Application of 147356-78-3, These common heterocyclic compound, 147356-78-3, name is N-Methoxy-N-methylcyclopropanecarboxamide, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
Isopropylmagnesium chloride (2.0 M in THF, 2.4 mL, 4.76 mmol) was added dropwise to a solution of a 2:1 mixture of (5S,7R)-2-bromo-5-(o-tolyl)-6,7-dihydro-5H-pyrrolo[l,2-b][l,2,4]triazol-7-ol and (5S,7R)-2-bromo-7-fluoro-5-(o-tolyl)-6,7-dihydro-5H-pyrrolo[l,2-b][l,2,4]triazole (0.470 g) and N- methoxy-N-methylcyclopropanecarboxamide (0.634 g, 4.76 mmol) in THF (15.9 mL) at 0C over 15 min. After lh, saturated aqueous ammonium chloride was added. The aqueous layer was extracted with isopropyl acetate (2 x 20 mL). The combined organic layers were dried over sodium sulfate, concentrated and the crude residue was purified by prep HPLC/SFC to afford arbitrarily assigned cyclopropyl((5S,7R)-7-fluoro-5-(o olyl)-6,7-dihydro-5H-pyrrolo[l,2-b][l ,2,4]triazol-2-yl)methanone (137 mg, 0.480 mmol) and cyclopropyl((5S,7R)-7-hydroxy-5-(o-tolyl)-6,7-dihydro-5H-pyrrolo[l,2- b][l,2,4]triazol-2-yl)methanone (33.8 mg, 0.119 mmol). cyclopropyl((5S,7R)-7-fluoro-5-(o-tolyl)-6,7-dihydro-5H-pyrrolo[l,2-b][l ,2,4]triazol-2- yl)methanone: NMR (400 MHz, DMSO-i) delta 7.33 – 7.14 (m, 3H), 6.89 (d, J= 7.5 Hz, 1H), 6.35 (ddd, J = 56.2, 6.8, 1.6 Hz, 1H), 6.19 (td, J = 6.9, 3.2 Hz, 1H), 3.59 – 3.27 (m, 1H), 3.11 – 2.91 (m, 2H), 2.38 (s, 3H), 1.14 – 1.01 (m, 4H). LCMS RT = 4.81 min, m/z = 286.1 [M + H]+. Prep SFC Information: Column: Torus Diol 5 muiotaeta, (150 x 30 mm), Mobile Phase: Carbon Dioxide (A) / 0.1 % Ammonium Hydroxide in Methanol (B), Elution Program Isocratic: 5% B Flow Rate: 150 mL/min, Column Temperature: 25 C, Wavelength: 220 nm cyclopropyl((5S,7R)-7-hydroxy-5-(o-tolyl)-6,7-dihydro-5H-pyrrolo[l,2-b][l,2,4]triazol-2- yl)methanone: NMR (400 MHz, DMSO-d6) delta 7.30 – 7.13 (m, 3H), 7.01 – 6.94 (m, 1H), 6.25 (bs, 1H), 5.75 (dd, J = 8.1, 5.8 Hz, 1H), 5.23 (dd, J = 7.9, 4.6 Hz, 1H), 3.63 – 3.52 (m, 1H), 3.03 – 2.92 (m, 1H), 2.38 (s, 3H), 2.31 – 2.14 (m, 1H), 1.09 – 0.96 (m, 4H). LCMS RT = 4.08 min, m/z = 284.1 [M + H]+. Prep HPLC Information: Column: Gemini-NX CI 8, 5muiotaeta (50 x 30 mm), Mobile Phase: 0.1 % Ammonium Hydroxide in Water (A) / Acetonitrile (B), Elution Program Gradient: 10% to 60%> B Flow Rate: 60 mL/min, Column Temperature: 25 C, Wavelength: 254 nm
The synthetic route of 147356-78-3 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; F. HOFFMANN-LA ROCHE AG; GENENTECH, INC.; PATEL, Snahel; HAMILTON, Gregory; ZHAO, Guiling; CHEN, Huifen; DANIELS, Blake; STIVALA, Craig; (358 pag.)WO2019/12063; (2019); A1;,
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