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 treating a compound of the formula [I]
with hydrogen chloride to give a compound of the formula [II].
3 . 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].
4 . The method of claim 1 or 3 , 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]
5 . The method of claim 4 , 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]
6 . The method of claim 5 , which further comprises a step of reacting a compound of the formula [VII]
with a compound of the formula [XI]
to give a compound of the formula [VI]
7 . The method of claim 6 , which further comprises a step of subjecting a compound of the formula [VIII]
to tetrahydropyranylation to give a compound of the formula [VII]
8 . The method of claim 7 , which further comprises a step of reacting a compound of the formula [IX]
with a compound of the formula [X]
wherein
M is sodium or potassium,
to give a compound of the formula [VIII]
9 . The method of claim 2 or 3 , which further comprises a step of purifying a compound of the formula [II]
with 1-propanol.
10 . (canceled)
11 . A compound of the formula [V]
12 . A compound of the formula [III]
13 . 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.
14 . A compound of the formula [VII]
wherein R 1 is hydrogen, C 1-6 alkyl or C 1-6 alkoxy.
15 . A compound of the formula [VIII]
wherein R 1 is hydrogen, C 1-6 alkyl or C 1-6 alkoxy.
16 . A compound of the formula [XI]
wherein R 2 is hydrogen, C 1-6 alkyl or C 1-6 alkoxy.