(3S,4S)-4-[(S)-3-(4-Fluoro-benzyl)-piperidin-1-ylmethyl]-tetrahydro-pyran-3-ylamine → 1-{(3S,4S)-4-[(S)-3-(4-fluorobenzyl)-piperidin-1-ylmethyl]-tetrahydro-pyran-3-yl}-3-[3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-urea

(3S,4S)-4-[(S)-3-(4-Fluoro-benzyl)-piperidin-1-ylmethyl]-tetrahydro-pyran-3-ylamine (44 mg, 143 μmol) and [3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-carbamic acid phenyl ester (47 mg, 158 μmol) were dissolved in acetonitrile (1 mL) and the mixture was stirred at room temperature. After 24 h , the mixture was concentrated, dissolved in ethyl acetate, washed with water, dried (Na2SO4) and concentrated. The residue was purified by reverse phase high pressure liquid chromatography (C18, 10-100% acetonitrile in water, containing 0.05% trifluoroacetic acid), then by flash column chromatography (5% methanol in dichloromethane, containing 0.5% ammonium hydroxide) to provide the product as a glass (16 mg, 23%). 1H NMR (300 mHz, CD3OD) δ7.95 (s, 1H), 7.52 (m, 2H), 7.43 (m, 1H), 7.05 (m, 2H), 6.86 (m, 2H), 4.19 (s, 3H), 3.94 (dd, J=10.7, 4.4 Hz, 1H), 3.87 (bd, 1H), 3.50 (td, J=9.9, 4.4 Hz, 1H), 3.39 (m, 1H), 3.09 (t, J=10.2 Hz, 1H), 2.93 (bd, 1H), 2.85 (bd, 1H), 2.56 (dd, J=12.8, 5.2 Hz, 1H), 2.45 (m, 2H), 2.30 (dd, J=12.4, 6.6 Hz, 1H), 2.04 (bt, 1H), 1.9-1.5 (7H), 1.40 (m, 1H), 0.95 (m, 1H), ESI MS: (M+H)+=508.3 (100%).

1. concentrationthe mixture was concentrated
2. dissolutiondissolved in ethyl acetate
3. washwashed with water
4. dry with materialdried (Na2SO4)
5. concentrationconcentrated
6. customThe residue was purified by reverse phase high pressure liquid chromatography (C18, 10-100% acetonitrile in water, containing 0.05% trifluoroacetic acid)
7. additionby flash column chromatography (5% methanol in dichloromethane, containing 0.5% ammonium hydroxide)

ORD-Eintrag

ord-1c53cbd86c7543baaf1398d457bc0cf9

Quelldatensatz

uspto-grants-2003_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06627629B2