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US 2004/0167157 A1Published application
Process for preparation of amidine derivatives
AssigneeShionogi & Co., Ltd.
InventorsToshiaki Masui, Kyozo Kawata, Takayuki Kasai, Makoto Kaninuma
Life of this patent
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Abstract
A process for producing amidine derivatives represented by the following reaction scheme, characterized in that the reactions of steps 1 and 3 are conducted in acetonitrile and the reaction of step 2 is conducted in acetone. 1
Claims7
A process for producing a compound of the formula (II):
- 25
- wherein
- ring A represents a 5 to 9 membered alicyclic group, which may contain at least one of O, S, SO, SO2 and/or NR1 and may be substituted with at least one alkyl;
- R1 is hydrogen, alkyl, esterified carboxy, carbamoyl or acyl;
- R is optionally substituted aryl or optionally substituted aromatic heterocyclic group;
- and
- Hal is a halogen, comprising
- Step 1, wherein a compound of the formula (v):
- 26
- wherein
- R10 is optionally substituted aryl, optionally substituted aromatic heterocyclic group, optionally substituted alkyl, or optionally substituted cycloalkyl;
- and ring A is as defined above,
- is reacted with a halogenating agent in acetonitrile in the presence of dimethylformamide and then hydrolyzed to obtain a compound of the formula (IV):
- 27
- wherein ring A is as defined above, and Hal is a halogen,
- Step 2, wherein the resultant compound (IV) is reacted with a compound of the formula R—COR11, wherein R is optionally substituted aryl or optionally substituted aromatic heterocyclic group, and R11 is hydroxy or halogen, in acetone in the presence of an organic base and optionally further a halogenating agent to obtain a compound of the formula (III):
- 28
- wherein ring A, Hal and R are as defined above, and
- Step 3, wherein the obtained compound of the formula (III) is reacted with a halogenating agent in acetonitrile in the presence of an organic base and then aminated.
16 more elements
A process for producing a compound of the formula (IV):
- 29
- wherein
- ring A represents a 5 to 9 membered alicyclic group, which may contain at least one of O, S, SO, SO2 and/or NR1 and may be substituted with at least one alkyl;
- and
- R1 is hydrogen, alkyl, esterified carboxy, carbamoyl or acyl;
- Hal is a halogen, comprising that a compound of the formula (V):
- 30
- wherein
- R10 is optionally substituted aryl, optionally substituted aromatic heterocyclic group, optionally substituted alkyl, or optionally substituted cycloalkyl;
- and ring A is as defined above,
- is reacted with a halogenating agent in acetonitrile in the presence of dimethylformamide and then hydrolyzed.
8 more elements
A process for producing a compound of the formula (III):
- 31
- wherein
- ring A represents a 5 to 9 membered alicyclic group, which may contain at least one of O, S, SO, SO2 and/or NR1 and may be substituted with at least one alkyl;
- R1 is hydrogen, alkyl, esterified carboxy, carbamoyl or acyl;
- R is optionally substituted aryl or optionally substituted aromatic heterocyclic group;
- and
- Hal is a halogen, comprising that a compound (IV):
- 32
- wherein ring A, and Hal are as defined above, is reacted with a compound of the formula R-COR11, wherein R is as defined above and R11 is hydroxy or halogen, in the presence of an organic base and optionally further a halogenating agent.
6 more elements
A process for producing a compound of the formula (II):
- 33
- wherein
- ring A represents a 5 to 9 membered alicyclic group, which may contain at least one of O, S, SO, SO2 and/or NR1 and may be substituted with at least one alkyl;
- R1 is hydrogen, alkyl, esterified carboxy, carbamoyl or acyl;
- R is optionally substituted aryl or optionally substituted aromatic heterocyclic group;
- and
- Hal is a halogen, comprising that a compound of the formula (III):
- 34
- wherein ring A, R and Hal are as defined above, is reacted with a halogenating agent in acetonitrile in the presence of an organic base and then aminated.
6 more elements
A process for producing a compound of the formula (I):
- 35
- wherein
- ring A represents a 5 to 9 membered alicyclic group, which may contain at least one of O, S, SO, SO2 and/or NR1 and may be substituted with at least one alkyl;
- R1 is hydrogen, alkyl, esterified carboxy, carbamoyl or acyl;
- R is optionally substituted aryl or optionally substituted aromatic heterocyclic group, comprising
- Step 1, wherein a compound of the formula (V):
- 36
- wherein
- R10 is optionally substituted aryl, optionally substituted aromatic heterocyclic group, optionally substituted alkyl, or optionally substituted cycloalkyl;
- and ring A is as defined above,
- is reacted with a halogenating agent in acetonitrile in the presence of dimethylformamide and then hydrolyzed to obtain
- a compound of the formula (IV):
- 37
- wherein ring A is as defined above, and Hal is a halogen,
- Step 2, wherein the compound (IV) obtained is reacted with a compound of the formula R—COR11, wherein R is optionally substituted aryl or optionally substituted aromatic heterocyclic group, and R11 is hydroxy or halogen, in the presence of an organic base and optionally a halogenating agent to obtain a compound of the formula (III):
- 38
- wherein ring A, Hal and R are as defined above,
- Step 3, wherein the obtained compound of the formula (III) is reacted with a halogenating agent in acetonitrile in the presence of an organic base and then aminated to obtain a compound of the formula (II):
- 39
- wherein ring A, Hal and R are as defined above, and
- Step 4, wherein the obtained compound of the formula (II) is reacted in the presence of a sulfinate.
18 more elements
Dependencies are inferred from the claim text.