US8193379B2
Active / In Force
US
⏱️ 3.9 years remaining
Method for preparing 4B-amino-4′-demethyl-4-desoxypodophyllotoxin
Assignee: Individual
•
Filing: 2010-09-30
•
Granted: 2012-06-05
•
Expires: 2030-09-30
Abstract
Abstract The invention relates to a method for synthesizing 4β-amino-4′-demethyl-4-desoxypodophyllotoxin of formula (1), characterized by comprising the following successive steps: a) reacting, in a pure weak acid or in a mixture consisting of acid, water and of organic solvent, without another solvent, at a temperature higher than the ambient temperature, thiourea with 4β-halogenoacetamido-4′-demethyl-4-desoxypodophyllotoxin, and; b) recovering the 4β-amino-4′-demethyl-4-desoxypodophyllotoxin.
Inventors
- 👤 Yves Guminski
- 👤 Martial Grousseaud
- 👤 Thierry Imbert
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 07:30
CPC Classifications
C; C07; C07D; C07D493/00; C07D493/02; C07D493/04
Claims Analysis
Total Claims: 21
Claim 1
Independent Claim
85 words
A method for synthesizing a hydrohalide salt of 4β-amino-4′-demethyl-4-desoxypodophyllotoxin of Formula A: in which X represents a halogen atom selected form the group consisting of chlorine, bromine and iodine, comprising the following successive stages: i) reaction, in a mixture of acid, water and organic solvent, at a temperature greater than ambient temperature, of thiourea with 4β-halogenoacetamido-4′-demethyl-4-desoxypodophyllotoxin of Formula 3: in which X represents a halogen atom selected form the group consisting of chlorine, bromine and iodine; and ii) recovery of the hydrohalide salt of 4β-amino-4′-demethyl-4-desoxypodophyllotoxin.
Claim 2
Independent Claim
85 words
A method for synthesizing a hydrohalide salt of 4β-amino-4′-demethyl-4-desoxypodophyllotoxin of Formula A: in which X represents a halogen atom selected form the group consisting of chlorine, bromine and iodine, comprising the following successive stages: i) reaction, in a mixture of acid, water and organic solvent, at a temperature greater than ambient temperature, of thiourea with 4β-halogenoacetamido-4′-demethyl-4-desoxypodophyllotoxin of Formula 3: in which X represents a halogen atom selected form the group consisting of chlorine, bromine and iodine; and ii) recovery of the hydrohalide salt of 4β-amino-4′-demethyl-4-desoxypodophyllotoxin.
Claim 3
Dependent Claim
25 words
The method as claimed in claim 1 , wherein during stage i), the reaction medium is heated to a temperature between 60 and 100° C.
Claim 4
Dependent Claim
31 words
The method as claimed in claim 1 , wherein, during stage i), 4β-halogenoacetamido-4′-demethyl-4-desoxypodophyllotoxin is placed in contact with the mixture of acid, water and organic solvent prior to addition of thiourea.
Claim 5
Dependent Claim
17 words
The method as claimed in claim 1 , wherein the organic solvent is a hydrosoluble organic solvent.
Claim 6
Dependent Claim
25 words
The method as claimed in claim 4 , wherein the organic solvent is selected form the group consisting of cyclic ethers, alcohols, N,N-dimethylacetamide, dimethylformamide, N-methylpyrolidone.
Claim 7
Dependent Claim
17 words
The method as claimed in claim 5 , wherein the organic solvent is the cyclic ether dioxane.
Claim 8
Dependent Claim
16 words
The method as claimed in claim 5 , wherein the organic solvent is the alcohol ethanol.
Claim 9
Dependent Claim
15 words
The method as claimed in claim 1 , wherein the acid is a strong acid.
Claim 10
Dependent Claim
26 words
The method as claimed in claim 8 , wherein the strong acid is selected from the group consisting of hydrochloric acid, sulphuric acid and phosphoric acid.
Claim 11
Dependent Claim
15 words
The method as claimed in claim 1 , wherein the acid is a weak acid.
Claim 12
Dependent Claim
32 words
The method as claimed in claim 10 , wherein the weak acid is a carboxylic acid of formula 5: R—COOH, in which R represents hydrogen, or a C 1 -C 2 alkyl.
Claim 13
Dependent Claim
15 words
The method as claimed in claim 11 , wherein the weak acid is acetic acid.
Claim 14
Dependent Claim
14 words
The method as claimed in claim 5 , wherein the acid is acetic acid.
Claim 15
Dependent Claim
35 words
The method as claimed in claim 13 , wherein the organic solvent is selected from the group consisting of ethanol, dioxane N,N-dimethylacetamide, dimethylformide, and N-methylpyrrolidone, and a volumetric ratio of organic solvent/water/acetic acid is 5/1/1.
Claim 16
Dependent Claim
21 words
The method as claimed in claim 1 , wherein the molar ratio between 4β-halogenoacetamido-4′-demethyl-4-desoxypodophyllotoxin and thiourea is between 0.5 and 1.
Claim 17
Dependent Claim
51 words
The method as claimed in claim 1 , wherein the 4β-halogenoacetamido-4′-demethyl-4-desoxypodophyllotoxin of Formula 3 is obtained by reaction in an acid medium of 4′-demethylpipodophyllotoxin of Formula with a halogenoacetonitrile of Formula: 6X—CH 2 —C≡N, in which X represents a halogen atom selected from the group consisting of chlorine, bromine and iodine.
Claim 18
Dependent Claim
12 words
The method as claimed in claim 1 , wherein X is chlorine.
Claim 19
Dependent Claim
12 words
The method as claimed in claim 2 , wherein X is chlorine.
Claim 20
Dependent Claim
12 words
The method as claimed in claim 5 , wherein X is chlorine.
Claim 21
Dependent Claim
12 words
The method as claimed in claim 9 , wherein X is chlorine.
References Cited (Backward Citations)
FR2869035A1
Cited
US7932406B2
Cited
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