[H-].[Na+].[NH:3]1[C:7]2=[N:8][CH:9]=[CH:10][CH:11]=[C:6]2[CH:5]=[C:4]1[CH:12]=[O:13].Br[CH2:15][CH:16]1[CH2:18][CH2:17]1>CN(C)C=O.C(Cl)Cl>[CH:16]1([CH2:15][N:3]2[C:7]3=[N:8][CH:9]=[CH:10][CH:11]=[C:6]3[CH:5]=[C:4]2[CH:12]=[O:13])[CH2:18][CH2:17]1A solution of sodium hydride (60.2 mg, 1.51 mmol) in N,N-dimethylformamide (20 mL) was stirred at 0° C. for 10 min. 1H-Pyrrolo[2,3-b]pyridine-2-carbaldehyde (200 mg, 1.37 mmol) was added and the mixture was stirred at 0° C. for 30 min and at it for 30 min. (Bromomethyl)cyclopropane (0.16 mL, 1.64 mmol available, for example, from Alfa Aesar) was added and the resulting mixture was stirred at 0° C. for 30 min and at it for 21 h. Reaction mixture was quenched by the addition of water (50 mL). After addition of Et2O (50 mL), the layers were separated. The aqueous layer was further extracted with Et2O (2×50 mL) and the combined organic layers were washed with H2O (2×35 mL). The organic phase was dried through a hydrophobic frit and concentrated under reduced pressure to give a brown oil which was loaded in DCM on a 50 g SNAP silica cartridge and purified by SP4, eluting with a gradient of 0-20% ethyl acetate/cyclohexane (15CV). The appropriate fractions were combined and evaporated under reduced pressure to give the required product 1-(cyclopropylmethyl)-1H-pyrrolo[2,3-b]pyridine-2-carbaldehyde (201 mg, 73.4%) as a colourless oil.
Loading…
