Assignment of NMR Data andConformational Analysis of Larotrectinib and its Precursors

Abstract NMR experiments were used to identify the two main conformations of Larotrectinib and its synthetic precursor, the nitro compound 4. Conformational analysis by dynamic NMR was performed in different temperature and solvents, combining 2D EXSY and NOE experiments. The results revealed the conformations of Larotrectinib and compound 4 were caused by the barrier to rotation of C11-N17. Meanwhile, the conformational specific structures of compound 4 were postulated based on NOE data and molecular simulation. The complete assignments of 1H and 13C NMR data for compounds 1, 4 and 5 are reported for the first time.