Triethylamine → 7-[(5-methoxypyridin-2-yl)acetyl]-2-[(1R)-5-(4-methyl-1H-pyrazol-1-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane

To a mixture of (5-methoxypyridin-2-yl)acetic acid (SM-1aa, 25.9 mg, 0.16 mmol) in dichloromethane (5 mL) was added 1,1′-carbonyldiimidazole (25.9 mg, 0.16 mmol) and the reaction was stirred overnight at room temperature. In a separate flask, to a mixture of 2-((R)-5-(4-methyl-1H-pyrazol-1-yl)-2,3-dihydro-1H-inden-1-yl)-2,7-diazaspiro[3.5]nonane dihydrochloride (8-1b, 60.0 mg, 0.15 mmol) in dichloromethane (10 mL) was added triethylamine (0.31 mL, 0.23 mmol). The activated acid was then added to the amine solution and the resulting mixture was stirred at room temperature for 2 hours. The reaction was concentrated and purified on an ISCO (Teledyne Isco Inc., Lincoln Nebr.) 12 g silica column eluting with 50-100% MeOH in ethyl acetate gradient to give 26 mg (36%) of the title compound (8A) as a gum. MS (ES+) 472.9 (M+H)+. 1H NMR (CD3OD) δ 1.62-1.75 (m, 4H), 1.85-1.97 (m, 1H), 2.13 (s, 3H), 2.17-2.31 (m, 1H), 2.80-2.92 (m, 1H), 3.03-3.15 (m, 1H), 3.20-3.27 (m, 2H), 3.32 (d, 2H), 3.48-3.56 (m, 4H), 3.84 (s, 3H), 3.85 (s, 2H), 4.03 (dd, 1H), 7.22-7.28 (m, 1H), 7.35 (dd, 1H), 7.38-7.44 (m, 1H), 7.44-7.51 (m, 2H), 7.55 (s, 1H), 7.94 (s, 1H), 8.13 (d, 1H).

1. stirringthe resulting mixture was stirred at room temperature for 2 hours
2. concentrationThe reaction was concentrated
3. custompurified on an ISCO (Teledyne Isco Inc., Lincoln Nebr.) 12 g silica column
4. washeluting with 50-100% MeOH in ethyl acetate gradient

ORD-Eintrag

ord-358c5aac27744f789013c874790813cb

Quelldatensatz

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08609680B2