7 ]
  • [ 100063-22-7 ]
  • [ 710951-20-5 ]
YieldReaction ConditionsOperation in experiment
73% To a stirred solution of methyl-3-amino-5- phenylthiophene-carboxylate (233 mg, 1.0 mmol) and 1- methyl-4-trimethylsilanyloxy-1, 2,3, 6-tetrahydro- pyridine (370 mg, 2.0 mmol) in dichloroethane (3.0 mL) was added AcOH (0.114 mL, 2.0 eq) and followed addition of NaBH (OAc) 3 (424 mg, 2.0 mmol) in one portion. The resultant reaction mixture was stirred at RT for weekend, aq. 10% NAOH (until basic) was added, after 30 min, reaction mixture was extracted with dichloromethane. The organic extract was washed with brine and dried. The crude product was purified on silica gel column using 20% EtOAc/hexane for unreacted starting material followed by CHCL3/MEOH/ET3N (180/16/1) furnished the 3- (l-methyl-piperidin-4- ylamino) -5-phenyl-thiophene-2-carboxylic acid methyl ester (240 mg, 73%). NMR 1H (CDC13, 400 MHz): 7.64-7. 6 (m, 2H), 7.43-7. 34 (m, 3H), 6.83 (brs, 2H), 3.83 (s, 3H), 3.46-3. 4 (m, 1H), 2.82-2. 74 (m, 1H), 2.3 (s, 3H), 2.26-2. 2 (m, 4H), 1.72-1. 62 (m, 2H).
73% TO A STIRRED SOLUTION OF METHYL-3-. AMINO-5- ophene-carboxylate (233 mg, 1.0 mmol) and 1- methyl-4-trimethylsilanyloxy-1, 2, 3, 6-tetrahydro- pyridine (370 mg. 2. 0 CYMOL) IN DICHLOROETHANE (3. 0 mL) was added AcOH (0. l mL, 2.0 eq) and followed addition of NaBH (OAc) 3 (424 MG, 2. G mmol) in one portion. The FESULTANT REACTION MIXTURE WAS stirred at RT for weekend, aq. 10% NaOH (until basic) was added, after 30 min, reaction mixture was extracted with dichloromethane. The organic extract was washed with brine and dried. The crude product was purified on silica gel column using 20% EtOAc/hexane for unreacted starting material followed by CHC13/MEOH/ET3N (180/16/1) furnished the 3- » METHYL-PIPERIDIN-4- ylamino) -5-phenyl-thiophene-2-carboxylic acid methyl ester (240 mg, 73%). NMR 1H (CDC13, 400 MHz): 7.64-7. 6 (m, 2H), 7.43-7. 34 (m, 3H), 6.83 (brs, 2H), 3.83 (s, 3H), 3.46-3. 4 (m, 1H), 2.82-2. 74 (m, 1H), 2.3 (s, 3H), 2.26-2. 2 (m, 4H), 1.72-1. 62 (m, 2H).
  • 43
  • [ 4746-97-8 ]
  • [ 100063-22-7 ]
  • [ 712353-46-3 ]
YieldReaction ConditionsOperation in experiment
77% To a suspension of 3-amino-5-phenyl-thiophene-2- carboxylic acid methyl ester (987 mg, 4.23 mmol) in dry THF (1.0 ml), at room temperature, was added 1,4- cyclohexanedione monoethylene ketal (661 mg, 4.23 mmol), followed by dibutyltin dichloride (129 MG, 0.42 mmol). After 5 min, PHENYL SILANE (575 PL, 4.65 mmol) was added and the reaction mixture was stirred at room temperature for 4 days when a clear solution resulted. It was then concentrated and the residue purified by flash chromatography (0% to 30% EtOAc/Hexane) to obtain 1.22 g (77%) of 3- (1, 4-Dioxa-spiro [4.5] dec-8-ylamino) - 5-phenyl-thiophene-2-carboxylic acid methyl ester. H NMR (CDC13, 400 MHz) 7,64-7, 61 ppm (m, 2H); 7, 42- 7, 33 ppm (m, 3H) ; 6, 85 ppm (s, 1H) ; 3, 96 ppm (s, 4H) ; 3,82 ppm (s, 3H); 3.49 ppm (bs, 1H) ; 2,06-2, 00 ppm (m, 2H); 1,85-1, 81 ppm (m, 2H); 1,79-1, 63 ppm (m, 4H).
  • 44
  • [ 100063-22-7 ]
  • [ 75782-81-9 ]
YieldReaction ConditionsOperation in experiment
95% Step 1A: Methyl 3-amino-5-phenylthiophene-2-carboxylate (468 mg, 2 mmole) was suspended in 16 mL EtOH in a microwave vessel. 2.7 mL of 15% aqueous NaOH (10 mmole) was added and the reaction heated to 100 C. for 30 minutes. Concentrated HCl was added until the reaction mixture was acidic and stirred at room temperature for 30 minutes (CO2 evolution observed). The reaction mixture was partitioned between EtOAc and concentrated aqueous sodium bicarbonate. The aqueous phase was extracted with EtOAc and the combined organics washed with water, brine and dried (MgSO4). Filtration and evaporation gave 332 mg of 3-amino-5-phenylthiophene (95%) as a pale yellow solid. 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 6.14 (d, J=1.65 Hz, 3 H) 6.89 (d, J=1.65 Hz, 1 H) 7.23-7.29 (m, 1 H) 7.32-7.38 (m, 2 H) 7.53-7.57 (m, 2 H).
With 1-methyl-piperazine; 1-methyl-pyrrolidin-2-one; at 160℃; for 4h; Reference Example 3 5-Phenyl-3-thienylamine A mixture of METHYL 3-AMINO-5-PHENYLTHIOPHENE-2-CARBOXYLATE (2.50 g, 10.7 MMOL), 3.5 mL of N-methylpiperazine and 12 mL of N-METHYLPYRROLIDINONE is heated at 160C for 4 hours. The reaction mixture is cooled to room temperature and poured into 100 mL of water. The solids are collected by filtration washing with 50 mL of water. Ethyl acetate and hexane are added and the filtrate is decanted off from the gummy black residue. The filtrate is concentrated to provide 850 mg of 5-PHENYL- 3-thienylamine as a yellow solid, mp 76-78C ; 1 H NMR (DMSO-D6) 84. 87 (s, 2H), 5.98 (d, J = 1.5 Hz, 1 H), 6.95 (d, J = 1.5 Hz, 1 H), 7.28 (m, 1 H), 7.37 (t, J = 7 Hz, 2H), 7.53 (d, J = 7 Hz, 2H); MS 176.2 (M+H) +. Analysis for C8H3CIN2S : Calcd : C, 68.53 ; H, 5.18 ; N, 7.99 Found: C, 68.73 ; H, 4.79 ; N, 7.86.
  • 45
  • [ 100063-22-7 ]
  • [ 201478-72-0 ]
  • [ 712353-22-5 ]
YieldReaction ConditionsOperation in experiment
51% A suspension of 3-amino-5-phenyl-thiophene-2-carboxylic acid methyl ester (0.268 g, 1.15 mmol) and 3-formyl N- Cbz-piperidine (0.284 g, 1.15 mmol) in THF (0.5 mL) was treated with dibutyltin dichloride (17 mg, 0.057 mmol). After 5 min, phenylsilane (156 OL, 1.26 mmol) was added and the mixture was stirred for 6 days at room temperature. The solvent was then evaporated and the residue was purified by silica gel column chromatography using CH2CL2 : hexanes: EtOAc as eluent to provide 3- [ (l-Methyl-piperidin-3-ylmethyl)-amino]-5- phenyl-thiophene-2-carboxylic acid methyl ester as an oil (0.2723 g, 51% YIELD). 1H NMR (CDC13, 400 MHz): 7.63-7. 59 (m, 2H), 7.40-7. 28 (m, 9H), 7.18-6. 84 (br s, 1H), 5.20 (d, 1H), 5.10 (d, 1H), 4.55 (m, 1H), 4.15 (m, 1H), 3.82 (s, 3H), 3.58-3. 40 (m, 2H), 2.90 (t, 1H), 1.88-1. 40 (m, 6H).
  • 46
  • [ 19099-93-5 ]
  • [ 100063-22-7 ]
  • [ 712353-51-0 ]
YieldReaction ConditionsOperation in experiment
96% With phenylsilane;dibutyltin chloride; In tetrahydrofuran; at 20℃; for 48h; To a stirred solution of 3-Amino-5-phenyl-thiophene-2- carboxylic acid methyl ester (1.0 g, 4.29 mmol) in THF (1.0 ml) was added the ketone (1.0 g, 4.29 mmol), dibutyltin dichloride (130 mg, 0.43 mmol) and phenylsilane (582 ul, 4.72 mmol) and the reaction mixture was stirred at room temperature for 2 days. The reaction was then quenched with a saturated NAHC03 solution, and the mixture was extracted 3 times with EtOAc. The combined extracts were then washed with brine and dried on NAZS04, filtered and concentrated. The crude product was purified by flash chromatography (0% to 30% ETOAC/HEX) to give 1.86 g (96%) of 4- (2- Methoxycarbonyl-5-phenyl-thiophen-3-ylamino)- PIPERIDINE-1-CARBOXYLIC acid benzyl ester.
94% To a solution of 3-amino-5-phenyl-thiophene-2-carboxylic acid methyl ester (2.33 g, 10 mmol) in THF (2.0 mL) was added benzyl 4-oxopiperidine-1-carboxylate (2.33 g, 10 mmol), dibutyltin chloride (302 mg, 1.0 mmol) and phenylsilane (1.36 ml, 11 mmol) at room temperature. The reaction mixture was stirred for two days at room temperature and quenched with saturated NaHCO3 aqueous solution. The mixture was extracted with ethyl acetate and washed with brine. Dried and concentrated, the crude was purified on silica gel column to give the title compound (4.23 g, 94%). MS: (ESI) m/z (M+H) 452.16
  • 47
  • [ 712353-75-8 ]
  • [ 100063-22-7 ]
  • [ 712353-76-9 ]
YieldReaction ConditionsOperation in experiment
49% A suspension of methyl 3-amino, 5-phenylthiophene 2- carboxylate (459mg, 1.96mmol) and 1- (4-Methoxy-benzyl)- piperidine-2,4-dione (457mg, 1. 96MMOL) at 21, under N2, was treated with dibutyltin dichloride (29mg, 0.098mmol, 5mol%) followed after 5min with phenylsilane (266DOL, 233mg, 2.15mmol, L. leq). The HETEROGENOUS mixture was stirred for 18h at 21 when a clear solution resulted. The reaction was left a further 5H, then evaporated to a thick oil (1.27g). The crude material was purified over silica using (Hexanes : CH2CL2 : EtOAc = 1: 1 : 1) as eluent to deliver 3- [1- (4-METHOXY-BENZYL)-2-OXO-PIPERIDIN-4-YLAMINO]-5- (1- methyl-hexa-1, 3,5-trienyl)-thiophene-2-carboxylic acid methyl ester as a yellow foam (432mg, 49%) (300MHz, CDCl3) 1.8-1.9(m, 1H), 2.25-2. 44 (m, 1H), 2.95 (dd, J = 1. 5Hz, J = 3. 9OHZ, 1H), 3.98 (dd, J = 1. 5Hz, J = 3. 9OHZ, 1H), 3.22-3. 40 (m, 4H), 3.80 (s, 3H), 3.33 (s, 3H), 3.85- 3.93 (m, 1H), 4.08 (m, 2H), 6.81 (s, 1H), 6.85-6. 9 (m, 2H), 7.20-7. 24 (m, 2H), 7. 36-7. 42 (m, 3H), 7.59-7. 61 (m, 2H).
  • 48
  • [ 5900-58-3 ]
  • [ 124-09-4 ]
  • [ 5162-44-7 ]
  • [ 446-48-0 ]
  • [ 7209-38-3 ]
  • [ 74-96-4 ]
  • [ 4784-77-4 ]
  • [ 22288-78-4 ]
  • [ 542-69-8 ]
  • bromomethyl resin [ No CAS ]
  • 9-fluorenyl-methoxycarbonyl-cyclohexyl alanine [ No CAS ]
  • [ 462-94-2 ]
  • [ 1458-98-6 ]
  • [ 78-77-3 ]
  • [ 1809-10-5 ]
  • [ 110-53-2 ]
  • [ 592-55-2 ]
  • [ 7328-91-8 ]
  • [ 871-76-1 ]
  • [ 105-83-9 ]
  • [ 144-48-9 ]
  • [ 929-59-9 ]
  • [ 107-59-5 ]
  • [ 5324-30-1 ]
  • [ 5428-54-6 ]
  • [ 27129-86-8 ]
  • [ 2417-72-3 ]
  • [ 2581-34-2 ]
  • [ 554-84-7 ]
  • [ 3385-21-5 ]
  • [ 126-38-5 ]
  • [ 636-93-1 ]
  • [ 88-30-2 ]
  • [ 620-13-3 ]
  • [ 823-78-9 ]
  • [ 5035-82-5 ]
  • [ 29022-11-5 ]
  • [ 539-48-0 ]
  • [ 35661-39-3 ]
  • [ 26759-46-6 ]
  • [ 20439-47-8 ]
  • [ 2615-25-0 ]
  • [ 6393-01-7 ]
  • [ 5372-81-6 ]
  • [ 35661-40-6 ]
  • [ 100-39-0 ]
  • [ 611-17-6 ]
  • [ 23915-07-3 ]
  • [ 71989-23-6 ]
  • [ 35737-15-6 ]
  • [ 2592-95-2 ]
  • [ 18880-00-7 ]
  • [ 88681-68-9 ]
  • [ 100063-22-7 ]
  • [ 75-03-6 ]
  • [ 106-94-5 ]
  • [ 104-81-4 ]
  • [ 589-10-6 ]
  • [ 107-15-3 ]
  • [ 109-76-2 ]
  • [ 110-60-1 ]
  • [ 7051-34-5 ]
  • [ 106-95-6 ]
  • [ 622-95-7 ]
  • [ 589-15-1 ]
  • [ 134-20-3 ]
  • [ 2550-36-9 ]
  • [ 89-92-9 ]
  • [ 456-41-7 ]
  • [ 766-80-3 ]
  • [ 459-46-1 ]
  • [ 874-98-6 ]
  • [ 402-49-3 ]
  • [ 870-63-3 ]
  • [ 85118-01-0 ]
  • [ 22115-41-9 ]
  • [ 3958-57-4 ]
  • [ 100-11-8 ]
  • [ 107-82-4 ]
  • [ 6482-24-2 ]
  • [ 3132-64-7 ]
  • [ 112883-41-7 ]
  • [ 3433-80-5 ]
  • [ 52727-57-8 ]
  • C18H15N2O3PolS [ No CAS ]
  • C20H20N3OPolS [ No CAS ]
  • C23H19N2O2PolS [ No CAS ]
  • C18H23ClN3OPolS [ No CAS ]
  • C22H26N3OPolS [ No CAS ]
  • C22H23N2O5PolS [ No CAS ]
  • C20H26ClN2O3PolS [ No CAS ]
  • C23H22ClN2O3PolS [ No CAS ]
  • C20H21FN3O3PolS [ No CAS ]
  • C22H29N2O3PolS [ No CAS ]
  • C21H28N3O3PolS [ No CAS ]
  • C19H26N3O4PolS2 [ No CAS ]
  • C22H30N3OPolS [ No CAS ]
  • C21H28N3O4PolS [ No CAS ]
  • C26H26N3OPolS [ No CAS ]
  • C23H15ClF3N2O2PolS [ No CAS ]
  • C24H22N3O3PolS [ No CAS ]
  • C23H16ClF2N2O2PolS [ No CAS ]
  • C22H22Br2N3OPolS [ No CAS ]
  • C24H26FN2O5PolS [ No CAS ]
  • C25H22FN2O4PolS [ No CAS ]
  • C26H22N3O4PolS [ No CAS ]
  • C25H25ClN3O3PolS [ No CAS ]
  • C25H18ClF2N2O3PolS [ No CAS ]
  • C29H26N3O3PolS [ No CAS ]
YieldReaction ConditionsOperation in experiment
With piperidine; Carbonyldiimidazole; tin-2-ethylhexanoate dihydrate; potassium tert-butylate; water; N-ethyl-N,N-diisopropylamine; trifluoroacetic acid; diisopropyl-carbodiimide; dibromotriphenylphosphorane; In DMF (N,N-dimethyl-formamide); dichloromethane; N,N-dimethyl acetamide; 1,2-dichloro-ethane;Combinatorial reaction / High throughput screening (HTS); EXAMPLE 1 [0213] This example shows the synthesis of a combinatorial library of thioquinazolinone derivatives. [0214] Step 1a: Preparation of Wang Bromide Resin [0215] 40 tea bags containing 2 g each of Wang resin (80 g, 120 mmol) was taken in a 5 L PP container. A solution of triphenylphosphine dibromide (152 g, 0.15 M, 3 eq., 360 mmol) in 2000 ml DCM was added and the solution was shaken at room temperature overnight. The resin was sequentially washed with DCM (4×, 1.5 L each) and diethylether (6×, 1.5 L each) and dried under vacuum, to give the bromo wang resin. [0216] Step 1b: Loading of the Nitrophenol on Bromo Wang [0217] 20 g of the Bromo wang resin (1.5 meq/g) was taken in a 2 L wide-mouthed glass container and 1000 mL DMA was addded to it followed by the addition of the nitro phenol (10 eq., 0.3M, 300 mmol). Potasium t-butoxide (33.46 g, 10 eq., 300 mmol) was then added to it and the bottles were heated at 50 C. overnight. The bags were washed alternatively with DMF (500 mL) and DCM (500 mL) 3 cycles followed by 6 cycles of MeOH (500 mL). The tea bags were then dried overnight in air. The following nitrophenols were used: [0218] 2-METHYL-5-NITROPHENOL [0219] 5-HYDROXY-2-NITROBENZOTRIFLUORIDE [0220] 3-METHYL-4-NITROPHENOL [0221] 2-METHOXY-5-NITROPHENOL [0222] M-NITROPHENOL [0223] Step 1c: Reduction of the Nitro Group to Amine [0224] A 2.0 M solution of tin-2-ethylhexanoate dihydrate was prepared in DMF containing 0.5% H2O. The tea bags were added and the solution is heated at 50 C. for 40 hours. After cooling the bags are washed with DMF/10% HOAc (3×), DMF (3×), 5% DIEA/DCM (2×), DCM (2×) and MeOH (2×) and dried in air overnight. [0225] Step 1d: Coupling N-FMOC Protected Amino Acid to Wang Resin. [0226] 20 g of Wang resin (1.5 meq/g) was placed in a porous polypropylene packet (Tea-bag, 60 mm×60 mm, 65mu) and taken in a 1000 mL plastic bottle. DMF (300 mL), DCM (300 mL), FMOC-Cyclohexyl alanine (70.82 g, 6 eq., 0.3M, 180 mmol), DIC (22.71 g, 6 eq., 180 mmol), HOBt (24.32 g, 6 eq., 180 mmol) were added sequentially. After shaking for 12 hours, the packet was washed alternatively with DMF (500 mL) and DCM (500 mL) 3 cycles followed by 6 cycles of MeOH (500 mL). The packet was then dried overnight in air. The tea bags containing the amino acids were then treated with 20% piperidine/DMF for 2 h at room temperature to deblock the FMOC group. The following amino acids were used: [0227] FMOC-GLY-OH [0228] FMOC-ALA-OH [0229] FMOC-L-ISOLEUCINE [0230] FMOC-L-PHENYLALANINE [0231] FMOC-D-NLE-OH [0232] FMOC-CHA-OH [0233] FMOC-L-TRYPTOPHAN [0234] Step 1e: Coupling of the Diamines to Wang Resin [0235] 20 g of Wang resin (1.5 meq/g) was placed in a porous polypropylene packet (Tea-bag, 60 mm×60 mm, 65mu) and taken in a 1000 mL Nalgene bottle. 600 mL of DCM was added followed by the addition of the carbonyl diimidazole (29.9 g, 6 eq., 0.3M, 180 mmol) and the flasks were shaken at room temperature for 3 hours after which they were decanted and washed with DCM (2×, 600 mL). To these Nalgene bottles were added the diamines (6 eq., 0.4M, 180 mmol) in 450 mL of DCM (0.4M) and they were shaken at room temperature overnight. The diamines used were as follows: [0236] 2,2-DIMETHYL-1,3-PROPANEDIAMINE [0237] 1,3-CYCLOHEXANEDIAMINE [0238] (1R,2R)-(-)-1,2-DIAMINOCYCLOHEXANE [0239] TRANS-1,4-DIAMINOCYCLOHEXANE [0240] P-XYLYLENEDIAMINE [0241] 1,4-BIS(3-AMINOPROPYL)PIPERAZINE [0242] ETHYLENEDIAMINE [0243] 1,3-DIAMINOPROPANE [0244] 1,8-DIAMINO-3,6-DIOXAOCTANE [0245] 1,4-DIAMINOBUTANE [0246] 1,5-DIAMINOPENTANE [0247] 1,6-HEXANEDIAMINE [0248] N,N-BIS(3-AMINOPROPYL)METHYLAMINE [0249] 2,2'-THIOBIS(ETHYLAMINE) [0250] 2,5-DIMETHYL-1,4-PHENYLENEDIAMINE [0251] After shaking overnight, the packets was washed alternatively with DMF (500 mL) and DCM (500 mL) 3 cycles followed by 6 cycles of MeOH (500 mL). The packet was then dried in air. [0252] Step 2: Formation of the Isothiocyanate [0253] The o-amino benzoate ester (136 g, 10 eq., 900 mmol) was taken in a 5 L wide-mouthed glass bottle and 2.7 L of dichloroethane was added to it (0.3M). The following esters were used: [0254] METHYL ANTHRANILATE [0255] METHYL 2-AMINO-4-CHLOROBENZOATE [0256] 2-AMINO-4,5-DIMETHOXYBENZOIC ACID [0257] METHYL ESTER [0258] METHYL 3,4,5-TRIMETHOXYANTHRANILATE [0259] DIMETHYL AMINOTEREPHTHALATE [0260] METHYL 2-AMINO-5-BROMOBENZOATE [0261] METHYL 3-AMINOTHIOPHENE-2-CARBOXYLATE [0262] METHYL 3-AMINO-5-PHENYLTHIOPHENE-2-CARBOXYLATE [0263] Thiocarbonyl diimidazole (160 g, 10 eq., 900 mmol) was added to it and the solution was heated at 55 C. overnight to form the isothiocyanate. [0264] Step 3: Formation of the Thioquinazolinone [0265] The next day the tea bags containing the amino acids, diamines and the amino phenols on wang resin (90 mmol) was added to the isothiocyanate solution from reaction 2 and the glass bottles were heated at 55 C. overnight. After cooling the bags was washed alternatively with DMF (2000 mL) and DCM (2000 mL) 3 cycles followed by 6 cycles of MeOH...
  • 49
  • [ 100063-22-7 ]
  • [ 3019-71-4 ]
  • methyl 5-phenyl-3-([(trichloroacetyl)amino]carbonyl}amino)thiophene-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
99% In tetrahydrofuran; for 1.25h; Example 175; 5-Phenvl-3-ureido-thiophene-2-carboxvlic acid (S)-azepan-3-ylamide methvl 5-phenvl-3- (f (trichloroacetvl) aminol carbonvlamino) thiophene-2-carboxylate. ; To a stirred solution of <strong>[100063-22-7]methyl 3-amino-5-phenylthiophene-2-carboxylate</strong> (1.9 g, 8.0 mmol) in anhydrous THF (16 mL) was added trichloroacetyl isocyanate (0.95 mL, 8.0 mmol) slowly over a period of 15 min. After the addition was complete, a precipitate formed and the reaction stirred for an additional lh. The desired product was obtained by filtration to give the title compound (99%) as white solid. The product was used in the next step without any further purification. LC/MS (ES, M+H=421).
  • 50
  • [ 100063-22-7 ]
  • methyl 3-acetamido-5-phenylthiophene-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Methyl 3-Acetamido-5-phenylthiophene-2-carboxylate Methyl 3-amino-5-phenylthiophene-2-carboxylate (2.5031 g, 10.73 mmol) was acetylated as described above and purified by EtOH recrystallization to afford pure product as white crystals (2.7726 g, 10.07 mmol, 93.8%); mp: 115 C.; TLC: Rf=0.70 (Solvent I), 0.70 (Solvent J); IR (cm-1): 3319 (NH), 3122 (CH), 2950 (CH), 1715 (ester C=O), 1680 (amide C=O), 765 (=CH); 1H nmr (CDCl3): δ 10.18 (br s, 1H), 8.38 (s, 1H), 7.66 (m, 2H), 7.41 (m, 3H), 3.90 (s, 3H), 2.25 (s, 3H).
  • 51
  • [ 109-01-3 ]
  • [ 100063-22-7 ]
  • [ 75782-81-9 ]
YieldReaction ConditionsOperation in experiment
With 1-methyl-pyrrolidin-2-one; In hexane; water; ethyl acetate; REFERENCE EXAMPLE 3 5-Phenyl-3-thienylamine A mixture of <strong>[100063-22-7]methyl 3-amino-5-phenylthiophene-2-carboxylate</strong> (2.50 g, 10.7 mmol), 3.5 mL of N-methylpiperazine and 12 mL of N-methylpyrrolidinone is heated at 160 C. for 4 hours. The reaction mixture is cooled to room temperature and poured into 100 mL of water. The solids are collected by filtration washing with 50 mL of water. Ethyl acetate and hexane are added and the filtrate is decanted off from the gummy black residue. The filtrate is concentrated to provide 850 mg of 5-phenyl-3-thienylamine as a yellow solid, mp 76-78 C.; 1H NMR (DMSO-d6) δ 4.87 (s, 2H), 5.98 (d, J=1.5 Hz, 1H), 6.95 (d, J=1.5 Hz, 1H), 7.28 (m, 1H), 7.37 (t, J=7 Hz, 2H), 7.53 (d, J=7 Hz, 2H); MS 176.2 (M+H)+. Analysis for C8H3ClN2S: Calcd: C, 68.53; H, 5.18; N, 7.99 Found: C, 68.73; H, 4.79; N, 7.86.
  • 52
  • [ 100063-22-7 ]
  • 6-chloro-7-methyl-3-methylthio-1,4,2-benzodithiazin 1,1-dioxide [ No CAS ]
  • [ 1042360-39-3 ]
  • 53
  • [ 64-18-6 ]
  • [ 100063-22-7 ]
  • [ 209853-24-7 ]
YieldReaction ConditionsOperation in experiment
6-Phenyl-3H-thieno[3, 2-d]pyrimidin-4-one VIIb21.4 g of ammonium acetate are added to a solution of 50 g of methyl 3-amino- 5-phenylthiophene-2-carboxylate IX in 168 ml of formic acid and the mixture is then heated under reflux for 6 hours. After cooling to 25C, the mixture is filtered and the crystals obtained are washed with water and then dried under reduced pressure. 62.3 g of the resulting formate are added to 56.2 ml of formamide and admixed with 45.1 g of ammonium formate. The mixture is stirred at 1400C for 10 hours and cooled to 25C, water is added and the precipitate formed is filtered off with suction. The precipitate is washed with water and dried under reduced pressure. In this way, 37.2 g of compound VIIb are obtained. NMR (300 MHz, DMSO-d6): δ = 7.38-7.52 (3H), 7.78-7.86 (3H), 8.13 (1 H).
6-Phenyl-3H-thieno[3, 2-d]pyrimidin-4-one VIIb21.4 g of ammonium acetate are added to a solution of 50 g of methyl 3-amino- 5-phenylthiophene-2-carboxylate IX in 168 ml of formic acid and the mixture is then heated under reflux for 6 hours. After cooling to 25C, the mixture is filtered and the crystals obtained are washed with water and then dried under reduced pressure. 62.3 g of the resulting formate are added to 56.2 ml of formamide and admixed with 45.1 g of ammonium formate. The mixture is stirred at 1400C for 10 hours and cooled to 25C, water is added and the precipitate formed is filtered off with suction. The precipitate is washed with water and dried under reduced pressure. In this way, 37.2 g of compound VIIb are obtained. NMR (300 MHz, DMSO-d6): δ = 7.38-7.52 (3H), 7.78-7.86 (3H), 8.13 (1 H)
  • 54
  • [ 100063-22-7 ]
  • [ 75-36-5 ]
  • [ 330662-26-5 ]
YieldReaction ConditionsOperation in experiment
83% A solution of the ester 44a (1 Og, 4 3 mmol) in 1 0 M NaOH (8 5 ml_, 8 5 mmol) THF (8 6 mL) and MeOH (8 6 mL) is stirred at RT for 72 h and then at reflux for 3 h The volatile solvents are reduced under pressure and 10% HCI (25 mL) is added The white solid is collected by filtration, suspended in iso-propanol (9 1 mL) and solid oxalic acid (470 mg, 5 2 mmol) is added The suspension is gently warmed to 400C for 1 h, then cooled to RT and diluted with Et2O The resulting precipitate is collected by filtration and air dried The white solid and Et3N (1 8 mL, 13 mmol) are dissolved in DCM (5 mL) and acetyl chloride (0 37 mL, 5 3 mmol) is added very slowly The reaction is stirred for 3 h and then quenched with water (5OmL) The mixture is extracted with EtOAc (2 x 5OmL) and the combined organic layers dried over Na2SO4 and concentrated to provide pure amide 44b (473 mg, 83% yield)
  • 55
  • [ 100063-22-7 ]
  • [ 124-40-3 ]
  • [ 1215310-63-6 ]
YieldReaction ConditionsOperation in experiment
76% Step c:Methyl 3-[(dimethylamino)diazenyl]-5-phenylthiophene-2-carboxylate: To a solution of <strong>[100063-22-7]methyl 3-amino-5-phenylthiophene-2-carboxylate</strong> (5 g, 21.4 mmol) and cone. HCl (9 mL, 85.8 mmol) in H2O (51 mL) was added acetone (30 mL) to dissolve the product. Then NaNO2 (1.7 g, 23.6 mmol) was added in portions for 15 min at O0C. After stirring at 0-50C for 1 h, the reaction mixture was added to the solution Of K2CO3 (11.2 g, 81.5 mmol) and dimethylamine (8.5 mL, 40%, 77.2 mmol) in H2O (60 mL) at O0C. The mixture was stirred at 0-5C for 1 h and poured into ice cold water. The solution was extracted with chloroform (3 x 100 mL). The combined CHCl3 layer was washed with water, brine and dried over sodium sulfate. The solution was filtered and evaporated the solvent. The residue was chromatographed over silica gel column using hexane-EtOAc (90:10) as eluents to give the product as a pale brown color solid (3.8 g, 76%), mp 92-94 0C. 1H NMR (400 MHz, DMSO-d6): δ 7.78-7.80 (2H, m), 7.64 (IH, s), 7.46-7.52 (3H, m), 3.84 (3H, s), 3.60 (3H, s), 3.28 (3H, s); LC-MS (positive ion mode): m/z 290 (M+H)+
76% Step c:; Methyl 3-[(dimethylamino)diazenyl]-5-phenylthiophene-2-carboxylate: To a solution of <strong>[100063-22-7]methyl 3-amino-5-phenylthiophene-2-carboxylate</strong> (5 g, 21.4 mmol) and conc. HCl (9 mL, 85.8 mmol) in H2O (51 mL) was added acetone (30 mL) to dissolve the product. Then NaNO2 (1.7 g, 23.6 mmol) was added in portions for 15 min at 0 C. After stirring at 0-5 C. for 1 h, the reaction mixture was added to the solution of K2CO3 (11.2 g, 81.5 mmol) and dimethylamine (8.5 mL, 40%, 77.2 mmol) in H2O (60 mL) at 0 C. The mixture was stirred at 0-5 C. for 1 h and poured into ice cold water. The solution was extracted with chloroform (3×100 mL). The combined CHCl3 layer was washed with water, brine and dried over sodium sulfate. The solution was filtered and evaporated the solvent. The residue was chromatographed over silica gel column using hexane-EtOAc (90:10) as eluents to give the product as a pale brown color solid (3.8 g, 76%), mp 92-94 C. 1H NMR (400 MHz, DMSO-d6): δ 7.78-7.80 (2H, m), 7.64 (1H, s), 7.46-7.52 (3H, m), 3.84 (3H, s), 3.60 (3H, s), 3.28 (3H, s); LC-MS (positive ion mode): m/z 290 (M+H)+.
  • 56
  • [ 78583-84-3 ]
  • [ 2365-48-2 ]
  • [ 100063-22-7 ]
YieldReaction ConditionsOperation in experiment
69% With sodium methylate; In methanol; for 3h;Reflux; General procedure: An apropriate substrate S2a-n, from the previous step, in dry MeOH (15 ml) [THF (15 ml) was used in the case of 3,4-dirnethoxyphenyl substrate S2m] was added dropwise to a stirred mixture of methyl thioglycolate (3.5 ml, 38 mmol) and NaOMe, prepared by dissolving Na (1.15 g, 50 mmol) in dry MeOH (20 ml), at 0 C during 30 min. The formed suspension was intensely stirred and heated at reflux for 3 h. Then, the reaction mixture was poured in ice cold water (100 ml) and neutralized with AcOH (1.10 ml). The precipitate was filtered, washed with water (5x10 ml), MeOH (10 ml) and dried under air. Esters 1 were purified by crystallization from EtOH, except for compoimd 1l, which was crystallized from Et2O. Yields of esters 1a-n are based on methyl ketones S1a-n. 5-Styryl-substituted derivative 1o was prepared in the same manner by the reaction of substrate S2o (4.55 g, 24 mmol) with methyl thioglycolate (2.75 ml, 30 mmol) in the presence of NaOMe, from Na (0.92 g, 40 mmol), dry MeOH (30 ml). Compound 1o was purified by crystallization from EtOH.
50% Step b:Methyl S-amino-S-phenylthiophene^-carboxylate: To a solution of methyl thioglycolate (1 g, 9.43 mmol) in methanol (5 mL) was added a solution of sodium methoxide (0.5 g, 9.43 mmol) in methanol (5 mL) and stirred for 0.5 h. To the above mixture, a solution of 3-chloro-3-phenylprop-2-enenitrile (1.22 g, 7.5 mmol) in DMF (3.5 mL) was added dropwise for 10 min at rt and stirred the mixture at 6O0C for 2 h. Then, a solution of sodium methoxide (1 g, 18.6 mmol) in methanol (10 mL) was added dropwise at rt and stirring was continued for 2 h at 6O0C. The mixture was allowed to rt and poured into cold water and stirred for 15 min. The solution was extracted with chloroform (3 x 100 mL) and the combined chloroform layer was washed with water, brine and dried over sodium sulfate. The solution was filtered and evaporated the solvent. The residue was chromatographed over silica gel using hexane-ethyl acetate (92:8) as eluent to give the product as a pale yellow color solid (1.1 g, 50%), mp 130-1320C. 1H NMR (400 MHz, DMSO-de): δ 7.62-7.65 (2H, m), 7.38-7.48 (3H, m), 7.00 (IH, s), 4.29 (2H, br s), 3.74 (3H, s); LC-MS (positive ion mode): m/z 234 (M+H)+.
50% Step b:Methyl 3-amino-5-phenylthiophene-2-carboxylate:; To a solution of methyl thioglycolate (1 g, 9.43 mmol) in methanol (5 mL) was added a solution of sodium methoxide (0.5 g, 9.43 mmol) in methanol (5 mL) and stirred for 0.5 h. To the above mixture, a solution of 3-chloro-3-phenylprop-2-enenitrile (1.22 g, 7.5 mmol) in DMF (3.5 mL) was added dropwise for 10 min at rt and stirred the mixture at 60 C. for 2 h. Then, a solution of sodium methoxide (1 g, 18.6 mmol) in methanol (10 mL) was added dropwise at rt and stirring was continued for 2 h at 60 C. The mixture was allowed to rt and poured into cold water and stirred for 15 min. The solution was extracted with chloroform (3×100 mL) and the combined chloroform layer was washed with water, brine and dried over sodium sulfate. The solution was filtered and evaporated the solvent. The residue was chromatographed over silica gel using hexane-ethyl acetate (92:8) as eluent to give the product as a pale yellow color solid (1.1 g, 50%), mp 130-132 C. 1H NMR (400 MHz, DMSO-d6): δ 7.62-7.65 (2H, m), 7.38-7.48 (3H, m), 7.00 (1H, s), 4.29 (2H, br s), 3.74 (3H, s); LC-MS (positive ion mode): m/z 234 (M+H)+.
With methanol; sodium; for 0.5h;Reflux; General procedure: POCl3 (26.1 g, 0.17 mol) was added dropwise to DMF (24.9 g, 0.34 mol) maintaining the temperature beyond 25 C (cooling in ice bath) and stirred for additional 15 min. The acetophenone I (85.0 mmol) was added slowly and the temperature was kept between 40 and 60 C. After complete addition, the mixture was stirred for 30 min at room temperature. Hydroxylamine hydrochloride (23.6 g,0.34 mol) was carefully added portionwise (exothermic reaction) and the reaction was stirred for additional 30 min without heating. After cooling to room temperature, the mixture was poured into ice water (300 mL). The precipitated b-chloro-cinnamonitrile was collected by filtration, washed with H2O(2 50 mL) and dried under reduced pressure over CaCl2. In the next step sodium (1.93 g, 84.0 mmol) was dissolved in MeOH(85 mL) and methylthioglycolate (6.97 g, 65.6 mmol) was added to the stirred solution. The b-chloro-cinnamonitrile (61.1 mmol) was added and the mixture was heated to reflux for 30 min. After cooling to room temperature, the mixture was poured into icewater (300 mL). The precipitated solid was collected by filtration, washed with H2O (2 50 mL) and dried under reduced pressure over CaCl2. If necessary, recrystallisation from EtOH was performed.
With sodium; In methanol; for 0.5h;Reflux; General procedure: POCl3 (26.1 g, 0.17 mol) was added dropwise to DMF (24.9 g, 0.34 mol) maintaining the temperature beyond 25 C (cooling in ice bath) and stirred for additional 15 min. The acteophenon I (85.0 mmol) was added slowly and the temperature was kept between 40 and 60 C. After complete addition, the mixture was stirred for 30 minutes at room temperature. Hydroxylamine hydrochloride (23.6 g, 0.34 mol) was carefully added portionwise (exothermic reaction) and the reaction was stirred for additional 30 min without heating. After cooling to room temperature, the mixture was poured into ice water (300 mL). The precipitated β-chloro-cinnamonitrile was collected by filtration, washed with H2O (2 x 50 mL) and dried under reduced pressure over CaCl2. In the next step sodium (1.93 g, 84.0 mmol.) was dissolved in MeOH (85 mL) and methyl thioglycolate (6.97 g, 65.6 mmol) was added to the stirred solution. The β-chloro-cinnamonitrile (61.1 mmol) was added and the mixture was heated to reflux for 30 min. After cooling to room temperature, the mixture was poured in ice water (300 mL). The precipitated solid was collected by filtration, washed with H2O (2 x 50 mL) and dried under reduced pressure over CaCl2. If necessary, recrystallisation was performed from EtOH.

  • 57
  • [ 100063-22-7 ]
  • [ 1148157-86-1 ]
YieldReaction ConditionsOperation in experiment
67% To a stirring solution of <strong>[100063-22-7]methyl 3-amino-5-phenylthiophene-2-carboxylate</strong> 82 (1.166 g, 5 mmol) in water (14 niL) and concentrated hydrochloric acid (7 mL) cooled to O0C was added a solution of sodium nitrite (0.431 g, 6.25 mmol) in water (2 mL). The reaction mixture was stirred for 30 min then the resulting solution was poured into a solution of CuCl (1.732 g, 17.50 mmol) in concentrated hydrochloric acid (20 mL) still at O0C. The reaction was allowed to slowly warm to room temperature over 4 h then poured into ice cold water and extracted with ether (3x). The combined organic phases were washed with water, dried over Na2SO4, filtered and concentrated under reduced pressure to afford methyl 3-chloro-5- phenylthiophene-2-carboxylate 83 as a white solid (0.850 mg, 67% yield) after purification by ISCO (40 g column, 5 to 40% ethyl acetate in hexane). LRMS (ESI) : (calc) 252.72 (found) 253.06 (MH)+
51% General procedure: The appropriate 3-amino-2-thenoate 1 (14 mmol) and TsOH·H2O (10.64 g, 56 mmol) were added to a mixture of acetonitrile (100 ml) and water (25 ml). The mixture was heated until a homogeneous solution was obtained, and then cooled in an ice bath with vigorous stirring to obtain a finely dispersed precipitate of the aminium tosylate salt. The solution of NaNO2 (1.10 g, 16 mmol) in water (4 ml) was added in one portion to theobtained suspension. The resulting dark-red solution was added dropwise to the boiled suspension of CuCl (6.93 g, 70 mmol) in acetonitrile (40 ml) under the inert atmosphere.The mixture was boiled for 5 minutes, while nitrogen was observed, after that it was diluted with water (300 ml) and extracted with methylene chloride (3 × 40 ml). The organic layers were combined, dried with K2CO3, passed through a short layer of SiO2, and then concentrated under reduced pressure. The resulting residue of 2 was recrystallized from ethyl acetate : isopropanol (1:1, v/v), except for 2, which was obtained in analytically pure form after the column chromatography.
  • 58
  • [ 32315-10-9 ]
  • [ 87120-72-7 ]
  • [ 100063-22-7 ]
  • [ 1312600-37-5 ]
YieldReaction ConditionsOperation in experiment
B1. Tert -butyl 4-([2-(methoxycarbonyl)-5-phenylthiophen-3-yl]carbamoyl}amino)piperidine- 1 -carboxylateTo a solution of triphosgene (421 mg) in THF (15 ml) under nitrogen atmosphere was added at 0C a solution of 3-amino-5-phenylthiophene-2-carboxylate (1.00 g) in THF (10 ml) within 2 h. The mixture was stirred at 0C for 1 h and at RT for additional 14 h. The resulting suspension was cooled to 0C and a solution of tert-butyl 4-aminopiperidine-1 -carboxylate (867 mg) in THF (10 ml) was added drop- wise. After 15 min at 0C DIPEA (1.75 ml) was slowly added. The reaction mixture was stirred for 15 min at 0C and for 2.5 h at RT and then washed with an aqueous sodium chloride solution (5 % w/w, three times with 20 ml each) and with brine (20 ml). The organic layer was dried over magnesium sulfate. All volatile materials were removed in vacuo to give the title compound as a solid. MS: calc: C23H29N3O5S (459.56) found: [MH+] = 459.98; [MNa+] = 482.22
  • 59
  • [ 100063-22-7 ]
  • [ 478028-23-8 ]
YieldReaction ConditionsOperation in experiment
With tert.-butylnitrite; copper(ll) bromide; In acetonitrile; at 65℃; for 1h; Step 6. Synthesis of thyl esterTo a 250 round bottom flask equipped with refluxing condenser was added CuBr2 (1 1 .5 g, 51 mmol, 1 .2 equiv), CH3CN (250 mL) and t-butyl nitrite (6.63 g, 64.3 mmol, 1 .5 equiv). The solution was heated at 65 C and to this solution was added a solution of 3-amino-5-phenyl- thiophene-2-carboxylic acid methyl ester (10.0 g, 42.0 mmol) in CH3CN (50 mL). The resulting mixture was heated at 65 C for 1 hour. The reaction mixture was then cooled at room temperature and added to 1 .0 N HCI aq. solution. EtOAc was added and the phases were separated. The aqueous layer was extracted with EtOAc. The organic layer was washed with water, brine, dried (Na2S04) and concentrated. The residue was purified by silica gel to give product 3-bromo-5-phenyl-thiophene-2-carboxylic acid methyl ester 7.5 g.
  • 60
  • [ 100063-22-7 ]
  • [ 15971-92-3 ]
  • [ 1356457-48-1 ]
YieldReaction ConditionsOperation in experiment
Step 1. 3-(1 -Cyclohexyl-2-ethoxycarbonyl-ethylamino)-5-phenyl-thiophene-2 -carboxylic acid methyl ester To a solution of 3-Cyclohexyl-3-oxo-propionic acid ethyl ester (1 .0 g, 5.0 mmol, 1 .0 equiv) in THF (5.0 mL) was added 3-Amino-5-phenyl-thiophene-2-carboxylic acid methyl ester (1 .17 g, 5.0 mmol, 1 .0 equiv) and SnBu2CI2 (0.15 g, 0.50 mmol, 0.1 equiv) at room temperature. After stirred at room temperature for 5 minutes, the solution was added PhSiH3. The resulting reaction mixture was stirred at 65 C under N2 for 18 hours, after which the solution was concentrated under vacuum and the residue was purified by silica gel column chromatography EtOAc/heptane, 10-60% to give product (0.7 g). MS: 416 [M+H+].
  • 61
  • [ 16076-61-2 ]
  • [ 100063-22-7 ]
  • [ 1356457-45-8 ]
YieldReaction ConditionsOperation in experiment
15% With phenylsilane; dibutyltin chloride; In 1,4-dioxane; at 120℃; for 2h;Microwave irradiation; A flask was charged with 3-amino-5-phenyl-thiophene-2-carboxylic acid methyl ester (515 mg, 2.2 mmol, 1 .0 equiv), 5-cyclohexyl-5-oxo-pentanoic acid ethyl ester (500 mg, 2.2 mmol, 1 .0 equiv), phenyl silane (240 mg, 2.2 mmol, 1 .0 equiv), dibutyltin dichloride (67 mg, 0.22 mmol, 0.1 equiv) and dioxane (2.0 mL). The resulting solution was heated at 120 C with microwave for 2 hours. The solution was then concentrated and the residue was purified by silica gel column chromatography, EtOAc/heptane 5% to 40%, to give oil that contained starting material. The material was further purified with silica gel column chromotography, EtOH/DCM 2%to 10% to give product 150 mg (yield 15%).
  • 62
  • [ 100063-22-7 ]
  • [ 1383385-18-9 ]
  • 63
  • [ 100063-22-7 ]
  • [ 1383383-50-3 ]
  • 64
  • [ 100063-22-7 ]
  • [ 1243356-28-6 ]
  • 65
  • [ 100063-22-7 ]
  • [ 1383385-20-3 ]
  • 66
  • [ 100063-22-7 ]
  • [ 1383385-21-4 ]
  • 67
  • [ 100063-22-7 ]
  • [ 1383385-22-5 ]
  • 68
  • [ 100063-22-7 ]
  • [ 1383385-23-6 ]
  • 69
  • [ 100063-22-7 ]
  • [ 478028-46-5 ]
YieldReaction ConditionsOperation in experiment
With tert.-butylnitrite; diiodomethane; In acetonitrile; for 1.5h; [207] To a 50 C solution of diiodomethane (9 g, 34 mmol) in CH3CN (30 mL) were added sequentially ieri-butyl nitrite (1.75 g, 17 mmol) followed by methyl 3-amino-5-phenylthiophene-2- carboxylate (001D; 2.64 g, 11.3 mmol). The reaction was stirred for 1.5 hr and then poured into a solution of sodium bisulfite (20 g in 50 mL H20) and stirred for 20 minutes (min). The resulting mixture was extracted with EtOAc and concentrated in vacuo. Silica gel column purification (0-5% EtOAc in hexane) gave 001E as yellow solid. MS calcd: (M+H)+ = 345. MS found: (M+H)+ = 345.
  • 70
  • [ 100063-22-7 ]
  • [ 1383383-72-9 ]
  • 71
  • [ 100063-22-7 ]
  • [ 1383385-27-0 ]
  • 72
  • [ 100063-22-7 ]
  • [ 1383385-28-1 ]
  • 73
  • [ 100063-22-7 ]
  • [ 1383385-29-2 ]
  • 74
  • [ 100063-22-7 ]
  • [ 1383385-30-5 ]
  • 75
  • [ 100063-22-7 ]
  • [ 1383383-80-9 ]
  • 76
  • [ 100063-22-7 ]
  • [ 1383384-86-8 ]
  • 77
  • [ 100063-22-7 ]
  • [ 1383384-87-9 ]
  • 78
  • [ 100063-22-7 ]
  • C28H37NO3S [ No CAS ]
  • 79
  • [ 100063-22-7 ]
  • [ 1383385-66-7 ]
  • 80
  • [ 100063-22-7 ]
  • [ 1383384-88-0 ]
  • 81
  • [ 100063-22-7 ]
  • [ 1383385-67-8 ]
  • 82
  • [ 100063-22-7 ]
  • [ 1383385-68-9 ]
  • 83
  • [ 100063-22-7 ]
  • [ 1383384-89-1 ]
  • 84
  • [ 100063-22-7 ]
  • [ 1383384-90-4 ]
  • 85
  • [ 100063-22-7 ]
  • [ 1383383-10-5 ]
  • 86
  • [ 402-43-7 ]
  • [ 100063-22-7 ]
  • [ 1393719-04-4 ]
YieldReaction ConditionsOperation in experiment
48% With PdCl(C3H5)(dppb); potassium acetate; In N,N-dimethyl acetamide; at 120℃; for 20h;Inert atmosphere; 4-(Trifluoromethyl)bromobenzene (0.225 g, 1 mmol), <strong>[100063-22-7]methyl 3-amino-5-phenylthiophene-2-carboxylate</strong> (0.466 g, 2 mmol) and KOAc (0.196 g, 2 mmol) at 120 C during 20 h in DMAc (3 mL) in the presence of PdCl(C3H5)(dppb) (12.2 mg, 0.02 mmol) under argon affords 49 in 48% (0.181 g) yield.
  • 88
  • [ 14002-51-8 ]
  • [ 100063-22-7 ]
  • [ 477326-27-5 ]
YieldReaction ConditionsOperation in experiment
43% With dmap; at 20℃; for 18h;Inert atmosphere; General procedure: The appropriate alkyl aminobenzoate or alkyl aminothiophenecarboxylate (1equiv) and a catalytic amount of DMAP were added to a suspension of the acyl chloride (1.5equiv) in pyridine under a N2 atmosphere. The reaction mixture was stirred for 18h at room temperature and 2M HCl was added. The mixture was extracted with EtOAc, the combined organic layers washed with saturated NaHCO3 and dried over MgSO4. For purification the solvent was evaporated and the remaining solid was suspended in MeOH. After filtration the precipitate was washed with MeOH (and EtOAc in case of 45a) to provide the pure compound.
  • 89
  • [ 61771-79-7 ]
  • [ 100063-22-7 ]
  • C22H23NO2S [ No CAS ]
  • 90
  • C12H20O2 [ No CAS ]
  • [ 100063-22-7 ]
  • C23H25NO2S [ No CAS ]
  • 91
  • [ 100063-22-7 ]
  • [ 16182-04-0 ]
  • C16H16N2O4S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
In N,N-dimethyl-formamide; at 20℃; General procedure: To a solution of methyl-3-amino-5-p-tolylthiophene-2-carboxylate in DMF (40 mL) was added ethoxycarbonyle isothiocyanate(1 eq). The solution was left stirring at room temperature overnight. During this reaction, a thiourea carbamate intermediate was formed and was not isolated. To the reaction mixture were then added triethylamine (3 eq), terbutylamine (2 eq) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, hydrochloride (EDCI,HCl) (1.2 eq). The solution was then heated under reflux for 2 h. The solvent was removed under reduced pressure. Water (10 mL) was then added to the reaction mixture and the precipitated solid obtained was filtered, washed with diethyl ether and recrystallized from acetonitrile to give the corresponding 2-alkyl(dialkyl)aryl-2-aminothieno[3,2-d]pyrimidin-4(3H)-one derivative.
  • 92
  • [ 100063-22-7 ]
  • [ 1019164-57-8 ]
  • 93
  • [ 100063-22-7 ]
  • [ 1694-29-7 ]
  • methyl 3-[2-(1-chloro-2-oxopropylidene)hydrazinyl]-5-phenylthiophene-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% This compound was prepared by the following two-step procedure: Step (i): Methyl 3-amino-5-phenyl-2-thiophenecarboxylate (3) (2.33 g, 10mmol) was dissolved in 6 N aqueous hydrochloric acid (20mL). To this cooled (0-4 C) and stirred solution was added dropwise, a solution of sodium nitrite (0.83 g, 12 mmol) inwater (2 mL). Stirring was then continued for 20-30 min and the resulting fresh cold thiophene-3-diazonium chloride solution was used immediately as such for the following coupling reaction. Step (ii): The cold thiophene-3-diazonium chloride solution, prepared above in step (i), was poured onto a cold solution (-5 C/ice-salt bath) of 3-chloro-2,4-pentanedione (1.35 g, 10 mmol) in ethanol-water (20 mL, 3:1 v/v) containing sodium acetate (18 g). The resulting orange-coloured mixture was then diluted with cold water (200 mL), the precipitated solid product collected by suction filtration, washed with cold water (5 × 15 mL), dried and recrystallized from dichlomethane/n-hexane. Yield: 88 %, m.p.: 176-180 C. 1H NMR (500 MHz,CDCl3): 2.61 (s, 3H, O=C-CH3), 3.95 (s, 3H, CO2-CH3),7.45 (m, 3H, H-3'/H-5' + H-4'), 7.49 (s, 1H, H-4), 7.69 (d, J =7.2 Hz, 2H, H-2'/H-6'), 10.89 (s, 1H, N-H, exchangeable withD2O). 13C NMR (125 MHz, CDCl3): 25.4 (O=C-CH3), 52.2(CO2-CH3), 105.3 (C-2), 113.5 (C-4), 126.2 (C-2'/C-6'), 127.5(-N=C-Cl), 129.2 (C-3'/C-5'), 129.6 (C-4'), 132.8 (C-1'),148.8 (C-5), 150.6 (C-3), 164.4 (CO2Me), 188.3 (O=C-Me).HRMS ((+)ESI): m/z = 359.02278 (calcd. 359.02276 forC16H1335ClN2NaO3S, [M+ Na]+); m/z = 361.01982 (calcd.361.01978 for C16H1337ClN2NaO3S, [M + 2 + Na]+); m/z =337.04064 (calcd. 337.04082 for C15H1435ClN2O3S, [M + H]+);m/z = 339.03769 (calcd. 339.03784 for C15H1437ClN2O3S, [M +2 + H]+); m/z = 673.07407 (calcd. 673.07436 for C30H2735Cl2N4O6S2,[2M + H]+); m/z = 675.07065 (calcd. 675.07137 forC30H2735Cl37ClN4O6S2, [2M + 2 + H]+); m/z = 677.06670 (calcd.677.06712 for C30H2737Cl2N4O6S2, [2M + 4 + H]+). Anal. calcd.for C15H13N2O3SCl (336.79): C 53.49, H 3.89, N 8.32; found:C 53.28, H 3.77, N 8.25.
  • 94
  • [ 100063-22-7 ]
  • [ 3019-71-4 ]
  • methyl 5-phenyl-3-(3-(trichloromethyl)ureido)thiophene-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
96% In tetrahydrofuran; at 20℃; for 2h; A solution of <strong>[100063-22-7]methyl 3-amino-5-phenylthiophene-2-carboxylate</strong> 4 (2.065 g, 8.85 mmol) and 2,2,2-trichloroacetyl isocyanate (1.049 mL, 8.85 mmol) in THF (10 mL) was stirred for 2h at room temperature. The mixture was diluted with H2O and AcOEt, the precipitate was collected and washed with hexane to give the title compound as white solid (3.33 g, 96%). 1H NMR (DMSO-d6) δ = 3.89 (s, 3H), 7.50 (m, 3H), 7.75 (m, 2H), 8.30 (1H, s), 11.58 (1H, br), 12.11 (1H, br).
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