Production method of imidazole derivatives
AssigneeTakeda Pharmaceutical Company Limited
InventorsYoichi Kawabata, Yasuhiro Sawai, Kazuaki Kanno, Naotaka Sawada
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Abstract
The present invention provides an advantageous production method of an imidazole derivative, which is suitable for industrial production. Compound (VI) is produced by reacting compound (I) with a Grignard reagent or a magnesium reagent, and a lithium reagent, and then reacting the resulting compound with compound (V).
Claims7
(canceled)
A method of producing 6-(7-hydroxy-6,7-dihydro-5H-5 pyrrolo[1,2-c]imidazol-7-yl)-N-methyl-2-naphthamide or a salt thereof, which comprises
- Step (1):
- a step of reacting a compound represented by the formula:
- wherein R1 is an iodine atom or a bromine atom,
- with a compound represented by the formula:
- R2—MgX (II)
- wherein R2 is a C1-6 alkyl group or a C6-12 aryl group;
- and X is a chlorine atom, a bromine atom or an iodine atom, or a compound represented by the formula:
- R2R2′—Mg (III)
- wherein R2′ is a C1-6 alkyl group or a C6-12 aryl group;
- and R2 is as defined above, and a compound represented by the formula:
- R3—Li (IV)
- wherein R3 is a C1-6 alkyl group or a C6-12 aryl group, and then reacting the resulting compound with a compound represented by the formula:
- wherein PG is a protecting group,
- or a salt thereof;
- Step (2):
- a step of subjecting a compound represented by the formula:
- wherein PG is as defined above,
- or a salt thereof, which is obtained in Step (1), to oxidation;
- Step (3):
- a step of reacting a compound represented by the formula:
- wherein PG is as defined above,
- or a salt thereof, which is obtained in Step (2), with a compound represented by the formula:
- BrZnCH2CO2—R4 (VIII)
- wherein R4 is a C1-6 alkyl group;
- Step (4):
- a step of subjecting a compound represented by the formula:
- wherein each symbol is as defined above,
- or a salt thereof, which is obtained in Step (3), to reduction;
- and
- Step (5):
- a step of subjecting a compound represented by the formula:
- wherein PG is as defined above,
- or a salt thereof, which is obtained in Step (4), to cyclization and deprotection.
A method of producing of a compound represented by the formula:
- wherein PG is a protecting group;
- and R4 is a C1-6 alkyl group, or a salt thereof, which comprises
- Step (3a):
- a step of reacting a compound represented by the formula:
- wherein PG is as defined above,
- or a salt thereof, with a compound represented by the formula:
- BrZnCH2CO2—R4 (VIII)
- wherein R4 is as defined above,
- and then adding citric acid to the obtained reaction mixture.
A method of producing of 6-(7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methyl-2-napht-hamide or a salt thereof, which comprises
- Step (3a):
- a step of reacting a compound represented by the formula:
- wherein PG is a protecting group,
- or a salt thereof, with a compound represented by the formula:
- BrZnCH2CO2—R4 (VIII)
- wherein R4 is a C1-6 alkyl group,
- and then adding citric acid to the obtained reaction mixture;
- Step (4):
- a step of subjecting a compound represented by the formula:
- wherein each symbol is as defined above,
- or a salt thereof, which is obtained in Step (3a), to reduction;
- and
- Step (5):
- a step of subjecting a compound represented by the formula:
- wherein PG is as defined above,
- or a salt thereof, which is obtained in Step (4), to cyclization and deprotection.
Dependencies are inferred from the claim text.