Pyridine → N-(5-methylpyrazin-2-yl)-3-[(phenylmethyl)oxy]-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide

Oxalyl chloride (1.9 mL, 22.2 mmol) and DMF (1 drop) were added to a solution of 3-[(phenylmethyl)oxy]-5-[(3S)-tetrahydrofuran-3-yloxy]benzoic acid (5.8 g, 18.5 mmol) in DCM (100 mL) and the mixture stirred at RT for 16 hours. The mixture was evaporated in vacuo to a residue which was redissolved in DCM (25 mL) and added to a stirred mixture of 2-amino-5-methylpyrazine (2.22 g, 20.35 mmol) and pyridine (1.81 mL, 22.2 mmol) in DCM (100 mL) at 5° C.-10° C. The mixture was stirred at RT for 18 hours, the DCM evaporated in vacuo to give a residue which was partitioned between water (50 mL) and ethyl acetate (125 mL). The organic layer was washed with brine, dried (MgSO4) and evaporated to a residue which was chromatographed on silica, eluting with 60% ethyl acetate in isohexane, to give the desired material (5.1 g). 1H NMR δ (CDCl3): 2.1-2.2 (m, 2H), 2.5 (s, 3H), 3.8-3.95 (m, 4H), 4.9 (m, 1H), 5.0 (s, 2H), 6.6 (s, 1H), 6.95 (s, 1H), 7.05 (s, 1H), 7.35 (m, 5H), 8.05 (s, 1H), 8.3 (s, 1H), 9.5 (s, 1H); m/z 406 (M+H)+.

1. customThe mixture was evaporated in vacuo to a residue which
2. dissolutionwas redissolved in DCM (25 mL)
3. stirringThe mixture was stirred at RT for 18 hours
4. customthe DCM evaporated in vacuo
5. customto give a residue which
6. customwas partitioned between water (50 mL) and ethyl acetate (125 mL)
7. washThe organic layer was washed with brine
8. dry with materialdried (MgSO4)
9. customevaporated to a residue which
10. customwas chromatographed on silica
11. washeluting with 60% ethyl acetate in isohexane

ORD-Eintrag

ord-b5e11a45ead644c9ae5297b4bcb52f61

Quelldatensatz

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07943607B2