The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.
Application of 112101-81-2, A common heterocyclic compound, 112101-81-2, name is R-5-(2-Aminopropyl)-2-methoxybenzenesulfonamide, molecular formula is C10H16N2O3S, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
EXAMPLE 4:Preparation of By-Product (5-((R)-2-{Bis-[2-(2-ethoxy phenoxy)ethyI]amino}-propyl)-2-methoxy benzene sulfonamide)This example demonstrates how by-product 5-((R)-2-{Bis-[2-(2-ethoxyphenoxy) ethyl]amino}-propyl)-2-methoxybenzenesulfonamide is prepared by reacting the (R)- enantiomer of reactant-V according to prior processes. A round-bottomed flask is charged with 4.0 g (16.37 mmol) of (R)-reactant-V, 3.47 g (32.74 mmol) OfNa2CO4, 8.01 g (32.65 mmol) of the bromide form of reactant-VI, and 24 mL of N,N-dimethylformamide. Notably, alkyl phosphite solvent was not used in this example. The mixture is heated up to 80 C, and is stirred overnight at 80 C, and then the mixture is cooled down to about 20-25 C. EPO At this point, 40 mL of water and 40 mL of AcOEt are charged into the flask and the resulting mixture is then stirred for 30 minutes and left to decant. The organic phase is separated and then charged again into the flask, is reintroduced in the flask and washed with slightly acidic water (pH 5). The mixture is let to decant and the organic phase is dried with Na2SO4 and the solvent evaporated to obtain 8.96 g of crude 5-((R)-2-{Bis-[2-(2- ethoxyphenoxy)ethyl]amino}-propyl)-2-methoxybenzene sulfonamide. The crude product was purified by silica gel column chromatography (AcOEt as eluent) to obtain 6.29 g of 5- ((R)-2- {Bis-2-(2-ethoxyphenoxy)ethyl]amino } -propyl)-2-methoxybenzenesulfonamide, which still was unpurified and contained unused reactant-VI. A second silica gel column chromatography (CHCI3 as eluent) was performed to obtain 6.00 g of purified 5-((R)-2-{Bis- [2-(2-ethoxyphenoxy)ethyl]amino}-propyl)-2-methoxybenzenesulfonamide (yield 64%).Prior to purification by gel column chromotography, the crude product has approximately 9% (area) tamsulosin free base and approximately 73.3% (area) of the byproduct. Following purification by gel column chromotography, tamsulosin free base is not detected according to HPLC method 1 analysis.The 1H-NMR pMSO-d6, 300 MHz), delta (ppm) of the byproduct is characterized as follows: 0.94 (d, 3H, NCHCH3); 1.24 (t, 6H, OCH2CH3); 2.49 (m (overlapped with DMSO-d5), IH, Ar- CHA); 2.84 (dd, IH, Ar-CHB); 2.89-3.05 (complex signal , 5H, N(CH2-)2 and NH-CHCH3); 3.83 (s, 3H, OCH3); 3.78-4.01 (complex signal, 8H52 OCH2CH3 and 2 NHCH2CH2O); 6.79-6.94 (complex signal, 8H, Ar-H of Ar-OEt); 6.97 (broad s, 2H SO2NH2); 7.00, (d, IH, 3-H (Ar- SO2NH2)); 7.41 (dd, IH, 4-H (Ar-SO2NH2); 7.57 (d, IH, 6-H (Ar-SO2NH2));The 13C NMR (DMSO-d6, 300 MHz), delta (ppm) of the byproduct is characterized as follows: 14.9 (2CH3, 2 OCH2CH3); 15.3 (CH3, CHCH3); 38.3 (CH2 , ArCH2); 50.1 (2 CH2, 2 OCH2CH2N); 56.1 (CH3, OCH3); 59.2 (CH, CHCH3); 63.9 (2 CH2, 2OCH2CH3); 68.6 (2 CH2, 2 OCH2CH2N); 112.4 (CH, C3 (Ar-SO2NH2)); 113.6 , 113.7 and 120.9 (2 x 4CH (Ar-OEt)); 128.1 (CH, C6 (Ar-SO2NH2); 130.9 and 132.3 (2 x C, Ci and C5 (Ar-SO2NH2)); 134.3 (CH, C4 (Ar-SO2NH2); 148.4 and 148.5 2 X 2C (Ar-OEt); 154.2 (C, C2 (Ar-SO2NH2).
The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.
Reference:
Patent; MEDICHEM, S.A.; WO2007/4077; (2007); A2;,
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics