Home Cart 0 Sign in  

[ CAS No. 874-24-8 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 874-24-8
Chemical Structure| 874-24-8
Structure of 874-24-8 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

* Shipping: {[proInfo.prShipping]}

Quality Control of [ 874-24-8 ]

Related Doc. of [ 874-24-8 ]

Alternatived Products of [ 874-24-8 ]
Product Citations

Product Details of [ 874-24-8 ]

CAS No. :874-24-8 MDL No. :MFCD00006294
Formula : C6H5NO3 Boiling Point : -
Linear Structure Formula :- InChI Key :BRARRAHGNDUELT-UHFFFAOYSA-N
M.W : 139.11 Pubchem ID :13401
Synonyms :
3-hydroxypyridine-2-carboxylic acid;3-HPA;HPicOH

Calculated chemistry of [ 874-24-8 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 10
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.0
Num. rotatable bonds : 1
Num. H-bond acceptors : 4.0
Num. H-bond donors : 2.0
Molar Refractivity : 33.22
TPSA : 70.42 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.23 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.61
Log Po/w (XLOGP3) : 1.3
Log Po/w (WLOGP) : 0.49
Log Po/w (MLOGP) : -1.72
Log Po/w (SILICOS-IT) : 0.27
Consensus Log Po/w : 0.19

Druglikeness

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

Water Solubility

Log S (ESOL) : -1.9
Solubility : 1.75 mg/ml ; 0.0126 mol/l
Class : Very soluble
Log S (Ali) : -2.38
Solubility : 0.581 mg/ml ; 0.00418 mol/l
Class : Soluble
Log S (SILICOS-IT) : -0.8
Solubility : 22.3 mg/ml ; 0.16 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.28

Safety of [ 874-24-8 ]

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 [ 874-24-8 ]

* 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 [ 874-24-8 ]
  • Downstream synthetic route of [ 874-24-8 ]

[ 874-24-8 ] Synthesis Path-Upstream   1~30

  • 1
  • [ 874-24-8 ]
  • [ 16867-03-1 ]
Reference: [1] Patent: US4022897, 1977, A,
  • 2
  • [ 98140-94-4 ]
  • [ 874-24-8 ]
  • [ 655244-89-6 ]
Reference: [1] Journal of Organic Chemistry, 2004, vol. 69, # 1, p. 54 - 61
  • 3
  • [ 76045-30-2 ]
  • [ 874-24-8 ]
  • [ 239101-34-9 ]
Reference: [1] Journal of Medicinal Chemistry, 1999, vol. 42, # 13, p. 2432 - 2440
  • 4
  • [ 27507-15-9 ]
  • [ 874-24-8 ]
Reference: [1] Journal of Organic Chemistry, 2004, vol. 69, # 1, p. 54 - 61
  • 5
  • [ 1462-86-8 ]
  • [ 874-24-8 ]
Reference: [1] Journal of Organic Chemistry, 2004, vol. 69, # 1, p. 54 - 61
  • 6
  • [ 1121-60-4 ]
  • [ 874-24-8 ]
Reference: [1] Croatica Chemica Acta, 2010, vol. 83, # 3, p. 291 - 298
  • 7
  • [ 98-98-6 ]
  • [ 874-24-8 ]
Reference: [1] Heterocyclic Communications, 2003, vol. 9, # 5, p. 489 - 492
[2] Polish Journal of Chemistry, 2005, vol. 79, # 11, p. 1813 - 1819
[3] Croatica Chemica Acta, 2010, vol. 83, # 3, p. 291 - 298
  • 8
  • [ 1849-55-4 ]
  • [ 874-24-8 ]
Reference: [1] Chemische Berichte, 1957, vol. 90, p. 758,761
  • 9
  • [ 1121-25-1 ]
  • [ 874-24-8 ]
Reference: [1] Chemische Berichte, 1957, vol. 90, p. 758,761
  • 10
  • [ 67-56-1 ]
  • [ 874-24-8 ]
  • [ 62733-99-7 ]
YieldReaction ConditionsOperation in experiment
99% at 0℃; for 6 h; Reflux To a suspension of 3-hydroxypicolinic acid 1 (10 g, 72 mmol, 1equiv) in methanol (150 mL, 0.5 M) was added dropwise at 0 °C aconcentrated sulfuric acid (12 mL, 216 mmol, 3 equiv.). The obtainedsolution was stirred at reflux 6 h. The cooled reaction mixture wasconcentrated under reduced pressure. The pH was adjusted at 8.5 withan aqueous solution of saturated NaHCO3 and solid NaHCO3. Theaqueous layer was extracted with EtOAc and the combined organiclayer was washed with brine, dried over MgSO4 and concentrated underreduced pressure to give 2 as a white solid (10.9 g, 99percent). Rf=0.3(Petroleum ether/EtOAc 1/1, v/v). m.p. = 74 °C. 1H NMR (300 MHz,CDCl3): δ (ppm)=4.06 (s, 3H), 7.34 (dd, J=3.9, 8.4 Hz, 1H), 7.38(dd, J=1.5, 8.4 Hz, 1H), 8.38 (dd, J=1.5, 3.9 Hz, 1H), 10.64 (s, 1H).13C NMR (75 MHz, CDCl3): δ=53.2, 126.3, 129.8, 130.2, 141.6, 158.9,169.9. MS (ESI+): m/z (percent): 154 (100) [M+H]+.
93.1% for 24 h; Inert atmosphere; Reflux To a stirred mixture of 3-thydroxypicolinic acid (10 g, 71.9 mmol) in 350 mL CH3OH and 5 mL H2SO4 was added several drops benzene as dehydrate; the resulting mixture was refluxed for another 24 h under the protection of nitrogen. After cooled to room temperature (rt), the mixture was poured into brine and extracted with ethyl acetate (EA). The organic layer was washed with brine for three times and then dried over anhydrous Na2SO4. After removal of the solvent, the intermediate (2) was gained as a white solid (11.0 g, 93.1percent). 1H NMR (CDCl3, 400 MHz), δ (ppm): 7.68-7.62 (m, 2H), 7.52-7.50 (d, J=7.92 Hz, 2H), 7.45-7.43 (d, J=7.92 Hz, 2H), 4.28-4.25 (t, J=12.4 Hz, 2H), 3.94 (s, 3H), 1.94-1.89 (m, 4H), 1.62-1.57 (m, 2H), 1.25-1.04 (m, 14H), 0.84-0.81 (t, J=11.8 Hz, 3H), 0.59-0.58 (m, 4H).
85% at 83℃; To a solution of compound 20A (100.0 g, 0.719 mol, 1.0 eq) in methanol (1.5 L) was added cone, sulfuric acid (120 mL, 2.157 mol, 3.0 eq) and the reaction mixture was heated to reflux (83 °C) overnight. The solvent was removed in vacuo, and the residue was diluted with water (1.5 L), and adjusted to pH 8.5 with solid K2CO3, then extracted with DCM (3 x 1 L). The organic phases were dried over sodium sulfate and concentrated under reduced pressure to give compound 20B (94 g, 85percent) as a slightly blue solid. JH NMR (400 MHz, CDCI3) δ 10.61 (s, 1H), 8.28 (dd, / = 4.1, 1.4 Hz, 1H), 7.42 (dd, / = 8.5, 4.2 Hz, 1H), 7.37 (dd, / = 8.5, 1.5 Hz, 1H), 4.05 (s, 3H)
83% at 0℃; for 24 h; Reflux 3-Hydroxypicolinic acid (5.0 g, 35.94 mmol) was dissolved in methanol (120 mL).
To the resulting solution was slowly added dropwise sulfuric acid (5.75 mL, 107.83 mmol) at 0 °C and the solution was refluxed with heat for 24 hrs, cooled to room temperature, and evaporated under reduced pressure.
The resulting residue was diluted with dichloromethane and distilled water, neutralized with 6N sodium hydroxide, and extracted with dichloromethane.
The organic solvent was dried over anhydrous magnesium sulfate (MgSO4) to concentrate.
The resulting residue was isolated and purified by silica gel column chromatography (hexane/ethylacetate = 1/1) to give the white title compound (4.62 g, 83 percent).
1H NMR (600 MHz, CDCl3) δ 8.28 (dd, J = 1.2, 2.4 Hz, 1H), 7.43 (dd, J = 4.2, 4.2 Hz, 1H), 7.38, (dd, J = 1.2, 7.2 Hz, 1H), 4.06 (s, 3H).
82.8% at 80℃; A solution of 3-hydroxypicolinic acid (30 g, 0.22 mol) in CH3OH (300 mL) was stirred at RT and cone. H2S04 (30 mL) was added dropwise. The resulting mixture was stirred at 80 °C overnight. After the pH was adjusted to 7 with solid Na2C03, the mixture was filtrated and the precipitate was thoroughly washed with EtOAc several times. The filtrate was concentrated to give crude methyl 3-hydroxypicolinate (27 g, yield: 82.8 percent). 1H- MR (CDC13, 400 MHz) δ 10.57 (s, 1H), 8.22-8.20 (m, 1H), 7.32-7.29 (m, 1H), 3.93 (s, 3H). MS (M+H)+: 154.
80%
Stage #1: for 24 h; Reflux
Stage #2: With potassium carbonate In water
H2SO4 (1.8 mL, 3 equiv) was added dropwise to a suspension of 3-hydroxypicolinic acid 7 (1.5 g, 10.5 mmol) in MeOH (24 mL). The mixture was refluxed for 24 h. Then, the mixture was basified with a solution of K2CO3 (pH 8.5). The aqueous layer was extracted with EtOAc, and the organic layer was dried over MgSO4 and concentrated under reduced pressure to give desired methyl ester 8 (1.28 g, 80percent) as a white solid. 1H and 13C NMR data were in agreement with those given in the literature.refPreviewPlaceHolder18 L. Louise-Leriche, E. Punescu, G. Saint-Andre, R. Baati, A. Romieu, A. Wagner and P.-Y. Renard. Chem.-Eur. J., 16 (2010), pp. 3510-3523. 18
79% for 18 h; Reflux A mixture of 3-hydroxypicolinic acid (2 g, 14.1 mmol) in MeOH (100 mL) containing concentrated H2SO4 (4 mL) was refluxed for 18 h. The mixture was concentrated to about 40 mL, diluted with water (150 mL), adjusted to pH around 6 with Na2CO3, and then extracted with CHCl3 (100 mL.x.3). The combined organic extracts were washed with water, brine and dried over Na2SO4, filtered, and the filtrate was concentrated to give 1.71 g (79percent) of methyl 3-hydroxy-2-pyridinecarboxylate as off-white crystals. 1H NMR (400 MHz, CDCl3): δ 10.63 (s, 1H), 8.30-8.25 (m, 1H), 7.50-7.35 (m, 2H), 4.06 (s, 3H); LRMS (ESI), m/z 154 (M+H).
65% With sulfuric acid; water In benzene for 24 h; Inert atmosphere; Reflux In 500mL single-neck flask fitted with a water separator, were added sequentially 4. 17g namely 0. 03mol 3-hydroxy-2-pyridine carboxylic acid, 350mL of anhydrous methanol, and then slowly added dropwise 6mL of concentrated sulfuric acid and 10mL benzene, under a nitrogen blanket reflux 24h. The reaction was stopped, cooled to room temperature, spin most methanol, with sodium hydroxide solution 2mol / L pH is adjusted to 4. 0~5. 0, extracted three times with 30mL dichloromethane and the combined organic phase was dried over anhydrous magnesium dried overnight, filtered, and the solvent under reduced pressure to spin, to give an off-white solid was dried in vacuo to give product 3. 0g, 65percent yield
64%
Stage #1: for 120 h; Heating / reflux
Stage #2: With potassium carbonate In methanol; water
Reference Example 3; 4- (6-formγl-5-methoxγpγridin-2-γl) benzonitrile; (step 1); A solution of 3-hydroxypicolinic acid (50.9 g) and cone, sulfuric acid (40 iαL) in methanol (500 mL) was heated under reflux for 5 days. The reaction mixture was concentrated under reduced pressure, and the residue was poured into cold water. The mixture was basified with potassium carbonate, and extracted twice with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (solvent gradient; 0-50percent ethyl acetate/hexane) and crystallized from ethyl acetate/hexane to give methyl 3-hydroxypyridine-2- carboxylate (35.5 g, 64percent) as white crystals.
45% for 6 h; Heating / reflux A mixture of 3-hydroxypicolic acid (1.39 g, 10.0 mmol) and HCl (2 M in methanol, 60 ml) was refluxed for 6 hours. The solvent was removed under reduced pressure and the residue was neutralized with saturated aqueous NaHCO3 solution, extracted with ethyl acetate, dried (MgSO4) and evaporated under reduced pressure to give methyl 3- hydroxypicolinate (687 mg, 45 percent, colorless solid).
32% at 64℃; for 24 h; In a 500 ml_ round-bottorned flask fitted with a condenser-and a magnetic stirrer were placed MeOH (250 mL), S-hydroxypyridine^-carboxylic acid 1 (10.0 g, 72 mmol) and concentrated H^SO4 (3 mL). The reaction mix was heated to 64°C for 24 hours. The reaction mix was cooled to room temperature. The solvent was removed under reduced pressure; the residue was partitioned between ethyl acetate (150 mL) and water (20 mL). Solid sodium carbonate was added to adjust the pH to 6. The organic layer was separated, dried over Na2SO4, and concentrated to give crude 3.5 g of intermediate 2 (32percent yield).
23% Inert atmosphere; Reflux 3-hydroxy picolinic acid (1.0 g, 7.19 mmol) in methanol (15 ml) solution was added dropwise concentrated sulfuric acid (200 μl). Under an argon atmosphere, and stirred under reflux conditions overnight. After completion of the reaction, concentrated to dryness. Saturated saline, a saturated aqueous solution of sodium hydrogen carbonate was added, and the mixture was extracted with chloroform. Dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. To give the title compound (250 mg, 23percent).

Reference: [1] Journal of Controlled Release, 2018, vol. 290, p. 102 - 111
[2] Tetrahedron, 2011, vol. 67, # 11, p. 2118 - 2124
[3] Patent: WO2018/5662, 2018, A1, . Location in patent: Paragraph 0290
[4] Patent: EP3255042, 2017, A2, . Location in patent: Paragraph 0180; 0181
[5] Patent: WO2014/121418, 2014, A1, . Location in patent: Page/Page column 44
[6] ChemMedChem, 2016, vol. 11, # 23, p. 2607 - 2620
[7] Chemical Communications, 2011, vol. 47, # 18, p. 5295 - 5297
[8] Tetrahedron, 2011, vol. 67, # 45, p. 8757 - 8762
[9] Chemical Communications, 2014, vol. 50, # 30, p. 3947 - 3950
[10] Patent: US2010/29650, 2010, A1, . Location in patent: Page/Page column 65
[11] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 22, p. 6705 - 6708
[12] Journal of Heterocyclic Chemistry, 2001, vol. 38, # 5, p. 1153 - 1166
[13] Pesticide Science, 1997, vol. 50, # 4, p. 275 - 282
[14] Tetrahedron Letters, 1996, vol. 37, # 4, p. 459 - 462
[15] Patent: CN105294781, 2016, A, . Location in patent: Paragraph 0073; 0075; 0076
[16] Patent: WO2007/89031, 2007, A1, . Location in patent: Page/Page column 83-84
[17] Chemistry - A European Journal, 2010, vol. 16, # 11, p. 3510 - 3523
[18] Patent: WO2008/8398, 2008, A2, . Location in patent: Page/Page column 370
[19] Patent: WO2007/16525, 2007, A2, . Location in patent: Page/Page column 50
[20] Patent: JP2016/124812, 2016, A, . Location in patent: Paragraph 0307
[21] Journal of Organic Chemistry, 2007, vol. 72, # 2, p. 583 - 588
[22] Journal of Medicinal Chemistry, 2006, vol. 49, # 15, p. 4721 - 4736
[23] Patent: WO2008/36316, 2008, A2, . Location in patent: Page/Page column 32-33
[24] Patent: US2008/312209, 2008, A1, . Location in patent: Page/Page column 14
[25] Patent: WO2010/72722, 2010, A1, . Location in patent: Page/Page column 39
[26] Patent: WO2007/7018, 2007, A1, . Location in patent: Page/Page column 41
[27] Dalton Transactions, 2012, vol. 41, # 10, p. 2972 - 2978
[28] Journal of Medicinal Chemistry, 2012, vol. 55, # 22, p. 9589 - 9606
[29] Patent: US2013/281396, 2013, A1, . Location in patent: Paragraph 0308-0309
[30] Inorganic Chemistry, 2017, vol. 56, # 14, p. 7882 - 7889
[31] Patent: WO2018/52903, 2018, A1, . Location in patent: Page/Page column 70
[32] Patent: WO2018/102634, 2018, A1, . Location in patent: Page/Page column 83
[33] Patent: WO2005/9962, 2005, A1, . Location in patent: Page 25
  • 11
  • [ 874-24-8 ]
  • [ 62733-99-7 ]
YieldReaction ConditionsOperation in experiment
64% With sulfuric acid In methanol Step 1
Production of Methyl 3-hydroxypicolinate
3-Hydroxypicolinic acid (1.0 g) was suspended in methanol (10 ml) and concentrated sulfuric acid (1.0 ml) was added.
The mixture was refluxed under heating for 5 hr.
The reaction mixture was ice-cooled, neutralized with saturated aqueous sodium hydrogencarbonate, and extracted with chloroform.
The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate.
The solvent was evaporated under reduced pressure to give the title compound (711 mg, yield 64percent).
1H-NMR (300 MHz, CDCl3): 10.63 (1H, s), 8.28 (1H, dd, J=3.7, 1.8 Hz), 7.47-7.35 (2H, m), 4.06 (3H, s).
Reference: [1] Patent: US2003/50320, 2003, A1,
[2] Acta Chemica Scandinavica, 1998, vol. 52, # 11, p. 1327 - 1332
[3] Patent: US4083983, 1978, A,
[4] Patent: US2018/346438, 2018, A1,
  • 12
  • [ 36851-80-6 ]
  • [ 874-24-8 ]
  • [ 62733-99-7 ]
Reference: [1] Patent: US5294610, 1994, A,
  • 13
  • [ 186581-53-3 ]
  • [ 874-24-8 ]
  • [ 62733-99-7 ]
Reference: [1] Journal of Medicinal Chemistry, 1989, vol. 32, # 9, p. 2116 - 2128
[2] Helvetica Chimica Acta, 1980, vol. 63, # 6, p. 1400 - 1406
  • 14
  • [ 874-24-8 ]
  • [ 64-17-5 ]
  • [ 73406-50-5 ]
YieldReaction ConditionsOperation in experiment
73% With sulfuric acid In toluene at 95℃; for 72 h; Heating / reflux To 3-hydroxypyridine-2-carboxylic acid (25 g, 179.5 mmol) in a 1 L dried flask was added 400 mL ethanol and 100 mL toluene followed by the addition of 10 mL sulfuric acid. The mixture was heated at reflux (95° C.) for 3 days. After cooling to rt, the mixture was concentrated to 1/4 of its volume, and diluted with 600 mL ethyl acetate and 200 mL water. The aqueous layer was extracted with 200 mL ethyl acetate, and the combined organic layers were washed with sat NaHCO3 (3.x.200 mL), brine, and dried over Na2SO4. The solid was filtered off and the solvent was concentrated under reduced pressure to give 21.9 g of ethyl 3-hydroxypyridine-2-carboxylate (73percent), which was used in the next step without purification. This ester (21.9 g, 131 mmol) was dissolved in pyridine and cooled to -40° C., followed by addition of trifluoromethanesulfonic anhydride (48 g, 170 mmol). The reaction mixture was then warmed to 0° C. for 30 min, and then warmed to rt for another 30 min. Water (100 mL) was added to quench the reaction. The mixture was extracted with ethyl acetate (3.x.200 mL), and the combined organic layers were washed with sat sodium bicarbonate (200 mL), water (200 mL), brine (200 mL), and dried over sodium sulfate. The solid was filtered off, and the solvent was removed under reduced pressure to give 39 g (99percent) of desired product, which was used in the next step without further purification. 1H NMR (300 MHz, CD2Cl2) δ 8.73 (dd, 1H), 7.72 (dd, 1H), 7.62 (dd, 1H), 4.46 (q, 2H), 1.42 (t, 3H).
Reference: [1] Journal of Heterocyclic Chemistry, 1986, vol. 23, # 3, p. 665 - 668
[2] Patent: US2005/192294, 2005, A1, . Location in patent: Page/Page column 20-21
[3] Journal of Medicinal Chemistry, 2003, vol. 46, # 22, p. 4702 - 4713
[4] Patent: WO2005/42538, 2005, A1, . Location in patent: Page/Page column 15; 16
[5] MedChemComm, 2015, vol. 6, # 10, p. 1767 - 1772
  • 15
  • [ 874-24-8 ]
  • [ 73406-50-5 ]
Reference: [1] Journal of the Chemical Society, 1958, p. 4466,4468
[2] Patent: US6316464, 2001, B1,
  • 16
  • [ 874-24-8 ]
  • [ 59718-84-2 ]
Reference: [1] Tetrahedron Letters, 1996, vol. 37, # 4, p. 459 - 462
  • 17
  • [ 874-24-8 ]
  • [ 40966-87-8 ]
Reference: [1] Patent: US4022897, 1977, A,
  • 18
  • [ 874-24-8 ]
  • [ 39903-01-0 ]
Reference: [1] Patent: US4022897, 1977, A,
  • 19
  • [ 874-24-8 ]
  • [ 74-88-4 ]
  • [ 24059-83-4 ]
YieldReaction ConditionsOperation in experiment
62% With potassium carbonate In acetone for 12 h; Reflux To a stirred suspension of 3-hydroxypicolinic acid (350 mg, 2.52 mmol), K2CO3 (871 mg, 6.3 mmol) in acetone (25 mL) at rt was added CH3I (345 μL, 5.54 mmol) during 10 min. The mixture was refluxed for 12 h and the excess acetone was removed under reduced pressure. The residue was diluted with dichloromethane (DCM) and the organic phase was washed with water (2 times) and brine, dried over anhydrous Na2SO4 and concentrated under vacuum. The residue was chromatographed on silica gel [petroleum ether/EtOAc (PE/EA) = 1:2] to provide compound 5 (261 mg, 62percent) as colorless oil. 1H NMR (300 MHz, CDCl3) δ 8.29 (d, J = 4.4 Hz, 1H), 7.42 (dt, J = 16.5, 6.5 Hz, 2H), 3.98 (s, 3H), 3.93 (s, 3H).
62% With potassium carbonate In acetoneReflux Compound 3-Hydroxy-2-pyridinecarboxylic acid (350 mg, 2.52 mmol),Potassium carbonate (871 mg, 6.3 mmol) was suspended in 25 ml acetone.Stir at room temperature. Methyl iodide (345 μl, 5.54 mmol) was added dropwise to the above suspension.Heated to reflux overnight. Dry the solvent and dissolve the dichloromethane.Wash twice and wash once with saturated sodium chloride.Column chromatography (petroleum ether/ethyl acetate = 1/2) gave methyl 3-methoxy-2-picolinate (261 mg, 62percent) as a colorless oily liquid.
Reference: [1] European Journal of Medicinal Chemistry, 2017, vol. 125, p. 1051 - 1063
[2] Patent: CN103539731, 2018, B, . Location in patent: Paragraph 0092; 0095; 0096
[3] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 3, p. 635 - 638
  • 20
  • [ 874-24-8 ]
  • [ 24059-83-4 ]
Reference: [1] Patent: US2013/281396, 2013, A1,
[2] ChemMedChem, 2016, vol. 11, # 23, p. 2607 - 2620
[3] Patent: WO2018/52903, 2018, A1,
  • 21
  • [ 874-24-8 ]
  • [ 16478-52-7 ]
Reference: [1] European Journal of Medicinal Chemistry, 2017, vol. 125, p. 1051 - 1063
  • 22
  • [ 874-24-8 ]
  • [ 272-62-8 ]
Reference: [1] Journal of Heterocyclic Chemistry, 1986, vol. 23, # 3, p. 665 - 668
  • 23
  • [ 874-24-8 ]
  • [ 676-58-4 ]
  • [ 13210-29-2 ]
YieldReaction ConditionsOperation in experiment
77%
Stage #1: With triethylamine In tetrahydrofuran at 60 - 65℃; for 5 h;
Stage #2: With Methyl formate In tetrahydrofuran at 5 - 20℃;
Stage #3: With hydrogenchloride; water In tetrahydrofuran at 10℃;
Example 2; 3-methyl-N4[(1S)-3-methyl-1-([(4S,7R)-7-methyl-3-oxo-1-(2-pyridinylsulfonyl) hexahydro-1H-azepin-4-yl]amino}carbonyl)butyl]furo[3,2-b]pyridine-2-carboxamide; Preparation of 3-methylfuro[3,2-b]pyridine-2-carboxylic acid (6-1); Under nitrogen, charge the flask with 3 M methyl magnesium chloride in THF (600 mL, 1.80 mol, 5.0 equiv) and THF (500 mL). Heat the solution to 60-65° C. and add a solution of 3-hydroxypicolinic acid (1) (50 g, 0.36 mole), triethylamine (50 mL, 0.36 mole) in THF (250 mL) to the reaction mixture over approximately 3 h. Continue heating at reflux for 2 h. Cool the reaction to 5-10° C. and add methyl formate (44 mL) keeping the reaction temperature less than 20° C. At 10° C., add 10percent aqueous HCl to a pH 34. Transfer to separatory funnel and allow the layers to separate. Remove the top organic phase and extract the aqueous phase with THF (250 mL). Combine the organic phases combined and concentrate to 13-15 volumes and add water (170 mL). Continue with the vacuum distillation until all the THF has been removed. Cool the solution to 10° C., stir 0.5 h, filter and dry 1-(3-hydroxypyridin2-yl)ethanone (2) as the tan solid (38.1 g, 77percent yield).
Reference: [1] Patent: US2008/262224, 2008, A1, . Location in patent: Page/Page column 14-15
  • 24
  • [ 874-24-8 ]
  • [ 75-16-1 ]
  • [ 13210-29-2 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 13, p. 3398 - 3404
  • 25
  • [ 874-24-8 ]
  • [ 13210-29-2 ]
Reference: [1] Journal of Heterocyclic Chemistry, 1986, vol. 23, # 3, p. 665 - 668
  • 26
  • [ 874-24-8 ]
  • [ 51984-46-4 ]
Reference: [1] ChemMedChem, 2016, vol. 11, # 23, p. 2607 - 2620
[2] Patent: WO2018/52903, 2018, A1,
  • 27
  • [ 874-24-8 ]
  • [ 321596-55-8 ]
Reference: [1] Patent: US6355660, 2002, B1,
[2] Patent: WO2018/5662, 2018, A1,
[3] Patent: WO2018/102634, 2018, A1,
  • 28
  • [ 874-24-8 ]
  • [ 321596-58-1 ]
YieldReaction ConditionsOperation in experiment
12%
Stage #1: With N-Bromosuccinimide In N,N-dimethyl-formamide for 1 h;
Stage #2: With water; sodium hydroxide In N,N-dimethyl-formamide
INTERMEDIATE A5 -Bromo-S-hydroxypyridine-l-carboxylic acid To a stirred suspension of 3-hydroxypyridine-2-carboxylic acid (2.00 g, 0.0144 mol) in DMF (30 mL) was added a solution of N-bromosuccinimide (2.56 g, 0.0144 mol) in DMF (30 mL). After 1 h, water (50 mL) and 1 M aqueous NaOH (25 mL) were added and the resulting mixture was extracted with chloroform (3 x 150 mL). The organic layers were combined and concentrated and the residue was purified by preparative HPLC (System D). Yield 366 mg (12percent). Analytical HPLC: purity 100percent (System A and B); LRESIMS (ESI+) m/z = 218/220 (M+H)+.
Reference: [1] Patent: WO2009/150144, 2009, A1, . Location in patent: Page/Page column 63
  • 29
  • [ 874-24-8 ]
  • [ 1256810-26-0 ]
Reference: [1] Patent: WO2014/121418, 2014, A1,
  • 30
  • [ 874-24-8 ]
  • [ 945954-94-9 ]
Reference: [1] Patent: WO2014/121418, 2014, A1,
[2] Patent: EP3255042, 2017, A2,
Recommend Products
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 874-24-8 ]

Alcohols

Chemical Structure| 62733-99-7

[ 62733-99-7 ]

Methyl 3-hydroxypicolinate

Similarity: 0.92

Chemical Structure| 14162-88-0

[ 14162-88-0 ]

3-Hydroxy-6-methylpicolinic acid

Similarity: 0.90

Chemical Structure| 321596-58-1

[ 321596-58-1 ]

6-Bromo-3-hydroxypicolinic acid

Similarity: 0.85

Chemical Structure| 22468-26-4

[ 22468-26-4 ]

4-Hydroxypicolinic acid

Similarity: 0.83

Chemical Structure| 61548-52-5

[ 61548-52-5 ]

Methyl 3-hydroxy-6-methylpicolinate

Similarity: 0.83

Carboxylic Acids

Chemical Structure| 16478-52-7

[ 16478-52-7 ]

3-Methoxypicolinic acid

Similarity: 0.92

Chemical Structure| 14162-88-0

[ 14162-88-0 ]

3-Hydroxy-6-methylpicolinic acid

Similarity: 0.90

Chemical Structure| 103878-09-7

[ 103878-09-7 ]

3-Ethoxypicolinic acid

Similarity: 0.89

Chemical Structure| 321596-58-1

[ 321596-58-1 ]

6-Bromo-3-hydroxypicolinic acid

Similarity: 0.85

Chemical Structure| 98-98-6

[ 98-98-6 ]

2-Pyridinecarboxylic acid

Similarity: 0.84

Related Parent Nucleus of
[ 874-24-8 ]

Pyridines

Chemical Structure| 16478-52-7

[ 16478-52-7 ]

3-Methoxypicolinic acid

Similarity: 0.92

Chemical Structure| 62733-99-7

[ 62733-99-7 ]

Methyl 3-hydroxypicolinate

Similarity: 0.92

Chemical Structure| 14162-88-0

[ 14162-88-0 ]

3-Hydroxy-6-methylpicolinic acid

Similarity: 0.90

Chemical Structure| 24059-83-4

[ 24059-83-4 ]

Methyl 3-methoxypyridine-2-carboxylate

Similarity: 0.89

Chemical Structure| 103878-09-7

[ 103878-09-7 ]

3-Ethoxypicolinic acid

Similarity: 0.89