Method for producing indole compound
The present invention aims to provide a new method for producing an indole compound or a salt thereof, which has an ITK inhibitory action, and is useful for the prophylaxis or treatment of inflammatory disease. The present invention is a method for producing N-[2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indol-6-yl]-N-methyl-(2S)-2-(morpholin-4-yl)propanamide, which comprises a step of reacting
1. A method of producing a compound of the formula [I]
which comprises a step of removing the protecting group from a compound of the formula [III]
to give a compound of the formula [I].
2. A method of producing a compound of the formula [II]
which comprises a step of removing the protecting group from a compound of the formula [III]
to give a compound of the formula [I], and
a step of treating a compound of the formula [I]
with hydrogen chloride to give a compound of the formula [II].
3. The method of claim 1 or 2 , which further comprises a step of reacting a compound of the formula [V]
with a compound of the formula [IV]
or a reactive derivative thereof or a salt thereof to give a compound of the formula [III]
4. The method of claim 3 , which further comprises a step of subjecting a compound of the formula [VI]
wherein R 1 and R 2 are each independently hydrogen, C 1-6 alkyl or C 1-6 alkoxy, to a reduction reaction to give a compound of the formula [V]
5. The method of claim 4 , which further comprises a step of reacting a compound of the formula [VII]
wherein R 1 is as defined in claim 4 ,
with a compound of the formula [XI]
wherein R 2 is as defined in claim 4 ,
to give a compound of the formula [VI]
wherein R 1 and R 2 are as defined above.
6. The method of claim 5 , which further comprises a step of subjecting a compound of the formula [VIII]
wherein R 1 is as defined in claim 4 ,
to tetrahydropyranylation to give a compound of the formula [VII]
wherein R 1 is as defined above.
7. The method of claim 6 , which further comprises a step of reacting a compound of the formula [IX]
with a compound of the formula [IX]
wherein
M is sodium or potassium, and
R 1 is as defined in claim 4 ,
to give a compound of the formula [VIII]
wherein R 1 is as defined above.
8. The method of claim 2 , which further comprises a step of purifying a compound of the formula [II]
with 1-propanol.