Amlodipine

Amlodipine is a long-acting calcium channel blocker.Target: Calcium ChannelAmlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the movement of calcium ions into vascular smooth muscle cells and cardiac muscle cells. Experimental data suggest amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of ext

(R, S)-Amlodipine besylate (5.342 g) was suspended in water (100 mL). The resultant mixture was brought to reflux while stirring. NaOH (0.4 g) was added to the resultant yellow solution, and the solution was allowed to reflux for a further 30 minutes. The mixture was subsequently allowed to cool overnight, and the resultant precipitate was filtered and dried under vacuum to provice 3.41 g (88.6 percent yield) of amlodipine (free base). Melting point 133-138Stage -3: Preparation of Amlodipine from Phthalimido amlodipine:Pure Phthalimido amlodipine (50 g) prepared as above is suspended in ethanolic methylamine (600 ml) and maintained for 17 hrs at 28°C - 32°C. The reaction mass is slowly poured into hot water (1200 ml) held at 50°C - 55°C over 45 min and mixed for about 1 hr at 50°C - 55°C. Reaction mass is slowly cooled and maintained for about 1 hr at 20°C - 25°C. The precipitated solid is filtered, washed the wet cake with water. Dried the product at 55°C - 60°C till constant weight.Dry weight of the Amlodipine base is 33.0 g (Yield: 87.2percent).Preparation of 3-Ethyl, 5-methyl (4RS) 2-[(2-AMINOETHOXY) METHYLL-4-(2-CHLOROPHENYL)-6-METHYL-1, 4-dihydro pyridine-3, 5-dicarboxylate (IV) A 100 L reactor was charged with 7.0 kg of phthaloyl amlodipine and 33.5 kg of toluene. Hydrazine hydrate 5. 1 kg was mixed with 10.0 kg of methanol in a 25 L reactor and was added into the stirring suspension of phthaloyl amlodipine at 22-24 °C. The solution was stirred for 7h at this temperature. The solid material phthalhydrazide was filtered off. The organic phase was washed with 2 X 20 L of MGSOI7 H20. After separating the phases, organic phase dried over 1.28 kg of MGS04 and filtered. The solution was concentrated to 1/3 of its original volume and 24 kg of n-hexanes was added. The mixture was cooled down to 0- 5 °C and kept at this temperature for 2h with stirring and then 12h without stirring. The product was filtered off and dried in oven under vacuum at 55 °C for 12h to give 4.6 kg of amlodipine base in 86.5percent yield as AWHITE POWDER. LH-NMR (CDC13) 6 7.85 (s, 1H), 7.20 (m, 4H), 5. 38 (s, 1H), 4.78 (d, 1H), 4.70 (d, 1H), 3.95 (m, 2H), 3.60 (s, 3H), 3.57 (d, 2H), 2.95 (M, 2H), 2.34 (s, 3H), 1.17 (t, 3H). 13C-NMR (CDCL3) No. 168.3, 167.4, 157.1, 146.2, 146.1, 144.6, 132.5, 131.7, 129.4, 127.5, 127.0, 104.0, 101.5, 73.5, 68.2, 60.0, 51.0, 41.3, 37.3, 19. 4, 14.5.General procedure: To a 50-ml glass round-bottom flask was added sequentially the primary amine 2 (1.0 mmol; aliphatic, aromatic or heteroaromatic; as free naked amine or as HCl, MsOH, TsOH or tartrate salt), FSO2N3 solution (containing 1.0 mmol FSO2N3, approximately 200 mM in DMF/MTBE 1:1, v/v, approximately 5 ml, volume adjusted according to the concentration; prepared according to the above procedure and diluted with equal volume of DMF) and aqueous KHCO3 solution (3.0 M, 1.33 ml, containing 4.0 mmol KHCO3). The reaction mixture was stirred for 5 min at room temperature, while monitoring by LC-MS. After completion, EtOAc (40 ml) was added and the mixture was washed sequentially with brine (60 ml × 6), water (60 ml × 2) and brine (60 ml), dried over Na2SO4, concentrated by rotary evaporation and dried under vacuum to afford the azide product 3. For products containing acidic functional groups, this extraction process was modified with acidified aqueous phase (acidified with aqueous HCl). Detailed procedures and the various modifications, as well as the characterization data for each compound, can be found in Supplementary Information 1.Accurately referred to as compound S23 take 500mg of 2.34mmol ie, dissolved in acetonitrile and added 1.0g About 2.53mmol amlodipine, i.e., 3-ethyl-5-methyl-2 - ((2-amino) methyl) -4- (2- Chloro) -6-methyl-1, 4-dihydropyridine-3, 5-dicarboxylic acid ester, 1.04g of potassium carbonate powder and about 7.59mmol 35a catalytic amount of about 0.23mmol mg NaI, the reaction system was transferred to 80 C in an oil bath at reflux, TLC Tracking and monitoring, 16h After completion of the reaction, the reaction was stopped, the organic solvent is evaporated, the reaction mixture was subjected to silica Gel column chromatography chromatography using the elution system containing 1% triethylamine, eluent petroleum ether and wherein Ethyl acetate in a volume ratio of 2:1-1:1 elution gradient, to give the compound of the present invention provides 7, 750mg, 54.1% yield.

A deuterated dihydropyridine calcium channel blocker.;Application of Labeled APIs: Labeled Amlodipine, intended for use as an internal standard for the quantification of Amlodipine by GC- or LC-mass spectrometry.

Molecular Weight:408.9
XLogP3:3
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:7
Rotatable Bond Count:10
Exact Mass:408.1451996
Monoisotopic Mass:408.1451996
Topological Polar Surface Area:99.9
Heavy Atom Count:28
Complexity:647
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes