Reference of 112101-81-2,Some common heterocyclic compound, 112101-81-2, name is R-5-(2-Aminopropyl)-2-methoxybenzenesulfonamide, molecular formula is C10H16N2O3S, 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 1: Preparation of 5-[(2R)-2-[[2-(2-ethoxyphenoxy)ethyl]amino]propyl]-2- methoxybenzene-sulfonamide (Tamsulosin base)(R)-5-(2-arriinopropyl)-2-methoxybenzenesurfonarnide (60 g; 245.59 mmol) and l-(2- bromoethoxy)-2-ethoxybenzene (57.25 g; 233 mmol) were dissolved in 240 mL of N5N- dimethylformamide and 50.5 mL of diisopropylethylamine. The reaction mixture was heated to 100 C and stirred for 90 minutes. The mixture was then cooled to 20 C and 720 mL of ethyl acetate and 300 mL of water added to the vessel. The mixture was then stirred for 20 minutes at atmospheric condition, and then was allowed to settle. The aqueous layer was separated and re-extracted twice with 300 mL of ethyl acetate. The organic layers were combined and washed with 600 mL of water.The organic phase (1120 mL of ethyl acetate) was then concentrated by distillation at atmospheric pressure during which a white solid was precipitated. The mixture was then cooled to 2 C and stirred for 1 hour. The resulting crystals were isolated by filtration and washed with ethyl acetate to yield 133.59 g of wet tamsulosin base (Loss on Drying: 55.08% (corresponding to 60.01 g of dry material); HPLC Purity: 95.025%).EXAMPLE 3: Preparation of 5-[(2R)-2-[[2-(2-ethoxyphenoxy)ethyl]amino]propyl]-2- methoxybenzene-sulfonamide (Tamsulosin base)(R)-5-(2-aminopropyl)-2-methoxybenzenesulfonamide (100 g; 409.31 mmol) and 1- (2-bromoethoxy)-2-ethoxybenzene (95.4 g; 388 mmol) were dissolved in 400 mL of N,N- dimethylformamide and 84 mL of diisopropylethylamine. The reaction mixture was heated to 100 C and stirred for 90 minutes. The mixture was then cooled to 20 C, and 1200 mL of ethyl acetate and 500 mL of water were added. The mixture was then stirred for 20 minutes at atmospheric conditions and was allowed to settle. The aqueous layer was then separated and re-extracted twice with 500 mL of ethyl acetate. Next, the organic layers were combined and washed with 1000 mL of water.The organic phase (~1570 mL of ethyl acetate) was then concentrated by distillation at atmospheric pressure during which a white solid was precipitated. The mixture was then cooled to 2 C, and stirred for 1 hour. The resulting crystals were isolated by filtration and washed with ethyl acetate to yield 125.93 g of wet tamsulosin base (Loss on Drying: 24.09% (corresponding to 95.59 g of dry material); HPLC Purity: 97.62%).
The synthetic route of 112101-81-2 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; MEDICHEM, S.A.; WO2007/119110; (2007); A2;,
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