반응 #685021

반응 방정식

solution

Benzyl 2-(4-fluoro-2-(5-methyl-1H-1,2,4-triazol-1-yl)benzylcarbamoyl)-3-hydroxy-4-oxo-6,7-dihydro-4H-spiro[pyrimido[2,1-c][1,4]oxazine-9,3′-pyrrolidine]-1′-carboxylate

HBr

HBr AcOH

→

desired product

수율 51.1%

N-(4-Fluoro-2-(5-methyl-1H-1,2,4-triazol-1-yl)benzyl)-3-hydroxy-4-oxo-6,7-dihydro-4H-spiro[pyrimido[2,1-c][1,4]oxazine-9,3′-pyrrolidine]-2-carboxamide

수율 51.1%

용매

1,4-dioxane

AcOH

반응 조건

후처리

1. 1
   기타to the reaction, solids
2. 2
   기타precipitated out of the reaction mixture
3. 3
   workup.ADDITIONSo, 3 mL of anhydrous MeOH was added
4. 4
   기타Then, the reaction mixture was purified by preparative HPLC

실험 절차

To a stirred solution of Example 37 (1.1358 g, 1.9265 mmol) in 1,4-dioxane (10 mL) was added 33 wt % HBr in AcOH (2 mL) at room temperature. Immediately upon addition of HBr/AcOH to the reaction, solids precipitated out of the reaction mixture. So, 3 mL of anhydrous MeOH was added and stirred for 2 h. Then, the reaction mixture was purified by preparative HPLC using water/MeOH containing 0.1% TFA to afford desired product (0.448 g, 41%) as white solid. 1H NMR (500 MHz, DMSO-d6) δ: 1205 (1H, s), 9.35-9.28 (1H, br s), 9.27-9.19 (1H, br s), 9.14 (1H, t, J=6.1 Hz), 8.12 (1H, s), 7.57-7.53 (2H, m), 7.48-7.44 (1H, m), 4.27 (2H, d, J=6.1 Hz), 4.09-4.05 (2H, m), 3.91-3.86 (2H, m), 3.70-3.49 (3H, m), 3.42-3.34 (1H, m), 2.66-2.59 (1H, m), 2.45-2.39 (1H, m), 2.33 (3H, s). HRMS (M+H) calcd for C21H23N7O4F: 456.1796; found: 456.1805.

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