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1190307-88-0

1190307-88-0

Identification

  • Product Name:Sofosbuvir

  • CAS Number: 1190307-88-0

  • EINECS:695-717-4

  • Molecular Weight:529.459

  • Molecular Formula: C22H29FN3O9P

  • HS Code:29339900

  • Mol File:1190307-88-0.mol

Synonyms:N-[[P(S),2'R]-2'-Deoxy-2'-fluoro-2'-methyl-P-phenyl-5'-uridylyl]-L-alanine 1-methylethyl ester;

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Safety information and MSDS view more

  • Signal Word:Warning

  • Hazard Statement:H373 May cause damage to organs through prolonged or repeated exposure

  • First-aid measures: General adviceConsult a physician. Show this safety data sheet to the doctor in attendance.If inhaled If breathed in, move person into fresh air. If not breathing, give artificial respiration. Consult a physician. In case of skin contact Wash off with soap and plenty of water. Consult a physician. In case of eye contact Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician. If swallowed Never give anything by mouth to an unconscious person. Rinse mouth with water. Consult a physician.

  • Fire-fighting measures: Suitable extinguishing media Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. Wear self-contained breathing apparatus for firefighting if necessary.

  • Accidental release measures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. For personal protection see section 8. Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Pick up and arrange disposal. Sweep up and shovel. Keep in suitable, closed containers for disposal.

  • Handling and storage: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Avoid exposure - obtain special instructions before use.Provide appropriate exhaust ventilation at places where dust is formed. For precautions see section 2.2. Store in cool place. Keep container tightly closed in a dry and well-ventilated place.

  • Exposure controls/personal protection:Occupational Exposure limit valuesBiological limit values Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday. Eye/face protection Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). Skin protection Wear impervious clothing. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace. Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique(without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands. The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and the standard EN 374 derived from it. Respiratory protection Wear dust mask when handling large quantities. Thermal hazards

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  • Manufacture/Brand:Usbiological
  • Product Description:Sofosbuvir
  • Packaging:1mg
  • Price:$ 418
  • Delivery:In stock
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  • Manufacture/Brand:DC Chemicals
  • Product Description:Sofosbuvir(PSI7977,GS-7977) 99.90%
  • Packaging:250 mg
  • Price:$ 400
  • Delivery:In stock
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  • Manufacture/Brand:DC Chemicals
  • Product Description:Sofosbuvir(PSI7977,GS-7977) 99.90%
  • Packaging:1 g
  • Price:$ 800
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  • Manufacture/Brand:Chemtos
  • Product Description:Sofosbuvirlabeled13Cd3
  • Packaging:25 mg
  • Price:$ 3990
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  • Manufacture/Brand:ChemScene
  • Product Description:Sofosbuvir 99.97%
  • Packaging:1g
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  • Manufacture/Brand:ChemScene
  • Product Description:Sofosbuvir 99.97%
  • Packaging:100mg
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  • Manufacture/Brand:ChemScene
  • Product Description:Sofosbuvir 99.97%
  • Packaging:50mg
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  • Manufacture/Brand:ChemScene
  • Product Description:Sofosbuvir 99.97%
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  • Manufacture/Brand:ChemScene
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  • Manufacture/Brand:ChemScene
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Relevant articles and documentsAll total 30 Articles be found

Mechanism-Based Solution to the ProTide Synthesis Problem: Selective Access to Sofosbuvir, Acelarin, and INX-08189

Simmons, Bryon,Liu, Zhuqing,Klapars, Artis,Bellomo, Ana,Silverman, Steven M.

, p. 2218 - 2221 (2017)

A general and efficient method for the synthesis of pronucleotide (ProTide) 5'-phosphoramidate monoesters is reported. This method consists of a highly stereoselective 5'-phosphorylation mediated by dimethylaluminum chloride to afford the desired target ProTides in excellent yields without employing 3'-protection strategies. The application of this methodology to the synthesis of a number of pharmaceutically relevant compounds currently marketed or under investigation in clinical research is demonstrated.

Method for synthesizing Sofosbuvir

-

Paragraph 0030-0067, (2020/04/17)

The invention discloses a method for synthesizing Sofosbuvir. The method comprises the steps of adding a compound 1, a compound 2 and dichloromethane into a reaction bulb, cooling the temperature to 0DEG C, then, adding aluminum chloride, adding a proper amount of pyridine, and carrying out a reaction at a reaction temperature of 15 DEG C to 20 DEG C, thereby producing the Sofosbuvir. According to the method, the reaction is high in conversion ratio and good in regioselectivity and stereoselectivity, so that the synthesis cost of the Sofosbuvir is reduced, and the method has remarkable socialand economic benefits.

PROCESS FOR THE PREPARATION OF (Sp)-SOFOSBUVIR AND INTERMEDIATES THEREOF

-

Page/Page column 13; 14, (2018/03/28)

The present invention is directed towards process for preparation of an optically pure (Sp)-Sofosbuvir of Formula-(I) and its intermediate namely (Sp)-isomer of isopropyl alanyl phosphoramidate of Formula (III) thereof.

Process route upstream and downstream products

Process route

2'-deoxy-2'-fluoro-2'-methyluridine
863329-66-2,2041584-99-8

2'-deoxy-2'-fluoro-2'-methyluridine

(S)-2-[(S)-((2,3,4,5,6-pentafluorophenoxy)(phenoxy)phosphoryl)amino]propionic acid isopropyl ester
1334513-02-8,1627824-09-2

(S)-2-[(S)-((2,3,4,5,6-pentafluorophenoxy)(phenoxy)phosphoryl)amino]propionic acid isopropyl ester

Conditions
Conditions Yield
With pyridine; aluminum (III) chloride; In dichloromethane; at 20 ℃; Reagent/catalyst; Temperature;
97.5%
With 2,6-dimethylpyridine; dimethylaluminum chloride; In tetrahydrofuran; hexane; at 0 - 45 ℃; for 20h;
86%
2'-deoxy-2'-fluoro-2'-methyluridine; With 3,3-diphenyl-2-propenal; tert-butylmagnesium chloride; In tetrahydrofuran; at -5 - 5 ℃; for 19h; Inert atmosphere;
(S)-2-[(S)-((2,3,4,5,6-pentafluorophenoxy)(phenoxy)phosphoryl)amino]propionic acid isopropyl ester; In tetrahydrofuran; Reagent/catalyst;
86.2%
With tert-butylmagnesium chloride; In tetrahydrofuran; water; at -5 - 5 ℃; Solvent;
83.3%
2'-deoxy-2'-fluoro-2'-methyluridine; With tert-butylmagnesium chloride; In tetrahydrofuran; at -5 - 20 ℃;
(S)-2-[(S)-((2,3,4,5,6-pentafluorophenoxy)(phenoxy)phosphoryl)amino]propionic acid isopropyl ester; In tetrahydrofuran; at -5 - 5 ℃; optical yield given as %de;
68%
2'-deoxy-2'-fluoro-2'-methyluridine; With tert-butylmagnesium chloride; In tetrahydrofuran; at -5 - 20 ℃; for 3h; Inert atmosphere;
(S)-2-[(S)-((2,3,4,5,6-pentafluorophenoxy)(phenoxy)phosphoryl)amino]propionic acid isopropyl ester; With Isopropyl acetate; In tetrahydrofuran; at 0 - 7 ℃; for 20h; Inert atmosphere;
68%
2'-deoxy-2'-fluoro-2'-methyluridine; With TurboGrignard; In tetrahydrofuran; at -10 - 5 ℃; for 2h; Inert atmosphere;
(S)-2-[(S)-((2,3,4,5,6-pentafluorophenoxy)(phenoxy)phosphoryl)amino]propionic acid isopropyl ester; In tetrahydrofuran; at -5 ℃; for 25h; Inert atmosphere;
53%
2'-deoxy-2'-fluoro-2'-methyluridine; With tert-butylmagnesium chloride; In tetrahydrofuran; at -5 - 20 ℃; for 2h;
(S)-2-[(S)-((2,3,4,5,6-pentafluorophenoxy)(phenoxy)phosphoryl)amino]propionic acid isopropyl ester; In tetrahydrofuran; at 5 ℃; for 21h;
27 g
With tert-butylmagnesium chloride; In tetrahydrofuran; acetonitrile; at 10 - 20 ℃; Inert atmosphere;
48 g
2'-deoxy-2'-fluoro-2'-methyluridine
863329-66-2,2041584-99-8

2'-deoxy-2'-fluoro-2'-methyluridine

(S)-2-[(S)-(4-nitro-phenoxy)-phenoxy-phosphorylamino]propionic acid isopropyl ester
1256490-31-9

(S)-2-[(S)-(4-nitro-phenoxy)-phenoxy-phosphorylamino]propionic acid isopropyl ester

Conditions
Conditions Yield
2'-deoxy-2'-fluoro-2'-methyluridine; With tert-butylmagnesium chloride; In tetrahydrofuran; at 20 ℃; for 1h;
(S)-2-[(S)-(4-nitro-phenoxy)-phenoxy-phosphorylamino]propionic acid isopropyl ester; In tetrahydrofuran; at 20 ℃; for 48h;
67.6%
2'-deoxy-2'-fluoro-2'-methyluridine; With tert-butylmagnesium chloride; In tetrahydrofuran; at 20 - 50 ℃; for 21h;
(S)-2-[(S)-(4-nitro-phenoxy)-phenoxy-phosphorylamino]propionic acid isopropyl ester; In tetrahydrofuran; at 20 ℃; for 60.25h;
40%
2'-deoxy-2'-fluoro-2'-methyluridine; With 1-methyl-pyrrolidin-2-one; In tetrahydrofuran; for 0.166667h;
With tert-butylmagnesium chloride; In tetrahydrofuran; at 20 ℃; for 0.166667h;
(S)-2-[(S)-(4-nitro-phenoxy)-phenoxy-phosphorylamino]propionic acid isopropyl ester; at 55 ℃; for 2.5h;
2'-deoxy-2'-fluoro-2'-methyluridine
863329-66-2,2041584-99-8

2'-deoxy-2'-fluoro-2'-methyluridine

C<sub>18</sub>H<sub>17</sub>F<sub>5</sub>NO<sub>5</sub>P
1627824-09-2

C18H17F5NO5P

Conditions
Conditions Yield
2'-deoxy-2'-fluoro-2'-methyluridine; C18H17F5NO5P; With N-ethyl-N,N-diisopropylamine; magnesium chloride; In tetrahydrofuran; at 30 - 40 ℃;
With hydrogenchloride; In tetrahydrofuran; water; for 0.5h; Reagent/catalyst; Temperature; Solvent;
88%
2'-deoxy-2'-fluoro-2'-methyluridine; With tert-butylmagnesium chloride; In tetrahydrofuran; at -5 - 30 ℃; for 1h; Inert atmosphere;
C18H17F5NO5P; In tetrahydrofuran; at 10 - 15 ℃;
67.5%
(S)-2-{[(1R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yI)-4-(R)-fluoro-3-(4-oxopentanoyl)-4-methyl-tetrahydrofuran-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid (S)-isopropyl ester

(S)-2-{[(1R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yI)-4-(R)-fluoro-3-(4-oxopentanoyl)-4-methyl-tetrahydrofuran-2-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid (S)-isopropyl ester

Conditions
Conditions Yield
With sodium sulfite; In tetrahydrofuran; water; at 20 ℃; for 4h;
100%
C<sub>22</sub>H<sub>31</sub>FN<sub>3</sub>O<sub>9</sub>P

C22H31FN3O9P

Conditions
Conditions Yield
With manganese(IV) oxide; In toluene; at 20 ℃; for 2h;
85%
2'-deoxy-2'-fluoro-2'-methyluridine
863329-66-2,2041584-99-8

2'-deoxy-2'-fluoro-2'-methyluridine

C<sub>17</sub>H<sub>20</sub>ClN<sub>2</sub>O<sub>5</sub>P

C17H20ClN2O5P

Conditions
Conditions Yield
With N-ethyl-N,N-diisopropylamine; zinc(II) chloride; In tetrahydrofuran; water; at 55 ℃; for 20h; Reagent/catalyst; Concentration;
80%
2'-deoxy-2'-fluoro-2'-methyluridine
863329-66-2,2041584-99-8

2'-deoxy-2'-fluoro-2'-methyluridine

(S)-2-[(S)-(2,3,4,5,6-pentafluoro-phenoxy)-phenoxy-phosphorylamino]propionic acid isopropyl ester
1337529-56-2,1627824-09-2

(S)-2-[(S)-(2,3,4,5,6-pentafluoro-phenoxy)-phenoxy-phosphorylamino]propionic acid isopropyl ester

Conditions
Conditions Yield
2'-deoxy-2'-fluoro-2'-methyluridine; With magnesium chloride; In tetrahydrofuran; at 25 - 30 ℃; for 2h; Inert atmosphere;
(S)-2-[(S)-(2,3,4,5,6-pentafluoro-phenoxy)-phenoxy-phosphorylamino]propionic acid isopropyl ester; In tetrahydrofuran; at 25 - 30 ℃; Reagent/catalyst;
80%
(S)-isopropyl 2-((S)-(((2R,3R,4R,5R)-5-(4-(benzoylamino)-2-oxopyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyl)tetrahydrofuran-2ylmethoxy)(phenoxy) phosphorylamino)propanoate

(S)-isopropyl 2-((S)-(((2R,3R,4R,5R)-5-(4-(benzoylamino)-2-oxopyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyl)tetrahydrofuran-2ylmethoxy)(phenoxy) phosphorylamino)propanoate

Conditions
Conditions Yield
With water; acetic acid; In tetrahydrofuran; for 5h; Reflux;
65%
With acetic acid; In water; at 90 - 95 ℃;
3 g
With citric acid; In 1,2-dimethoxyethane; water; at 75 - 80 ℃; Temperature;
3.6 g
bromo sofosbuvir

bromo sofosbuvir

Conditions
Conditions Yield
With 5%-palladium/activated carbon; In isopropyl alcohol; at 20 - 25 ℃; for 10h; under 2250.23 Torr; Solvent; Reagent/catalyst; Temperature; Pressure;
1.8 g
2'-deoxy-2'-fluoro-2'-methyluridine
863329-66-2,2041584-99-8

2'-deoxy-2'-fluoro-2'-methyluridine

(S)-2-((S)-(4-trifluoromethoxyphenoxy)phenoxyphosphorylamino)isopropyl propionate

(S)-2-((S)-(4-trifluoromethoxyphenoxy)phenoxyphosphorylamino)isopropyl propionate

Conditions
Conditions Yield
With tert-butylmagnesium chloride; In tetrahydrofuran; at 0 - 20 ℃; Inert atmosphere;
38%

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