Triethylamine → (R)-N-(2,2-Dimethoxyethyl)-3-(3-(1-methyl-1H-pyrazol-4-yl)phenethoxy)-N-(3-methylbutan-2-yl)propanamide

Temperatur

25 °C

A solution of T3P (1.86 mL) dissolved in THF (1.57M) was added in one portion to a stirred solution of 3-(3-(1-methyl-1H-pyrazol-4-yl)phenethoxy)propanoic acid [Example 2a, Step i)] (567 mg), (R)—N-(2,2-dimethoxyethyl)-3-methylbutan-2-amine [Preparation 4] (307 mg), and triethylamine (2.44 mL) in acetonitrile (6 mL) at 25° C. The resulting solution was stirred at 25° C. for 15 min. The reaction mixture was diluted with ethyl acetate (50 mL), and washed with saturated sodium hydrogen carbonate (20 mL). The organic layer was dried over magnesium sulfate, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0-100% ethyl acetate in isohexane, then elution gradient 5-10% methanol in ethyl acetate to afford the subtitled compound as a gum (210 mg). 1H NMR (400 MHz, CD3OD) δ 7.92 and 7.91 (2×s, 1H), 7.77 (s, 1H), 7.40-7.37 (m, 1H), 7.36-7.32 (m, 1H), 7.23 and 7.22 (2×t, J=7.7 Hz, 1H), 7.05 (d, J=7.6 Hz, 1H), 4.59 and 4.43 (2×t, J=5.4 Hz, 1H), 3.90 (s, 3H), 3.75-3.45 (m, 5H), 3.36 (d, J=1.5 Hz, 2H), 3.35, 3.34, 3.33, 3.32 (4×s, 6H), 2.84 and 2.84 (2×t, J=7.0 Hz, 2H), 2.76-2.61 (m, 2H), 1.98-1.86 and 1.79-1.66 (2×m, 1H), 1.16 and 1.14 (2×d, J=7.0 Hz, 3H), 0.90 and 0.88 (2×d, J=6.8 Hz, 3H), 0.79 and 0.75 (2×d, J=6.8 Hz, 3H), a ˜1:1 mixture of rotamers is observed.

1. washwashed with saturated sodium hydrogen carbonate (20 mL)
2. dry with materialThe organic layer was dried over magnesium sulfate
3. filtrationfiltered
4. customevaporated
5. customto afford crude product
6. customThe crude product was purified by flash silica chromatography, elution gradient 0-100% ethyl acetate in isohexane
7. washelution gradient 5-10% methanol in ethyl acetate

ORD-Eintrag

ord-2a68b9b72bb94af0b95512feabbe503e

Quelldatensatz

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08017602B2