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Product Details of [ 4701-17-1 ]

CAS No. :4701-17-1 MDL No. :MFCD00005432
Formula : C5H3BrOS Boiling Point : -
Linear Structure Formula :- InChI Key :GFBVUFQNHLUCPX-UHFFFAOYSA-N
M.W : 191.05 Pubchem ID :78428
Synonyms :

Calculated chemistry of [ 4701-17-1 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 8
Num. arom. heavy atoms : 5
Fraction Csp3 : 0.0
Num. rotatable bonds : 1
Num. H-bond acceptors : 1.0
Num. H-bond donors : 0.0
Molar Refractivity : 37.41
TPSA : 45.31 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.75 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.46
Log Po/w (XLOGP3) : 2.42
Log Po/w (WLOGP) : 2.32
Log Po/w (MLOGP) : 1.19
Log Po/w (SILICOS-IT) : 3.38
Consensus Log Po/w : 2.15

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.95
Solubility : 0.217 mg/ml ; 0.00113 mol/l
Class : Soluble
Log S (Ali) : -3.01
Solubility : 0.185 mg/ml ; 0.000968 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.47
Solubility : 0.647 mg/ml ; 0.00339 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.08

Safety of [ 4701-17-1 ]

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

Application In Synthesis of [ 4701-17-1 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 4701-17-1 ]
  • Downstream synthetic route of [ 4701-17-1 ]

[ 4701-17-1 ] Synthesis Path-Upstream   1~32

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Reference: [1] Patent: US5717092, 1998, A,
  • 2
  • [ 98-03-3 ]
  • [ 4701-17-1 ]
YieldReaction ConditionsOperation in experiment
98% With N-Bromosuccinimide In chloroform at 20℃; 2.1.1
Synthesis of 5-bromo-2-thiophenecarbaldehyde
To a solution of 2-thiophenecarboxaldehyde (6.0 g, 53.5 mol) in anhydrous CHCl3 (125 mL), N-bromosuccinimide (10.4 g, 58.9 mmol) was slowly added, and then the reaction mixture was stirred for overnight at room temperature.
The reaction mixture was extracted with CHCl3, and the organic phase was washed with deionized water, dried over Na2SO4, filtered, and evaporated to dryness to give the crude product.
Column chromatography was performed on silica gel using CHCl3 as the eluent, which affords the pure product as a colorless oil (10.0 g, 98percent).
1H NMR (400 MHz, CDCl3): δ 7.20 (d, H, J = 4.0 Hz), 7.53 (d, H, J = 8.0 Hz), 9.79 (s, H).
35% With acetic acid In chloroform at 0 - 20℃; for 13 h; Darkness NBS (1.5 eq, 5.8g, 33 mmol) was added to a solution of thiophene-2-carbaldehyde (1.0 eq., 2 mL, 22 mmol) in a mixture of chloroform/AcOH (10:1, 22 mL) at 0 C in the absence of light. The reaction mixture was stirred at 0 C for 1h. Then the mixture was allowed to warm to rt for 12 hours. The reaction was quenched with an aqueous sat. NaHCO3 solution. The organic layer was washed with brine, dried (MgSO4), filtered, and the solvents were evaporated in vacuo. The crude product was purified (FCC, SiO2, 0-100 percent EtOAc in heptane) to provide the title compound (1.4 g, 35percent).1H NMR (300 MHz, CDCl3) δ 9.76 (s, 1H), 7.51 (d, J = 4.0 Hz, 1H), 7.18 (d, J = 4.0 Hz, 1H).
Reference: [1] Physica B: Condensed Matter, 2017, vol. 519, p. 53 - 58
[2] Tetrahedron, 2007, vol. 63, # 37, p. 9188 - 9194
[3] Tetrahedron Letters, 2005, vol. 46, # 12, p. 1989 - 1992
[4] Patent: WO2018/67786, 2018, A1, . Location in patent: Page/Page column 134; 135
[5] Journal of the Chemical Society, 1958, p. 1721
[6] Arkiv foer Kemi, 1955, vol. 8, p. 87
[7] Journal of Materials Chemistry, 2000, vol. 10, # 9, p. 2069 - 2080
[8] Macromolecules, 2011, vol. 44, # 13, p. 5155 - 5167
[9] Molecular Crystals and Liquid Crystals, 2014, vol. 599, # 1, p. 157 - 162
  • 3
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  • [ 4701-17-1 ]
YieldReaction ConditionsOperation in experiment
87% With dipotassium peroxodisulfate; iron(II) acetylacetonate In water; acetonitrile at 80℃; for 6 h; A 25 mL reaction flask was charged with ferrous acetylacetonate (0.025 mmol)Polymethylhydrogensiloxane (0.75 mmol),(0.25 mmol), Id (0.25 mmol), acetonitrile (lmL), water (lmL), the reaction mixture at 80 ° CThe reaction was carried out for 6 h. At the end of the reaction, ammonia water (2 mL) was added to remove the poly (methylene oxide), and 10 mL of saturated brine was added,Extraction (10 mL X 3), the organic phase was combined and the solvent was removed under reduced pressure. Column chromatography gave 87percent yield.
Reference: [1] Patent: CN107216242, 2017, A, . Location in patent: Paragraph 0032; 0034
  • 4
  • [ 1003-09-4 ]
  • [ 68-12-2 ]
  • [ 4701-17-1 ]
YieldReaction ConditionsOperation in experiment
84.1%
Stage #1: at 0℃; for 1 h; Inert atmosphere
Stage #2: at 90℃; for 4 h;
To the cold solvent dry DMF (20 ml) at 0 °C, POCl3 (18 ml) was added dropwise. The solution was stirred for 1 h. Then 2-bromothiophene (3) (1.94 ml, 20 mmol) dissolved in 1,2-dechloroethane (30 ml) was injected. The reaction was kept at 90 °C for 4 h under N2. After cooling to room temperature, the reaction mixture was poured to 200 ml ice water, neutralized with saturated NaOH solution, and then extracted with dichloromethane twice. The combined organic layer was washed with H2O and brine, dried over Na2SO4, and evaporated under reduced pressure. The crude product was purified by column chromatography (petroleum/EtOAc=5/1) to obtain compound 4 (3196 mg, 84.1percent) as yellow liquid. MS(EI): m/z=190 (M+). 1H NMR (CDCl3, 400 M Hz) δ/ppm: 9.78 (s, 1H), 7.52 (d, 1H), 7.19 (d,1H).
Reference: [1] Journal of Materials Chemistry A, 2015, vol. 3, # 5, p. 2108 - 2119
[2] Tetrahedron, 2012, vol. 68, # 44, p. 9113 - 9118
[3] Journal of Materials Chemistry A, 2013, vol. 1, # 34, p. 10008 - 10015
[4] Organic Preparations and Procedures International, 2004, vol. 36, # 4, p. 337 - 340
[5] Chemical Communications, 2009, # 18, p. 2499 - 2501
[6] Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences, 2012, vol. 67, # 4, p. 285 - 294
[7] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1980, vol. 16, # 3, p. 230 - 233[8] Khimiya Geterotsiklicheskikh Soedinenii, 1980, vol. 16, # 3, p. 315 - 319
[9] Patent: DE953082, 1953, ,
  • 5
  • [ 636-72-6 ]
  • [ 98-03-3 ]
  • [ 4701-17-1 ]
Reference: [1] Journal of the American Chemical Society, 2004, vol. 126, # 13, p. 4112 - 4113
  • 6
  • [ 3141-27-3 ]
  • [ 68-12-2 ]
  • [ 4701-17-1 ]
Reference: [1] Tetrahedron Letters, 2001, vol. 42, # 29, p. 4841 - 4844
[2] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1986, p. 1755 - 1758
[3] Organic Letters, 2008, vol. 10, # 14, p. 2991 - 2993
[4] Journal of Materials Chemistry, 2008, vol. 18, # 15, p. 1756 - 1764
  • 7
  • [ 79387-71-6 ]
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Reference: [1] RSC Advances, 2015, vol. 5, # 111, p. 91594 - 91600
[2] New Journal of Chemistry, 2017, vol. 41, # 6, p. 2372 - 2377
  • 8
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Reference: [1] European Journal of Organic Chemistry, 2012, # 2, p. 260 - 263
  • 9
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Reference: [1] RSC Advances, 2018, vol. 8, # 56, p. 32055 - 32062
  • 10
  • [ 1448723-46-3 ]
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Reference: [1] Chemical Science, 2013, vol. 4, # 3, p. 1111 - 1119
  • 11
  • [ 765-50-4 ]
  • [ 98-03-3 ]
  • [ 4701-17-1 ]
Reference: [1] Synthetic Communications, 2010, vol. 40, # 8, p. 1106 - 1114
  • 12
  • [ 1003-09-4 ]
  • [ 93-61-8 ]
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Reference: [1] Journal of the American Chemical Society, 1950, vol. 72, p. 1422
[2] Journal of Organic Chemistry, 1949, vol. 14, p. 405,409
[3] Journal of Applied Spectroscopy, 2002, vol. 69, # 2, p. 230 - 237[4] Zhurnal Prikladnoi Spektroskopii, 2002, vol. 69, # 2, p. 200 - 206
  • 13
  • [ 7311-46-8 ]
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Reference: [1] Journal of the American Chemical Society, 1953, vol. 75, p. 988
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  • [ 7311-63-9 ]
  • [ 4701-17-1 ]
Reference: [1] Chemical Science, 2013, vol. 4, # 3, p. 1111 - 1119
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  • [ 1448723-45-2 ]
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Reference: [1] Chemical Science, 2013, vol. 4, # 3, p. 1111 - 1119
  • 16
  • [ 3141-27-3 ]
  • [ 109-94-4 ]
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Reference: [1] Justus Liebigs Annalen der Chemie, 1912, vol. 393, p. 224
  • 17
  • [ 98-03-3 ]
  • [ 67-66-3 ]
  • [ 7726-95-6 ]
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Reference: [1] Journal of the Chemical Society, 1958, p. 1721
[2] Arkiv foer Kemi, 1955, vol. 8, p. 87
  • 18
  • [ 4701-17-1 ]
  • [ 23784-96-5 ]
Reference: [1] Chemical Communications, 2015, vol. 51, # 18, p. 3842 - 3845
  • 19
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  • [ 7311-63-9 ]
Reference: [1] Journal of Medicinal Chemistry, 1992, vol. 35, # 6, p. 1109 - 1116
[2] Bulletin de la Societe Chimique de France, 1967, p. 4115 - 4120
[3] Journal of Medicinal Chemistry, 2002, vol. 45, # 23, p. 5005 - 5022
[4] Chemistry - A European Journal, 2005, vol. 11, # 16, p. 4735 - 4742
[5] Patent: US5726312, 1998, A,
[6] Patent: US5739141, 1998, A,
[7] Patent: WO2012/56478, 2012, A1, . Location in patent: Page/Page column 72
[8] Journal of Materials Chemistry A, 2013, vol. 1, # 34, p. 10008 - 10015
[9] New Journal of Chemistry, 2018, vol. 42, # 1, p. 598 - 612
  • 20
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  • [ 62224-19-5 ]
Reference: [1] Journal of Medicinal Chemistry, 1992, vol. 35, # 6, p. 1109 - 1116
[2] Journal of Materials Chemistry A, 2013, vol. 1, # 34, p. 10008 - 10015
  • 21
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  • [ 5751-83-7 ]
Reference: [1] Patent: US4923884, 1990, A,
[2] Patent: EP272921, 1991, B1,
  • 22
  • [ 4701-17-1 ]
  • [ 19163-24-7 ]
Reference: [1] Journal of Medicinal Chemistry, 1997, vol. 40, # 11, p. 1585 - 1599
[2] Heterocycles, 2014, vol. 89, # 2, p. 453 - 464
  • 23
  • [ 4701-17-1 ]
  • [ 124-40-3 ]
  • [ 24372-46-1 ]
YieldReaction ConditionsOperation in experiment
82.5% at 100℃; for 12 h; Synthesis of 5-dimethylamino-2-thiophenecarboxyaldehyde (30)
5-Bromo-2-thiophenecarboxyaldehyde (1 g, 5.23 mmol) and dimethylamine (1.64 mL, 15.69 mmol) were mixed, followed by addition of purified water (3 mL).
The mixture was reacted at 100°C for 12 h, and then the layers were separated with chloroform (50 mL x 2) and purified water (50 mL), the chloroform layer was dried with anhydrous sodium sulfate, and then the solvent was evaporated under reduced pressure.
The residue was subjected to medium-pressure preparative chromatography using ethyl acetate/hexane (1/1) as an elution solvent to obtain Compound 30.
Yield 670 mg (yield rate 82.5percent).
1H NMR (300 MHz, CDCl3) δ 3.10 (s, 6H), 5.96 (s, 1H), 7.45 (s, 1H), 9.44 (s, 1H).
60% With toluene-4-sulfonic acid In water at 100℃; for 24 h; To a 100 mL round bottom flask was added 5-bromothiophene-2-carbaldehyde (6 g, 32 mmol)And dimethylamine aqueous solution (16.2 mL, content 40percent, 128 mmol)To a solution of p-toluenesulfonic acid (0.55 g, 3.2 mmol) as a catalyst,The reaction was refluxed at 100 ° C for about 24 h,Dimethylamine is volatile,Add about 8 mL of dimethylamine aqueous solution every 6 hours,Process point board tracking,Until 5-bromothiophene-2-carbaldehyde is completely reacted;After completion of the reaction, the mixture was cooled to room temperature,Down to about 60 mL of deionized water,Stirred at room temperature for 0.5 h,Extracted with 3 x 40 mL of dichloromethane;After extraction, the organic phase was combined,Dried over anhydrous sodium sulfate,Filter,Steaming concentrated solution;Using silica gel column chromatography separation and purification (eluent:Ethyl acetate / petroleum ether = 1/1),Finally, a dark red target product (yield of about 60percent) was obtained.
Reference: [1] Synlett, 1998, # 4, p. 383 - 384
[2] Patent: EP2030635, 2009, A1, . Location in patent: Page/Page column 26; 50
[3] Chemical Communications, 2015, vol. 51, # 96, p. 17124 - 17127
[4] Patent: CN107090190, 2017, A, . Location in patent: Paragraph 0046; 0047; 0048; 0049
[5] Journal of the American Chemical Society, 2001, vol. 123, # 12, p. 2810 - 2824
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YieldReaction ConditionsOperation in experiment
82.5% With dimethyl amine In hexane; water; ethyl acetate Synthesis of 5-dimethylamino-2-thiophenecarboxyaldehyde (30)
5-Bromo-2-thiophenecarboxyaldehyde (1 g, 5.23 mmol) and dimethylamine (1.64 mL, 15.69 mmol) were mixed, followed by addition of purified water (3 mL).
The mixture was reacted at 100° C. for 12 h, and then the layers were separated with chloroform (50 mL*2) and purified water (50 mL), the chloroform layer was dried with anhydrous sodium sulfate, and then the solvent was evaporated under reduced pressure.
The residue was subjected to medium-pressure preparative chromatography using ethyl acetate/hexane (1/1) as an elution solvent to obtain Compound 30.
Yield 670 mg (yield rate 82.5percent).
1H NMR (300 MHz, CDCl3) δ 3.10 (s, 6H), 5.96 (s, 1H), 7.45 (s, 1H), 9.44 (s, 1H).
Reference: [1] Patent: US2010/278733, 2010, A1,
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Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 16, p. 4823 - 4827
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  • [ 2160-62-5 ]
YieldReaction ConditionsOperation in experiment
82% With tert.-butylhydroperoxide; ammonium acetate; iodine; sodium carbonate In ethanol at 50℃; for 15 h; In a 25 mL two-necked round bottom flask equipped with a thermometer and a magnetic stirrer was added 4 mmol of 5-bromothiophene-2-carbaldehyde (1-20)), 6 mmol of NH4OAc, 4 mmol of Na2CO3, 4.4 mmol of TBHP, 0.1 mmol of I2, 5 mL of absolute ethanol Solvent, followed by placing the reaction flask in an oil bath preheated to 50 ° C and opening the magnetic stirrer for 15 h. The reaction solution By adding sodium thiosulfate solution, stirring, and then extracting with ether, separating the organic layer, and removing the solvent under reduced pressure, The eluate was collected with the mixture of ethyl acetate / petroleum ether in a volume ratio of 1: 100 as the eluent, and the eluate containing the target compound was collected. The solvent was distilled off to give 5-bromothiophene-2-carbonitrile with an isolated yield of 82percent.
58%
Stage #1: With hydroxylamine hydrochloride In pyridine; ethanol for 2 h; Nitrogen atmosphere; heating/reflux
Stage #2: With copper diacetate In acetonitrile for 3 h; Heating / reflux
5-Bromo-2-thiophenecarbonitrile: A mixture of 5-bromo-2-thiophenecarboxaldehyde (96.0 g, 500 mmol), hydroxylamine hydrochloride (111.9 g, 500 mmol), pyridine (500 mL), and ethanol (500 mL) was heated under nitrogen at reflux for two hours. The reaction mixture was cooled to ambient temperature and concentrated in vacuo to give an oil. The crude product was triturated twice with ice water and the solid obtained was collected on a filter. A mixture of a portion of the above solid (44.31 g, 215 mmol), copper (II) acetate monohydrate (4.2 g, 21 mmol) in acetonitrile (1.4 L) was heated at reflux for three hours. The solvent was removed in vacuo and the residue was dissolved in ethyl acetate. The solution was washed with 5percent aqueous sulfuric acid (2.x.30 mL), water (2.x.30 mL), brine (20 mL), and dried (MgSO4). The solvent was removed in vacuo and the residue was dissolved in a minimum amount of chloroform (1 L) and allowed to crystallize. The crystals obtained was collected on a filter and the filtrate was concentrated and purified by a chromatography (silica gel, chloroform) to give the subtitled compound as an off-white solid (31.5 g combined, 58percent). IR (film) cm1 2200. 1H-NMR (CDCl3) δ 7.39-7.38 (d, 1H, J=4.1 Hz), 7.10 (d, 1H, J=4.0 Hz); MS (EI) m/z 187 (M+, 98percent) 189(M+, 100percent).
24% With hydroxylamine-O-sulfonic acid In hexane; water; acetic anhydride; ethyl acetate EXAMPLE 8
Preparation of 5-Bromo-2-Thiophenecarbonitrile STR97
Hydroxylamine-O-sulfonic acid (17.58 g, 157 mmol) is added to a solution of 5-bromo-2-thiophenecarboxaldehyde (15.00 g, 78.5 mmol) in water and acetonitrile.
The reaction mixture is stirred for 17 hours, poured into water and extracted with ether and ethyl acetate.
The combined organic extracts are washed sequentially with water and brine, dried over MgSO4 and concentrated in vacuo to give a brown, oily solid.
A solution of the oily solid in acetic anhydride is refluxed for five hours, concentrated in vacuo, poured into water and extracted with ether.
The combined organic extracts are washed sequentially with water, half-saturated sodium hydrogen carbonate solution and brine, dried over MgSO4 and concentrated in vacuo to obtain a brown oil.
Flash chromatography of the oil using silica gel and a 15percent ethyl acetate in hexane solution gives the title product as a yellow oil (3.60 g, 24percent).
24% With hydroxylamine-O-sulfonic acid In hexane; water; acetic anhydride; ethyl acetate EXAMPLE 8
Preparation of 5-Bromo-2-thiophenecarbonitrile STR97
Hydroxylamine-O-sulfonic acid (17.58 g, 157 mmol) is added to a solution of 5-bromo-2-thiophenecarboxaldehyde (15.0 g, 78.5 mmol) in water and acetonitrile.
The reaction mixture is stirred for 17 hours, poured into water and extracted with ether and ethyl acetate.
The combined organic extracts are washed sequentially with water and brine, dried over MgSO4 and concentrated in vacuo to give a brown, oily solid.
A solution of the oily solid in acetic anhydride is refluxed for five hours, concentrated in vacuo, poured into water and extracted with ether.
The combined organic extracts are washed sequentially with water, half-saturated sodium hydrogen carbonate solution and brine, dried over MgSO4 and concentrated in vacuo to obtain a brown oil.
Flash chromatography of the oil using silica gel and a 15percent ethyl acetate in hexane solution gives the title product as a yellow oil (3.6 g, 24percent).
16% With pyridine; ammonium peroxydisulfate; tris(2,2-bipyridine)ruthenium(II) hexafluorophosphate; 4-acetylamino-2,2,6,6-tetramethyl-1-piperidinoxy In acetonitrile at 0.5℃; for 24 h; Molecular sieve; Sealed tube; Irradiation General procedure: To an oven-dried 2 ml reaction vial equipped with a stir bar wasadded the aldehyde 3a (0.136 g, 1 mmol, 1 equiv) and pyridine(0.474 g, 6.0 mmol, 6 equiv), followed by acetonitrile (2 ml, 0.5M in 3a). The vial was then charged with Ru(bpy)3(PF6)2 (0.017g, 0.02 mmol, 0.02 equiv), 2 (0.043 g, 0.20 mmol, 0.20 equiv),(NH4)2S2O8(0.501 g, 2.2 mmol, 2.2 equiv), and activated 3 Åmolecular sieves (ca. 0.2 g), sealed with a cap, and irradiated inblue LED reactor for 24 h. In the absence of fan cooling, the temperatureof the reaction mixture plateaued at approximately 50°C . After the irradiation was complete, the reaction mixturewas quenched with EtOAc and transferred to a separatoryfunnel. Further EtOAc (30 ml) was added, followed by 0.5 MHCl(aq) (30 ml). The layers were separated, and the aqueous layerwas extracted with EtOAc (3 × 20 ml). The organic layers werethen combined and washed with 0.5 M 0.5 M HCl(aq) (2 × 20 ml),saturated aqueous sodium bicarbonate (2 × 20 ml), and finallybrine (20 ml). The organic layer was then dried over sodiumsulfate and the solvent removed in vacuo to afford the crudeproduct. The resulting crude mixture was adhered to silica gelusing 1.5 weight equivalents of SiO2(relative to the theoreticalyield). The dry-packed material was gently added on top of asilica gel plug. The plug was washed with an excess of hexanes(ca. 5 column volumes). The desired product was eluted off theplug via a 90:10 by volume mixture of hexanes/EtOAc (3–4column volumes). The solvent was removed in vacuo by rotaryevaporation affording the pure nitrile 3c (0.066 g, 50percent) as awhite solid.

Reference: [1] Journal of the American Chemical Society, 2011, vol. 133, # 34, p. 13437 - 13444
[2] Advanced Synthesis and Catalysis, 2016, vol. 358, # 7, p. 1157 - 1163
[3] RSC Advances, 2017, vol. 7, # 3, p. 1484 - 1489
[4] Patent: CN106748881, 2017, A, . Location in patent: Paragraph 0052
[5] Patent: US6355648, 2002, B1, . Location in patent: Page column 55
[6] Patent: US5480902, 1996, A,
[7] Patent: US5492925, 1996, A,
[8] Synlett, 2018, vol. 29, # 16, p. 2185 - 2190
[9] Journal of Materials Chemistry, 2000, vol. 10, # 9, p. 2069 - 2080
[10] Synlett, 2011, # 15, p. 2223 - 2227
[11] Angewandte Chemie - International Edition, 2015, vol. 54, # 14, p. 4241 - 4245
[12] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 3, p. 778 - 781
[13] Journal of Organic Chemistry, 2018,
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  • [ 4701-17-1 ]
  • [ 637-81-0 ]
  • [ 238749-50-3 ]
YieldReaction ConditionsOperation in experiment
12.1 g With sodium ethanolate In ethanol; o-xylene at 0℃; for 3.5 h; Inert atmosphere; Reflux Under an argon stream, 5-bromo-2-thiophenecarboxaldehyde (19.1 g, 0.1 mol) and ethyl azidoacetate (51.6 g, 0.4 mol) were dissolved in ethanol (800 mL) in a 2 L four-neck flask, and a 20percent by mass sodium ethoxide ethanol solution (136 g, 0.4 mol) was slowly added dropwise to the obtained solution at 0° C. in an ice bath, followed by stirring for 2 hours.
After the reaction ended, a saturated ammonium chloride aqueous solution was added thereto to adjust the pH to be weakly acidic.
Furthermore, water was added thereto, and the precipitate was collected by filtration, and dried, whereby ethyl 2-azido-3-(5-bromo-thiophen-2-yl)-acrylate was obtained as a yellow solid (obtained amount: 18.4 g, yield: 61.3percent).
Next, ethyl 2-azido-3-(5-bromo-thiophen-2-yl)-acrylate (18.1 g, 60 mmol) was put into a 500 mL egg-plant shaped flask, and dissolved in o-xylene (200 mL), followed by refluxing and stirring for 1.5 hours. After the solution after refluxing and stirring was concentration under reduced pressure, the obtained crude product was recrystallized (solution: hexane and ethyl acetate), then, the resultant product was subjected to suction filtration, and the obtained filtered material was dried, whereby ethyl 2-bromo-4H-thieno [3.2-b]pyrrole-5-carboxylate (d-1) was obtained (obtained amount: 12.1 g, yield: 73.8percent).
Reference: [1] Patent: US2015/158888, 2015, A1, . Location in patent: Paragraph 0075-0080
[2] Chemistry - An Asian Journal, 2015, vol. 10, # 6, p. 1335 - 1343
[3] Patent: US2016/271273, 2016, A1, . Location in patent: Paragraph 0289
  • 28
  • [ 4701-17-1 ]
  • [ 238749-50-3 ]
Reference: [1] Journal of Heterocyclic Chemistry, 1984, vol. 21, p. 215 - 217
[2] Chemistry - An Asian Journal, 2013, vol. 8, # 12, p. 3123 - 3132
[3] Journal of Medicinal Chemistry, 2017, vol. 60, # 5, p. 1673 - 1692
  • 29
  • [ 4701-17-1 ]
  • [ 134135-41-4 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 7, p. 1017 - 1022
[2] Journal of Medicinal Chemistry, 1999, vol. 42, # 18, p. 3557 - 3571
  • 30
  • [ 4701-17-1 ]
  • [ 154593-58-5 ]
Reference: [1] Tetrahedron: Asymmetry, 1997, vol. 8, # 4, p. 527 - 536
[2] Organic Letters, 2016, vol. 18, # 21, p. 5468 - 5471
  • 31
  • [ 5382-16-1 ]
  • [ 4701-17-1 ]
  • [ 207290-72-0 ]
YieldReaction ConditionsOperation in experiment
71% Reflux 5-Bromothiophene-2-carboxaldehyde was placed in a reactor, and water was added thereto. 4-Hydroxypiperidine (3 eq) was added to the reactor, and the mixture was stirred for tens of minutes or overnight under reflux. Immediately after completion of reaction, the reaction mixture was filtered through filter paper, and the filtrate was cooled for tens of minutes with a flow of water and then for several hours with ice. The precipitated crystals were recovered through filtration under suction and washed with cold water. The crystals were dried and dissolved in chloroform. The chloroform solution was dried over sodium sulfate anhydrate, and the dried solution was filtered through a silica gel pad. The filtrate was washed with chloroform until the color thereof became faint. The filtrate was concentrated under reduced pressure until the start of crystallization. n-Hexane was added to the mixture, and stirring was performed overnight at room temperature. The formed crystals were recovered through filtration, washed with n-hexane, and dried under reduced pressure, to thereby yield 5-(4-hydroxypiperidin-1-yl)-thiophene-2-carboxaldehyde. By use of 5-bromothiophene-2-carboxaldehyde (42.30 g) and 4-hydroxypiperidine (67.30 g), amine incorporation was performed according to Production Step 1, to thereby yield 5-(4-hydroxy-piperidin-1-yl)-thiophene-2-carboxaldehyde (yield: 33.00 g, 71percent). The thus-produced 5-(4-hydroxy-piperidin-1-yl)-thiophene-2-carboxaldehyde (10.56 g) and 3,4-dimethoxybenzyl cyanide (8.86 g) were subjected to condensation according to Production Step 2, to thereby yield (Z)-2-(3,4-dimethoxy-phenyl)-3-[5-(4-hydroxy-piperidin-1-yl)-thiophen-2-yl]-acrylonitrile (yield: 13.50 g, 73percent). The thus-produced (Z)-2-(3,4-dimethoxy-phenyl)-3-[5-(4-hydroxy-piperidin-1-yl)-thiophen-2-yl]-acrylonitrile (20.00 g) was dissolved in chloroform (650 mL), and the solution was reacted with pyridine (6.41 g) and bromoacetyl bromide (14.13 g) according to Production Step 3 (Method A), to thereby yield bromo-acetic acid 1-[5-[(Z)-2-cyano-2-(3,4-dimethoxy-phenyl)-vinyl]-thiophen-2-yl]-piperidin-4-yl ester (yield: 23.00 g, 87percent). The thus-produced bromo-acetic acid 1-[5-[(Z)-2-cyano-2-(3,4-dimethoxy-phenyl)-vinyl]-thiophen-2-yl]-piperidin-4-yl ester (2.30 g) was dissolved in chloroform (100 mL), and the solution was reacted with piperidine (533 mg) and triethylamine (658 mg) according to Production Step 4, to thereby yield the title compound (yield: 1.40 g, 60percent).
Reference: [1] Synlett, 1998, # 4, p. 383 - 384
[2] Synthetic Communications, 2000, vol. 30, # 8, p. 1359 - 1364
[3] Patent: EP2218719, 2010, A1, . Location in patent: Page/Page column 7-8
  • 32
  • [ 4701-17-1 ]
  • [ 73183-34-3 ]
  • [ 1040281-83-1 ]
YieldReaction ConditionsOperation in experiment
88.9% With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; potassium acetate In 1,4-dioxane at 80℃; for 6 h; Inert atmosphere A solution of 4 (1.68 g, 8.8 mmol), bis(pinacolato)diboron (3.4 g, 13.2 mmol), PdCl2(dppf) (756 mg, 0.88 mmol), and KOAc (2.587 g, 26.4 mmol) in degassed 1,4-dioxane (60 ml) was stirred at 80 °C for 6 h under N2. The reaction was quenched by adding water, and extracted by dichloromethane. The organic phase was dried over Na2SO4, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography (petroleum/dichloromethane=1/3) to give compound 5 (1.86 g, 88.9percent) as yellow solid. Mp: 73 °C. MS(EI): m/z=238 (M+). 1H NMR (CDCl3, 400 M Hz) δ/ppm: 9.92 (s, 1H), 7.73 (d, H), 7.43 (d, 1H), 1.34 (s, 12H).
Reference: [1] Tetrahedron, 2012, vol. 68, # 44, p. 9113 - 9118
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