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Product Details of [ 59-67-6 ]

CAS No. :59-67-6 MDL No. :MFCD00006391
Formula : C6H5NO2 Boiling Point : -
Linear Structure Formula :- InChI Key :PVNIIMVLHYAWGP-UHFFFAOYSA-N
M.W : 123.11 Pubchem ID :938
Synonyms :
Nicotinic acid;Vitamin B3;NSC 169454
Chemical Name :Nicotinic acid

Calculated chemistry of [ 59-67-6 ]

Physicochemical Properties

Num. heavy atoms : 9
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.0
Num. rotatable bonds : 1
Num. H-bond acceptors : 3.0
Num. H-bond donors : 1.0
Molar Refractivity : 31.2
TPSA : 50.19 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.8 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.86
Log Po/w (XLOGP3) : 0.36
Log Po/w (WLOGP) : 0.78
Log Po/w (MLOGP) : -1.13
Log Po/w (SILICOS-IT) : 0.75
Consensus Log Po/w : 0.32

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.56

Water Solubility

Log S (ESOL) : -1.26
Solubility : 6.81 mg/ml ; 0.0553 mol/l
Class : Very soluble
Log S (Ali) : -0.98
Solubility : 12.9 mg/ml ; 0.105 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -1.35
Solubility : 5.46 mg/ml ; 0.0444 mol/l
Class : Soluble

Medicinal Chemistry

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

Safety of [ 59-67-6 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P264-P273-P280-P305+P351+P338-P337+P313-P501 UN#:N/A
Hazard Statements:H319-H413 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 59-67-6 ]

* 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 [ 59-67-6 ]
  • Downstream synthetic route of [ 59-67-6 ]

[ 59-67-6 ] Synthesis Path-Upstream   1~64

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Reference: [1] Patent: WO2015/97122, 2015, A1,
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[13] Biochemical Journal, 1953, vol. 53, p. 474,476
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  • 4
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  • [ 1120-90-7 ]
YieldReaction ConditionsOperation in experiment
65% With N-iodo-succinimide; [4,4’-bis(tert-butyl)-2,2’-bipyridine]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl]phenyl]iridium(III) hexafluorophosphate; iodine; caesium carbonate In acetonitrile at 50℃; for 24 h; Inert atmosphere; Irradiation; Sealed tube General procedure: To a 15 mL test tube with septum Cs2CO3 (0.6 mmol, 195 mg), aromaticcarboxylic acid (1) (0.3 mmol), [Ir(dF(CF3)ppy)2dtbbpy]PF6 (D) (6 μmmol, 6.7 mg), NIS (1.5mmol, 337.5 mg) and I2 (60 μmol, 20 molpercent) were added. The tube was evacuated and backfilledwith argon for three times, and then 3 mL of dry CH3CN was added through a syringer underargon. The tube was sealed with Parafilm M® and placed in an oil bath with a contact thermometer,and the reaction was carried out at 50 °C under irradiation with 6 × 5 W blue LEDs (λmax = 455nm). After 24 h, the resulting mixture was filtered through a 2 cm thick pad of silica, and the silicawas washed with DCM) (50 mL). The filtrate was collected and the solvent was removed in vacuo.The crude residue was purified by silica gel flash column chromatography to provide the targetproduct (2). (Note: The reaction was very sensitive to moisture, and the yields sharply decreased to less than 5percent when 0.01 equivalent of H2O was added to the reaction system).
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  • 8
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  • 13
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  • 14
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Reference: [1] Patent: WO2013/48811, 2013, A1, . Location in patent: Page/Page column 28
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[2] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2010, vol. 49, # 4, p. 526 - 531
[3] Phosphorus, Sulfur and Silicon and the Related Elements, 2006, vol. 181, # 9, p. 2079 - 2087
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[6] Journal of the Chemical Society, 1953, p. 1358,1361
[7] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 1, p. 184 - 187
[8] Journal of Heterocyclic Chemistry, 2010, vol. 47, # 5, p. 1225 - 1229
[9] European Journal of Medicinal Chemistry, 2010, vol. 45, # 11, p. 4963 - 4967
[10] Organic and Biomolecular Chemistry, 2012, vol. 10, # 9, p. 1785 - 1794
[11] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 6, p. 2158 - 2171
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[14] Chemical Communications (Cambridge, United Kingdom), 2012, vol. 48, # 92, p. 11307 - 11309,3
[15] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 8, p. 2286 - 2297
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[17] European Journal of Medicinal Chemistry, 2014, vol. 71, p. 199 - 218
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[19] Tetrahedron, 2014, vol. 70, # 12, p. 2190 - 2194
[20] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2013, vol. 52, # 10, p. 1318 - 1324
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[23] Archiv der Pharmazie, 2014, vol. 347, # 8, p. 576 - 588
[24] Russian Journal of General Chemistry, 2015, vol. 85, # 3, p. 746 - 751
[25] Medicinal Chemistry Research, 2014, vol. 24, # 6, p. 2514 - 2528
[26] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 13, p. 3397 - 3407
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  • 17
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  • [ 101012-32-2 ]
Reference: [1] Chinese Chemical Letters, 2011, vol. 22, # 9, p. 1009 - 1012
  • 18
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[2] Journal of the American Chemical Society, 1946, vol. 68, p. 907
  • 19
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  • 20
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  • 21
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Reference: [1] Patent: US5125956, 1992, A,
  • 22
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  • 24
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  • [ 141-43-5 ]
  • [ 6265-73-2 ]
YieldReaction ConditionsOperation in experiment
86%
Stage #1: With thionyl chloride In toluene at 140℃; for 4 h;
Stage #2: at 50℃;
Example 4; Preparation of (R)-4-trimethyIammonium-3-(tetradecylcarbamoyl)-amino- butyrate of {2[-(N-methyl-(1 ,4-dihydro-pyridine)-3-yl)carbonyl]-amino}ethyliodide (ST3496); Preparation of the intermediate N-(2-hvdroxy-ethvD-nicotinamide; SOCb (455 μl, 6.26 mmol) ) was added to a suspension of nicotinic acid (0.385 g, 3.13 mmol) in anhydrous toluene (15 ml) and the reaction mixture was refluxed at 1400C for 4 hours. Then the clear solution was cooled and the solvent was removed under vacuum. The solid residue was washed three times with diethyl ether and fresh anhydrous toluene (15 ml) and ethanolamine (756 μl, 12.52 mmol) were added. The mixture was warmed up to 500C overnight. EPO <DP n="18"/>Then the solvent was removed under vacuum and the solid residue was purified by silica gel chromatography using as eluent dichloromethane/methanol 9.2/0.8. The desired product was obtained as a white solid (450 mg, 86percent yield), m.p. = 84.5-85.50C; 1H NMR (300MHz, DMSOd6) δ: 9.00 (s, 1H, NH), 8.68, (m, 2H, Ar), 8.17 (d, 1H, Ar), 7.60 (m, 1H1 Ar), 4.74 (m, 1H, OH), 3.51 (m, 2H, CH2), 3.36 (m, 2H1 CH2).
77% With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0℃; for 24 h; General procedure: To obtain the alcohol derivatives, an esterification or amidation with the corresponding benzoic acid (1equiv) was carried out in 20mL anhydrous CH2Cl2 at 0°C using the corresponding alcohol or amine (1.0equiv), EDC·HCl (1.5equiv), and DMAP or HOBt (0.2equiv). After the reaction was completed (TLC control) a subsequent purification by flash-chromatography was performed to obtain compounds 10q-u
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[2] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 21, p. 5134 - 5147
[3] Archiv der Pharmazie, 2003, vol. 336, # 10, p. 445 - 455
  • 25
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  • [ 6265-73-2 ]
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Reference: [1] Chemical and Pharmaceutical Bulletin, 1984, vol. 32, # 3, p. 1063 - 1070
  • 27
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  • [ 71-36-3 ]
  • [ 6938-06-3 ]
YieldReaction ConditionsOperation in experiment
80% With sulfuric acid In benzene for 8 h; Reflux General procedure: To the solution of n-butyl alcohol (110 mL) andbenzene (30 mL) which contained compounds of I(0.2 mol), concentrated sulfuric acid (98percent, d = 1.84)was added and stirred. The mixture was heated toreflux with a water separator and stirred for 8 hours,then the excess n-butyl alcohol and benzene wasdistillated out, the residuum was pour into ice water(150 mL) and neutralized to pH = 7–8 with saturatedsodium carbonate solution. The water solution wasextracted with isopropyl ether (3 × 100 mL). Thecombined extract solution was dried overnight byanhydrous magnesium sulfate and filtered. The filtratewas distillated out first the isopropyl ether thendistillated out the ester of II under vacuum.
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[9] Patent: US2012/291737, 2012, A1,
[10] Patent: US2012/291737, 2012, A1,
[11] Patent: US2012/291737, 2012, A1,
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YieldReaction ConditionsOperation in experiment
84.3% With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 60℃; for 20 h; Niacin (purchased from Beijing coupling technology Co., Ltd., purity >98percent) (0.85g, 7mmol) was dissolved in 30mL N, N-dimethylformamide solution,Add EDCI hydrochloride (1.41 g, 7 mmol) and tryptamine (1.12 g, 7 mmol), and react at 60 ° C for 20 h.Finally, 1.34 g of CD19 pure product (yield 84.3percent) was obtained.
72% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; General procedure: To a solution of the corresponding pyridine acids (3a, 3b, 3d and3e) (0.5 mmol), triethylamine (1.2 mmol), HOBT (0.6 mmol) andEDCI (0.6 mmol) in CH2Cl2 (8 mL) was added the appropriatedtryptamines (1 or 2) (0.5 mmol). The reaction mixturewas stirred atroom temperature overnight, and CH2Cl2 was then evaporated todryness under reduced pressure. The residue was dissolved inEtOAc (10 mL) and consecutively washed with a 10percent aqueousNaHCO3 solution (3 10 mL) and H2O (10 mL). The organic phasewas dried over sodium sulfate and evaporated to dryness underreduced pressure. The residue was purified on a silica gel columnusing mixtures of CH2Cl2/MeOH as eluent, obtaining the correspondingintermediate 4aee as a pure solid. 4.1.1.1
N-(2-(1H-indol-3-yl)ethyl)nicotinamide (4a)
White solid; yield 72percent; 1H NMR (500 MHz, DMSO-d6) δ 10.84 (s, 1H), 9.02 (d, J = 1.3 Hz, 1H), 8.82 (t, J = 5.0 Hz, 1H), 8.72 (dd, J = 4.6, 1.3 Hz, 1H), 8.20 (d, J = 7.9 Hz, 1H), 7.60 (d, J = 7.8 Hz, 1H), 7.52 (dd, J = 7.6, 5.1 Hz, 1H), 7.37 (d, J = 8.1 Hz, 1H), 7.21 (s, 1H), 7.09 (t, J = 7.5 Hz, 1H), 7.00 (t, J = 7.4 Hz, 1H), 3.59 (dd, J = 13.6, 6.9 Hz, 2H), 3.00 (t, J = 7.4 Hz, 2H).
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  • 46
  • [ 31637-97-5 ]
  • [ 59-67-6 ]
  • [ 3612-80-4 ]
  • [ 882-09-7 ]
  • [ 31637-96-4 ]
Reference: [1] Journal of Pharmaceutical Sciences, 1985, vol. 74, # 3, p. 295 - 299
  • 47
  • [ 1313480-49-7 ]
  • [ 59-67-6 ]
  • [ 3612-80-4 ]
  • [ 25812-30-0 ]
  • [ 1313404-96-4 ]
  • [ 107-21-1 ]
Reference: [1] European Journal of Pharmaceutical Sciences, 2011, vol. 43, # 3, p. 99 - 108
  • 48
  • [ 59-67-6 ]
  • [ 20260-53-1 ]
YieldReaction ConditionsOperation in experiment
96% With thionyl chloride In N,N-dimethyl-formamide at 0 - 78℃; for 3 h; Reflux Under the anhydrous condition, nicotinic acid (8.12 mmol) and 2 drops of dry DMF were added into the vigorously stirred SOCl2 (10 mL) at 0 °C. The reaction mixture was heated to 78 °C to reflux for 3 h to yield the yellow solid after the excess SOCl2 was evaporated under reduced pressure. Then 10 mL diethyl ether was added to reflux for 1 h, and then filtered to obtain the white solid nicotinoyl chloride hydrochloride 1.388 g (yield: 96.0percent).
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[2] Journal of Organic Chemistry, 2009, vol. 74, # 17, p. 6691 - 6702
[3] Green Chemistry, 2009, vol. 11, # 1, p. 83 - 90
[4] Molecules, 2014, vol. 19, # 4, p. 4791 - 4801
[5] Phosphorus, Sulfur and Silicon and the Related Elements, 2011, vol. 186, # 3, p. 552 - 557
[6] Zhurnal Obshchei Khimii, 1946, vol. 16, p. 1033,1035[7] Chem.Abstr., 1947, p. 2737
[8] Chemische Berichte, 1926, vol. 59, p. 1479,1482
[9] Journal of Organic Chemistry, 1982, vol. 47, # 13, p. 2633 - 2637
[10] Journal of the American Chemical Society, 1985, vol. 107, # 17, p. 4904 - 4911
[11] Journal of Organic Chemistry, 1981, vol. 46, # 22, p. 4439 - 4445
[12] Phosphorus and Sulfur and the Related Elements, 1981, vol. 11, p. 33 - 46
[13] Tetrahedron Asymmetry, 2003, vol. 14, # 12, p. 1691 - 1699
[14] Patent: WO2004/76450, 2004, A1, . Location in patent: Page 126
[15] Patent: US2006/20135, 2006, A1, . Location in patent: Page/Page column 7; 8-9
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[17] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 24, p. 7250 - 7254
[18] Chemistry of Natural Compounds, 2012, vol. 48, # 2, p. 189 - 193
[19] Crystal Growth and Design, 2012, vol. 12, # 12, p. 6012 - 6022
[20] Patent: EP2548864, 2013, A1, . Location in patent: Paragraph 0360
[21] Patent: WO2013/14104, 2013, A1, . Location in patent: Page/Page column 48; 49
[22] Patent: WO2013/14102, 2013, A1, . Location in patent: Page/Page column 75
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[27] Patent: US3953596, 1976, A,
  • 49
  • [ 59-67-6 ]
  • [ 20260-53-1 ]
Reference: [1] Patent: US4540564, 1985, A,
[2] Patent: US4824850, 1989, A,
[3] Patent: US4617298, 1986, A,
[4] Patent: US4863911, 1989, A,
  • 50
  • [ 59-67-6 ]
  • [ 20260-53-1 ]
Reference: [1] Patent: US5385897, 1995, A,
  • 51
  • [ 59-67-6 ]
  • [ 89895-55-6 ]
Reference: [1] Tetrahedron Asymmetry, 2007, vol. 18, # 2, p. 181 - 191
  • 52
  • [ 59-67-6 ]
  • [ 69045-84-7 ]
Reference: [1] Patent: WO2014/198278, 2014, A1,
[2] Patent: WO2014/198278, 2014, A1,
[3] Patent: WO2014/198278, 2014, A1,
[4] Patent: WO2014/198278, 2014, A1,
[5] Patent: WO2014/198278, 2014, A1,
[6] Patent: WO2014/198278, 2014, A1,
[7] Patent: WO2014/198278, 2014, A1,
[8] Patent: WO2014/198278, 2014, A1,
[9] Patent: WO2014/198278, 2014, A1,
[10] Patent: WO2014/198278, 2014, A1,
[11] Patent: WO2014/198278, 2014, A1,
[12] Patent: WO2014/198278, 2014, A1,
[13] Patent: WO2014/198278, 2014, A1,
  • 53
  • [ 59-67-6 ]
  • [ 79456-26-1 ]
Reference: [1] Patent: WO2014/198278, 2014, A1,
[2] Patent: WO2014/198278, 2014, A1,
[3] Patent: WO2014/198278, 2014, A1,
[4] Patent: WO2014/198278, 2014, A1,
[5] Patent: WO2014/198278, 2014, A1,
[6] Patent: WO2014/198278, 2014, A1,
[7] Patent: WO2014/198278, 2014, A1,
[8] Patent: WO2014/198278, 2014, A1,
[9] Patent: WO2014/198278, 2014, A1,
[10] Patent: WO2014/198278, 2014, A1,
[11] Patent: WO2014/198278, 2014, A1,
[12] Patent: WO2014/198278, 2014, A1,
[13] Patent: WO2014/198278, 2014, A1,
  • 54
  • [ 59-67-6 ]
  • [ 69045-83-6 ]
YieldReaction ConditionsOperation in experiment
75% at 120 - 180℃; Autoclave EXAMPLE 10 Conversion of Nicotinic acid to 2,3-dichloro-5-(trichloromethyl)pyridine. Nicotinic acid (50 g, 0.4 mole) and phosphorous trichloride (223 g, 1.6 mole) were added to an 0.5 L jacketed autoclave, connected to a cooling- heating circulator. The temperature of the reaction mixture was adjusted to 120 °C and chlorine gas (115 g, 1.6 mole) was added to head space from a pressure bottle. During addition of chlorine was the temperature maintained between 120 °C and 140 °C with cooling circulation on the jacket. After addition of chlorine gas is the pressure in the autoclave around 3 bar. The temperature is increased to 180 °C (will be preferred to increase to 210 °C, but this was not possible in the current setup) and kept there for 144 hours (210 °C will finish reaction in 16 hours). During the reaction HCl(g) was removed through a scrubber periodically to keep pressure between 12 and 16 bar. The autoclave was then cooled to 25 °C and ventilated to a Caustic Lye scrubber. The resulting solution was heated to reflux to recover phosphorous trichloride by distillation. The autoclave was closed again and chlorine gas (50 g, 0.5 mole) was added at room temperature. The resulting mixture was heated to 130 °C and pressure was kept below 15 bar by removing HCl(g) above a condenser to a caustic lye scrubber. When pressure becomes stable (typically after 2 - 4 hours), the reaction is considered completed and the autoclave cooled down. If analysis shows otherwise, the final chlorination procedure can be repeated. The reaction mixture was then transferred to a round bottomed flask and phosphoryl chloride was removed by distillation. In case there is any solid PC15 in the reactor, it can be converted to phosphoryl chloride with a few drops of water and transferred together with the main reaction mixture. Upon distillation of phosphoryl chloride - the crude product was obtained by addition to ice cold water, stirred for 10 minutes and allowed to stand for separation for 1 hours at 25 °C. The lower organic phase is separated from the acidic water phase and the product hereafter distilled to give 80 g of 2,3-dichloro-5-(trichloromethyl)pyridine with a purity of 96percent (75percent yield).
Reference: [1] Patent: WO2014/198278, 2014, A1, . Location in patent: Page/Page column 16; 17
[2] Patent: WO2014/198278, 2014, A1,
[3] Patent: WO2014/198278, 2014, A1,
[4] Patent: WO2014/198278, 2014, A1,
[5] Patent: WO2014/198278, 2014, A1,
[6] Patent: WO2014/198278, 2014, A1,
  • 55
  • [ 59-67-6 ]
  • [ 69045-78-9 ]
  • [ 69045-83-6 ]
YieldReaction ConditionsOperation in experiment
33 %Chromat. at 210℃; for 14 h; Autoclave EXAMPLE 7 Conversion of Nicotinic acid to a mixture of 2-chloro-5- (trichloromethyl)pyridine and 2,3-dichloro-5-(trichloromethyl)pyridine. To a 250 ml Berghof autoclave with PTFE lining was added Nicotinic acid (20g, 162 mmole) and phosphorous pentachloride (139 g, 668 mmole). The autoclave was closed and heated to 210 °C for 14 hours. During the heating an exotherm was observed around a temperature of 130 °C bringing the temperature to 190 °C and a pressure increase from 2 bar to 8 bar within 2 minutes. The heating was continued to 210 °C. After the 14 hours the pressure had increased to 37 Bar. The autoclave was cooled to room temperature, ventilated to a scrubber, opened and quantified by GC indicating a yield of 2- chloro-5-(trichloromethyl)pyridine of 33percent compared to the Nicotinic acid starting material and a yield of 2,3-dichloro-5-(trichloromethyl)pyridine 60percent.
Reference: [1] Patent: WO2014/198278, 2014, A1,
[2] Patent: WO2014/198278, 2014, A1,
[3] Patent: WO2014/198278, 2014, A1, . Location in patent: Page/Page column 14
[4] Patent: WO2014/198278, 2014, A1,
  • 56
  • [ 59-67-6 ]
  • [ 3099-50-1 ]
  • [ 69045-78-9 ]
  • [ 69045-83-6 ]
Reference: [1] Patent: WO2014/198278, 2014, A1, . Location in patent: Page/Page column 13
  • 57
  • [ 59-67-6 ]
  • [ 69045-78-9 ]
  • [ 69045-83-6 ]
Reference: [1] Patent: WO2014/198278, 2014, A1, . Location in patent: Page/Page column 13; 14
  • 58
  • [ 59-67-6 ]
  • [ 3099-50-1 ]
  • [ 69045-78-9 ]
  • [ 69045-83-6 ]
Reference: [1] Patent: WO2014/198278, 2014, A1, . Location in patent: Page/Page column 13
  • 59
  • [ 59-67-6 ]
  • [ 78-90-0 ]
  • [ 79455-30-4 ]
Reference: [1] Patent: EP376185, 1994, B1,
  • 60
  • [ 59-67-6 ]
  • [ 329214-79-1 ]
Reference: [1] Journal of the American Chemical Society, 2017, vol. 139, # 22, p. 7440 - 7443
[2] Organic Letters, 2017, vol. 19, # 16, p. 4291 - 4294
  • 61
  • [ 59-67-6 ]
  • [ 148763-41-1 ]
Reference: [1] Tetrahedron Asymmetry, 2007, vol. 18, # 2, p. 181 - 191
  • 62
  • [ 59-67-6 ]
  • [ 75-98-9 ]
  • [ 832715-99-8 ]
Reference: [1] Patent: WO2008/33858, 2008, A2, . Location in patent: Page/Page column 206
[2] Patent: WO2014/64131, 2014, A2, . Location in patent: Page/Page column 104; 105
[3] Patent: WO2008/33858, 2008, A2, . Location in patent: Page/Page column 206
  • 63
  • [ 59-67-6 ]
  • [ 815-17-8 ]
  • [ 832715-99-8 ]
YieldReaction ConditionsOperation in experiment
4%
Stage #1: With sulfuric acid In water at 20℃; for 0.166667 h; Inert atmosphere
Stage #2: at 90℃; for 2 h; Inert atmosphere
Step 1: Preparation of 6-tert-butylnicotinic acid To a suspension of nicotinic acid (2.00 g, 16.2 mmol) in water (250mL) was added concentrated sulfuric acid (1 mL, 18.8 mmol) and the mixture stirred under nitrogen to form a clear solution. Pivalic acid (1.83 g, 17.9 mmol) was added and stirring under nitrogen at ambient temperaturecontinued for 10 minutes. Silver nitrate (125 mg, 0.74 mmol) was added followed by ammonium persulfate (295 mg, 1.3 mmol), the flask wrapped in aluminum foil to exclude light and the mixture heated to 90 °C under nitrogen. After 2 hours the reaction mixture was cooled to ambient temperature and the aqueous mixture concentrated in vacuo to a colorless solid. The solid was triturated with tetrahydrofuran and filtered. The solid residue was retriturated withmethanol and filtered. Both filtrates were combined and concentrated in vacuo. The crude product was purified by reverse phase chromatography using a 85 g c-i 8 column gradient eluted from 10percent acetonitrile in water to 100percent acetonitrile. The product containing fractions were combined and concentrated in vacuo. The residue was lyophilized from water to give 6-tert- butylnicotinic acid as a colorless solid (139 mg, 4 percent).Lc/MS: m/z calculated for c10H13No2 ([M+Hjj: 180.2. Found: 180.1 (positive mode electrospray ionization).
Reference: [1] Patent: WO2014/90715, 2014, A1, . Location in patent: Page/Page column 45
  • 64
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  • [ 884049-52-9 ]
Reference: [1] Chinese Chemical Letters, 2011, vol. 22, # 9, p. 1009 - 1012
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