* 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.
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 4, p. 609 - 612
[2] Patent: WO2004/37808, 2004, A1, . Location in patent: Page 9-10
[3] Chemische Berichte, 1954, vol. 87, p. 1868
2
[ 39977-44-1 ]
[ 69950-65-8 ]
Yield
Reaction Conditions
Operation in experiment
87%
With manganese(IV) oxide In dichloromethane at 25℃; for 96 h;
A solution of the product from Example 17A (8 g, 48 mmol) in dichloromethane (200 mL) was treated with electrolytic manganese dioxide (41.67 g, 0.48 mol). The mixture was stirred for 4 days at 25° C. and filtered through celite. The filtrate was concentrated under reduced pressure and the residue was purified by chromatography on silica gel eluting with 5percent methanol in dichloromethane to give the title compound as a white solid (6.9 g, 87percent yield).
79%
With manganese dioxide In 1,2-dichloro-ethane
EXAMPLE 18 Preparation of 6-formylpyridine-2-carboxylic Acid Methyl Ester (IVo) A solution of 3 g of 6-hydroxymethylpyridine-2-carboxylic acid methyl ester (16.5 mmol) in 70 ml of 1,2-dichloroethane containing 15 g of manganese dioxide (165 mmol) is heated under reflux for 4 hours with removal of the water formed continuously. The solid is removed by filtration on celite and then the dichloromethane is evaporated off. The title product is isolated by chromatography on a silica column (eluent: dichloromethane/ethyl acetate; 70:30). 2.33 g of a yellow oil are recovered. Yield: 79percent 1 H NMR (CDCl3) δ: 1.36 (t, 3H); 4.41 (m, 2H); 8.13 (dd, 1H); 8.24 (t, 1H); 8.32 (dd, 1H); 10.02 (s, 1H). IR (film) σ: 1700 cm-1 (C=O).
21%
With manganese(IV) oxide In dichloromethane at 20℃; for 120 h;
This compound was synthesized after a modified published procedure [28]. Methyl-6-(hydroxymethyl)picolinate (1 g, 6 mmol) was dissolved in dichloromethane (25 mL), and manganese dioxide (5.2 g, 80 mmol) was added. The suspension was stirred at room temperature for 5 days and subsequently filtered through Celite. The filtrate was concentrated in vacuo, and the crude product was purified using flash column chromatography (dichloromethane/methanol 85:15, I2 stain, Rf = 0.73) to yield 206 mg (21percent) of a white solid (250 mg of starting material were re-isolated). 1H NMR (CDCl3, 500.13 MHz); δ 4.05 (s, 3H, OCH3); 8.03 (td, 1H, pyH, J = 7.7, 0.8 Hz); 8.12 (dd, 1H, pyH, J = 7.8, 1.2 Hz); 8.33 (dd, 1H, pyH, J = 7.7, 1.2 Hz); 10.17 (d, 1H, CHO, J = 0.8 Hz). 13C NMR (CDCl3, 100.62 MHz); δ 53.3 (OCH3); 124.4 (pyCH); 129.0 (pyCH); 138.4 (pyCH); 148.6 (pyC); 152.8 (pyC); 164.9 (CO2CH3); 192.6 (CHO). ESI mass spectrometry (methanol) m/z 188.30 [C8H7NO3+Na]+. FT-IR spectroscopy (v, cm-1) 2860.8 (w, C-H str); 1719.4, 1708.2 (s, C=O str); 1140.9 (m, C-O str); 762.5 (m, py-H def). m.p. 82.4-84.2 °C.
Reference：
[1] Patent: US2005/131017, 2005, A1, . Location in patent: Page/Page column 106
[2] Patent: US6020345, 2000, A,
[3] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 4, p. 609 - 612
[4] Patent: WO2004/37808, 2004, A1, . Location in patent: Page 9-10
[5] Chemistry of Heterocyclic Compounds, 2009, vol. 45, # 2, p. 161 - 168
[6] Journal of Medicinal Chemistry, 2018, vol. 61, # 7, p. 2753 - 2775
[7] Dalton Transactions, 2011, vol. 40, # 23, p. 6253 - 6259
[8] Polyhedron, 2013, vol. 52, p. 1336 - 1343
[9] Chemistry - A European Journal, 2004, vol. 10, # 14, p. 3579 - 3590
[10] Patent: US2004/204455, 2004, A1, . Location in patent: Page/Page column 19
3
[ 5453-67-8 ]
[ 69950-65-8 ]
Yield
Reaction Conditions
Operation in experiment
29%
Stage #1: With methanol; sodium tetrahydroborate In tetrahydrofuran at 70 - 75℃; for 1 h; Stage #2: With manganese(IV) oxide In chloroform; toluene at 20℃; for 18 h;
Step 1: Preparation of methyl 6-formylpyridine-2-carboxylate (I-33a) A suspension of dimethylpyridine-2,6-dicarboxylate (1.0 g, 5.12 mmol) in methanol (8 mL) and THF (3 mL) was heated at 75° C. until the solid was dissolved. NaBH4 (184 mg, 4.87 mmol) was then added portion-wise. The mixture was stirred at 70° C. for 1 h. The mixture was cooled to room temperature and 10percent citric acid (1.6 mL) was added. The solution was filtered and the filtrate was evaporated to dryness, taken up in dichloromethane, dried over MgSO4 and the solvent was removed in vacuo. The residue was purified by silica gel chromatography, eluting with 0-100percent EtOAc in isohexane, to provide a colourless oil which was then dissolved in toluene (20 mL) and chloroform (20 mL). MnO2 (194 mg, 22.2 mmol) was added and the mixture was stirred at room temperature for 18 h. The mixture was filtered through a pad of fluorosil, eluting with chloroform (30 mL) and the solvent was removed in vacuo to provide the title compound (249 mg, 29percent) as white solid. 1H NMR (400 MHz, CDCl3): δ 10.20 (s, 1H), 8.37 (dd, J=1.2, 7.6 Hz, 1H), 8.17 (dd, J=1.2, 7.6 Hz, 1H), 8.08-8.04 (m, 1H), 4.07 (s, 3H).
29%
Stage #1: With methanol; sodium tetrahydroborate In tetrahydrofuran; methanol at 70 - 75℃; Stage #2: With manganese(IV) oxide In chloroform; toluene at 20℃; for 18 h;
A suspension of dimethyl pyridine-2,6-dicarboxylate (1.0 g, 5.12 mmol) in methanol (8 mL) and THF (3 mL) was heated at 75°C until the solid was dissolved.NaBH4 (184 mg, 4.87 mmol) was then added portion-wise. The mixture was stirred at70°C for 1 h. The mixture was cooled to room temperature and 10percent citric acid (1.6 mL)was added. The solution was filtered and the filtrate was evaporated to dryness, taken upin dichloromethane, dried over Mg504 and the solvent was removed in vacuo. Theresidue was purified by silica gel chromatography, eluting with 0-100percent EtOAc in isohexane, to provide a colourless oil which was then dissolved in toluene (20 mL) and chloroform (20 mL). Mn02 (194 mg, 22.2 mmol) was added and the mixture was stirred at room temperature for 18 h. The mixture was filtered through a pad of fluorosil, eluting with chloroform (30 mL) and the solvent was removed in vacuo to provide the titlecompound (249 mg, 29percent) as white solid.‘H NMR (400 MHz, CDC13): ö 10.20 (s, 1 H), 8.37 (dd, J = 1.2, 7.6 Hz, 1 H), 8.17(dd, J = 1.2, 7.6 Hz, 1 H), 8.08-8.04 (m, 1 H), 4.07 (s, 3 H).
Reference：
[1] Journal of Chemical Research, Miniprint, 1998, # 10, p. 2736 - 2753
[2] Patent: US2015/158858, 2015, A1, . Location in patent: Paragraph 0489; 0490; 0491
[3] Patent: WO2015/82616, 2015, A1, . Location in patent: Page/Page column 107; 108
[4] Chemistry - A European Journal, 2004, vol. 10, # 14, p. 3579 - 3590
[5] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 4, p. 609 - 612
4
[ 129747-52-0 ]
[ 69950-65-8 ]
Yield
Reaction Conditions
Operation in experiment
71%
With Dess-Martin periodane In dichloromethane for 16 h;
To a solution of the alcohol (655 mg, 3.92 mmol.) in DCM (7 mL) was added Dess-Martin periodinane (3.3 g, 7.84 mmol.). Stirred for 16h, then diethyl ether was added. The reaction was concentrated, and then partitioned between diethyl ether and a solution of sodium thiosulfate (6.8 g, 43.12 mmol.) in saturated NaHCO3 (50 mL). The aqueous layer was extracted using diethyl ether (2.x.). The combined organic extracts were dried with MgSO4 and concentrated. The crude product was purified by column chromatography to yield 6 (460 mg, 2.78 mmol, 71percent). 1H-NMR (DMSO-d6): δ=10.03 (s, 1H), 8.33 (d, J=8Hz, 1H), 8.25 (dd, J=8 Hz+8 Hz, 1H), 8.15 (d, J=8 Hz, 1H), 3.95 (s, 3H). Calculated mass=165.1, [M]+=165.
2-[(6-[tert-Butoxycarbonyl-(2-tert-butoxycarbonylamino-ethyl)-amino]-methyl}-1-oxy-pyridine-2-carbonyl)-amino]-3-(1H-imidazol-4-yl)-propionic acid methyl ester[ No CAS ]
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