ChemicalBook CAS DataBase List Silodosin

Silodosin synthesis

6synthesis methods

Product Name:Silodosin
CAS Number:160970-54-7
Molecular formula:C25H32F3N3O4
Molecular Weight:495.53

Silodosin is an α1-adrenoceptor antagonist approved for the symptomatic treatment of benign prostatic hyperplasia. It acts as an α1-adrenoceptor antagonist with high uroselectivity (selectivity for the prostate). Since silodosin has high affinity for the α1A adrenergic receptor, it causes practically no orthostatic hypotension (in contrast to other α1 blockers). On the other side, the high selectivity seems to be the cause of silodosin's typical side effect of retrograde ejaculation.

Synthetic Routes

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Yamaguchi, Toshiaki; Tsuchiya, Ikuo; Kikuchi, Ken; Yanagi, Takashi. Process for preparation of silodosin. Assignee Kissei Pharmaceutical Co., Ltd., Japan. WO 2006046499. (2006).

1H-Indole-7-carbonitrile, 2,3-dihydro-1-(3-hydroxypropyl)-5-[(2R)-2-[[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl]aMino]propyl]-

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Yield:160970-54-7 96.24%

Reaction Conditions:

Stage #1: 1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7-carbonitrilewith potassium carbonate in water; pH=9;
Stage #2: with cesium hydroxide;dihydrogen peroxide in dimethyl sulfoxide at 20; for 2 h;

Steps:

18 Example 18 1- (3-hydroxypropyl) -5-[(2R) -2- [2- [2- (2,2,2-trifluoroethoxy) phenoxy] ethyl] amino] propyl] indoline-7-carboxamideProduction of (compound of formula 1, silodosin)

Manufactured in Example 171- (3-hydroxypropyl) -5-[(2R) -2- [2- [2- (2,2,2-trifluoroethoxy) phenoxy] ethyl] aminopropyl] indoline-7-carbonitrile(Compound of Chemical Formula 2a) Oxalate (25 g, 44 mmol)Is suspended in purified water (100 mL),The pH was adjusted to 9 or more by adding 1 N K2CO3 solution.The reaction mixture was extracted with dichloromethane (100 mL × 2).The combined organic layers were dried over MgSO 4 and filtered.The filtrate is concentrated under reduced pressure,Vacuum dried.The resulting product is dissolved in 60 ml of dimethyl sulfoxide and cooled to 20 ° C. or less.30% hydrogen peroxide (15.2 mL, 2 equivalents) was added slowly.Add cesium hydroxide (12.7 g, 1 equivalent) at the same temperature,The temperature was gradually raised to room temperature and vigorously stirred for 2 hours.Add 5% aqueous sodium sulfite solution (120 mL),Extracted with dichloromethane (100 mL × 2).Combine the organic layers and wash thoroughly with water and brine,After drying over anhydrous sodium sulfate, it was filtered. The filtrate is concentrated under reduced pressure, dried under vacuum, and the residue is recrystallized with ethyl acetate (120 mL).Vacuum dry,21 g of the title compound were obtained.(Yield: 96.24%,HPLC purity: 99.95%)

References:

JP2019/31488,2019,A Location in patent:Paragraph 0054