6-Bromoimidazo[1,2-a]pyridine-2-methanol

Intermediate 53 was prepared according to an analogous procedure as described for the synthesis of intermediate 43, using intermediate 52 as starting material. The reaction mixture was stirred at rt for 1 h, then evaporated under vacuum. The residue was neutralized with a IN aqueous solution of HC1 and extracted with DCM (x2). The mixture was filtered on a glass frit to give 348 mg (17%;, off-white solid) of intermediate 29. The filtrate was transferred in a separatory funnel, the organic layer was separated and the aqueous layer was extracted with DCM (x2). The combined organic layers were dried over MgSO4, filtered and evaporated under vacuum to give 1.34 g (67%, off- white solid) of intermediate 53. The product (84%;, global yield) was used without purification in the next step.Intermediate 54 was prepared according to an analogous procedure as described for the synthesis of intermediate 44, using intermediate 53 as starting material. Only DMF was used as solvent. The reaction mixture was stirred at rt for 18 h. The residue (2.96 g) was purified by chromatography over silica gel (Regular SiOH 30 muiotaeta; 200 g; gradient: from 100% DCM to 90% DCM, 10% EtOAc). The pure fractions were collected and the solvent was evaporated to give 2.11 g (84%) of intermediate 54.Intermediate 38 (66.1 mg, 0.44 mmol) and (6-bromoimidazo[1 , 2-a]pyridin-2-yl)- methanol (100 mg, 0.44 mmol) were dissolved in acetonitrile (10 mL) and pyridiniumptoluenesulfonate (443 mg, 1.76 mmol) was added. The resulting mixture was heated at 80C overnight. The resulting mixture was cooled and evaporated onto silica. Purification by column chromatography (0-15% MeOH in DCM) gave a clear oil, whichwas freeze-dried to give the title compound (50 mg, 32%), 7:3 mixture of diastereomers, as a white solid.Major diastereomer (trans): H (400 MHz, DMSO-d6) 7.80 (dd, 1H, J0.6, 1.9 Hz), 7.57 (dd, 1H, J0.6, 8.8 Hz), 7.48 (m, 1H), 7.42 (m, 1H), 7.36 (dd, 1H, J9.5, 1.9 Hz), 7.29 (t, 1H, J7.3 Hz), 7.04 (d, 1H, J7.4 Hz), 6.97 (d, 1H, J2.5 Hz), 5.63 (qd, 1H, J6.3, 2.6 Hz), 5.22 (t, 1H, J5.7 Hz), 4.54 (m, 2H), 1.52 (d, 3H, J6.3 Hz.Minor diastereomer (cis): H (400 MHz, DMSO-d6) 7.78 (m, 1H), 7.57 (m, 1H), 7.48 (m, 1H), 7.42 (m, 1H), 7.36 (dd, 1H, J9.5, 1.9 Hz), 7.30 (t, 1H, J7.3 Hz), 6.92 (m, 1H), 6.82 (d, 1H, J2.8 Hz), 5.40 (m, 1H), 5.28 (t, 1H, J5.7 Hz), 4.66 (d, 2H, J5.6 Hz), 1.66 (d, 3H, J6.4 Hz). LCMS MH m/z 359.60.

Molecular Weight:227.06
XLogP3:1.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:225.97418
Monoisotopic Mass:225.97418
Topological Polar Surface Area:37.5
Heavy Atom Count:12
Complexity:167
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes