ChemicalBook CAS DataBase List Ritonavir

Ritonavir synthesis

8synthesis methods

Product Name:Ritonavir
CAS Number:155213-67-5
Molecular formula:C37H48N6O5S2
Molecular Weight:720.94

(S)-2-(3-((2-Isopropylthiazol-4-yl)methyl)-3-methylureido)-3-methylbutanoic acid

154212-61-0

(2S,3S,5S)-5-Amino-2-(N-((5-thiazolyl)-methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane

144164-11-4

155213-67-5

37.6 g (120.0 mmol) of (S)-2-(3-((2-isopropylthiazol-4-yl)methyl)-3-methylureido)-3-methylbutanoic acid, 15.1 g (120.0 mmol) of DIC (N,N'-diisopropylcarbodiimide), 35.0 g of N,N-diisopropylethylamine and 200 ml of cyclopentanone were mixed and stirred under 27° C for 0.5 hours. Subsequently, the mixture was slowly added to a 150 ml solution of cyclopentanone containing 42.6 g (100 mmol) of (2S,3S,5S)-5-amino-2-(N-((5-thiazolyl)-methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane, and the reaction was stirred for 7 hours, during which time the progress of the reaction was monitored by TLC. After completion of the reaction, the reaction solution was washed with 350 ml x 2 of 10% NaCl solution and pure water and the aqueous layer was discarded. The organic phase was dried with anhydrous sodium sulfate for 6 hours and filtered. The filtrate was heated to 45-50°C, decolorized by adding 0.8 g of activated carbon, stirred for 15 min and then cooled to 20-30°C and filtered. The filtrate was concentrated under vacuum to an oil, which was subsequently dissolved in 230 ml of butyl acetate, heated to 60°C to dissolve completely, cooled naturally to 20-30°C and stirred for 12 hours. After filtration, the filter cake was washed with 40 ml of cold butyl acetate and finally dried under vacuum at 50°C for 6 hours to give 66.3 g of white crystalline target product in 91.5% yield.

154212-61-0 Synthesis

154212-61-0
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$5.00/1g

144164-11-4
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$96.00/1g

155213-67-5
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$5.00/10mg

Yield:155213-67-5 91.5%

Reaction Conditions:

Stage #1: N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)-carbonyl)-L-valinewith N-ethyl-N,N-diisopropylamine;diisopropyl-carbodiimide at 27; for 0.5 h;
Stage #2: (2S,3S,5S)-5-Amino-2-(N-((5-thiazolyl)-methoxycarbonyl)amino)-3-hydroxy-1,6-diphenylhexane for 7 h;Temperature;

Steps:

2 Preparation of Embodiment 2: ritonavir

In the 27 °C lower, the compound N - [N - methyl - N - [(2 - isopropyl -4 - thiazolyl) methyl] aminocarbonyl] - L - valine 37.6g (120.0mmol), 15.1g (120.0mmol) DIC (N, N' - diisopropyl carbodiimide), 35.0gN, N - diisopropyl ethylamine and 200 ml of cyclopentanone mixing 0.5h. The mixture into the to 42.6g (100mmol) (2S, 3S, 5S) -5 - amino -2 - (N - ((5 - thiazolyl) - methoxycarbonyl) amino) - 1, 6 - diphenyl -3 - hydroxy hexane 150 ml of cyclopentanone in stirring 7h, TLC detection, said technological, turn the reaction liquid 10% sodium chloride and purified water washing 350 ml × 2, abandoned to the aqueous layer, the organic phase adding anhydrous sodium sulfate drying 6h after-filtration, then the filtrate is heated to 45 - 50 °C, at the same time adding 0.8g activated carbon to decolorize the, stirring 15min, cooling to 20 - 30 °C filter, vacuum concentrated organic phase to be oily lito that wei Cupin, up into the oil objects in 230 ml butyl acetate, then heating to 60 °C, to dissolve it completely, natural cooling to 20 - 30 °C, and stirring 12h, filtering, cold-butyl acetate 40 ml washing the filter cake, vacuum 50 °C drying 6h, obtaining white crystalline grain product ritonavir 66.3g, yield 91.5%,

References:

CN106749085,2017,A Location in patent:Paragraph 0020; 0021; 0022; 0023