[Cl:1][C:2]1[C:7]([Cl:8])=[C:6](I)[CH:5]=[CH:4][N:3]=1.Cl.[NH:11]1[CH2:16][CH2:15][C:14]2([C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[CH2:18][O:17]2)[CH2:13][CH2:12]1.CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>CC#N>[Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([N:11]2[CH2:16][CH2:15][C:14]3([C:24]4[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=4[CH2:18][O:17]3)[CH2:13][CH2:12]2)[CH:5]=[CH:4][N:3]=1A mixture of D10 (1 g, 3.655 mmol), spiro[isobenzofuran-1(3H),4′-piperidine], hydrochloride [CAS 37663-44-8] (0.83 g, 4.386 mmol) and DIPEA (1.273 ml, 7.309 mmol) in CH3CN (9 ml) was heated in a sealed tube at 110° C. for 16 h. The mixture was then treated with NaHCO3 (aqueous sat. solution) and extracted with EtOAc. The organic layer was separated, dried (Na2SO4) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel; DCM/EtOAc up to 2% as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate compound D21 (0.199 g, 16%) as a white solid. M.P. 160.8° C.
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