Method for producing 7h-pyrrolo[2, 3-d]pyrimidine derivative and intermediate thereof
The present invention provides a method for producing a 7H-pyrrolo[2,3-d]pyrimidine derivative that is useful as a janus kinase (JAK) inhibitor; an intermediate of the 7H-pyrrolo[2,3-d]pyrimidine derivative; and a method for producing the intermediate. The present invention provides a method for producing 3-[(3S,4R)-3-methyl-6-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,6-diazaspiro[3.4]octan-1-yl]-3-oxopropanenitrile, which uses a salt of an organic acid and (3S,4R)-3-methyl-1,6-diazaspiro[3.4]octane-1-carboxylic acid benzyl.
1. A disodium salt dihydrate of a compound of formula [10]
2. A crystal of a disodium salt dihydrate of a compound of formula [10]
showing a powder X-ray diffraction pattern having peaks at 4.9°±0.2°, 12.3°±0.2°, 15.0°±0.2°, 19.2°±0.2°, Of and 22.7°±0.2° of a diffraction angle (2θ) determined by using CuKα radiation.
3. A process for preparing a disodium salt dihydrate of a compound of formula [10]
comprising:
reacting a compound of formula [8]
with acid followed by treatment with aqueous sodium hydroxide.
4. The process of claim 3 , further comprising the step of reacting a compound of formula [7]
with halogenated acetic acid tert-butyl ester to give the compound of formula [8].
5. The process of claim 4 , further comprising the step of reacting a compound of formula [6]
or its salt with halogenated formic acid benzyl ester to give the compound of formula [7].
6. The process of claim 5 , further comprising the step of removing a protecting group from a compound of formula [4]
or its salt to give a compound of formula [6] or its salt.