ChemicalBook CAS DataBase List Tenofovir disoproxil fumarate

Tenofovir disoproxil fumarate synthesis

7synthesis methods

Product Name:Tenofovir disoproxil fumarate
CAS Number:202138-50-9
Molecular formula:C23H34N5O14P
Molecular Weight:635.52

35180-01-9
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$5.00/5g

110-17-8 Synthesis

110-17-8
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$9.00/5g

147127-20-6
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$5.00/1g

202138-50-9
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$5.00/100mg

Yield:202138-50-9 90%

Reaction Conditions:

Stage #1: tenofovirwith triethylamine in 1-methyl-pyrrolidin-2-one at 63; for 0.5 h;
Stage #2: chloromethyl isopropyl carbonate in 1-methyl-pyrrolidin-2-one at 63; for 4 h;
Stage #3: (2E)-but-2-enedioic acid in isopropyl alcohol at 50; for 0.5 h;Concentration;

Steps:

1

In a tenofovir (PMPA) 4.0g prepared in Example 1 was added to the kettle and N- methylpyrrolidone 15 and triethylamine 5.8. The reaction solution was heated to about 63 and stirred for 30 minutes In the chloromethyl isopropyl carbonate 10gAnd then stirred for 4 hours at this temperature. After cooling the reaction solution to room temperature and again it cooled to 5°C ,Below 15°C cold water were added to maintain 25ml. At 15°C stirred for one hour, And extracted twice with methylene chloride 15ml.After washing twice, the organic layer was then partitioned with water 10ml and the organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure to give the remaining filtrate tenofovir disoproxil (TD) as an oil.The tenofovir disoproxil (TD) of the oil phase Isopropyl alcohol 35ml And 1.6g of fumaric acid Added and the temperature was raised to about 50°C Dong was completely dissolved for 30 minutes.Then slowly cooled to about 25 the reaction solution was cooled, dissolved again in 3 was stirred for 4 hours and kept at this temperature.Crystals were filtered and washed with isopropyl alcohol and then dried in vacuo at about 40 10 desired compound of tenofovir disoproxil fumarate (TDF), 4.7g (yield: 53%) was obtained.The obtained tenofovir disoproxil fumarate (TDF) in 4.7g In the 40ml and isopropyl alcohol and heated to about 50°C Open completely dissolved during 30 minutes.Then slowly cooled to about 25°C the reaction solution was cooled, dissolved again in 3°C kept at said temperature and stirred for 4 hours.Crystals were filtered, washed with isopropyl alcohol 100 mland vacuum-dried at about 40°C tenofovir disoproxil fumarate (TDF), 4.3g (Yield: 90%) of the crystal form was obtained.

References:

KR2016/38627,2016,A Location in patent:Paragraph 0121; 0122; 0123; 0124