(R)-3-Pyrrolidinol → (R)-1-(2-(4-chloro-3,5-diphenyl-1H-pyrazolo[3,4-c]pyridazin-1-yl)ethyl)pyrrolidin-3-ol
Reaction equation
[NH:1]1[CH2:5][CH2:4][C@@H:3]([OH:6])[CH2:2]1.[Cl:7][C:8]1[C:13]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[N:12][N:11]=[C:10]2[N:20]([CH2:29][CH2:30]I)[N:21]=[C:22]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:9]=12>C(Cl)Cl>[Cl:7][C:8]1[C:13]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[N:12][N:11]=[C:10]2[N:20]([CH2:29][CH2:30][N:1]3[CH2:5][CH2:4][C@@H:3]([OH:6])[CH2:2]3)[N:21]=[C:22]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:9]=12Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
A solution of (R)-3-pyrrolidinol (166 mg, 1.9 mmol) in CH2Cl2 (1.5 ml) was added to 4-chloro-1-(2-iodoethyl)-3,5-diphenyl-1H-pyrazolo[3,4-c]pyridazine (example 74 step 1) (113 mg, 0.24 mmol) and the reaction stirred at ambient for 24 h. The resultant residue was purified using chromatography (silica gel, gradient 20 to 100% ethyl acetate/isohexane, then 0 to 100% ethyl acetate/acetone) followed by preparative HPLC to give Compound 83 as an orange solid (17 mg).