反应详情

温度

80 °C

In a 20 mL vial, [5-(4-bromo-phenyl)-3-methyl-3H-[1,2,3]triazol-4-yl]-carbamic acid (R)-1-(3-trifluoromethyl-phenyl)-ethyl ester (123.7 mg, 264 μmol), N-{1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarbonyl}-methanesulfonamide (110 mg, 301 μmol), DPPF (36 mg, 64.9 μmol) and PdCl2(dppOCH2Cl2 (40 mg, 49.0 μmol) were combined with DMF (5 mL, with nitrogen bubbled through for 20 min) to give a light brown/red solution. To this was added 2N Na2CO3 (527 μl, 1.05 mmol, with nitrogen bubbled through for 20 min), the red mixture (looked like salt precipitated) had nitrogen bubbled through for 1 min. The vial was sealed, placed in a dry block, and heated at 80° C. for 4 hr. The reaction was diluted with ethyl acetate (75 mL) and 0.1 M HCl (100 mL). The layers were separated. The aqueous layer was extracted with ethyl acetate (75 mL). The organic layers were washed with brine, dried over MgSO4, filtered, concentrated, and dried from DCM/hexanes to give a crude material (311 mg). The crude material was dissolved in minimal DCM and purified by flash chromatography (silica gel, 24 g Redisep, 30 mL/min, 0% to 100% EtOAc in hexanes, 0.5% AcOH). Appropriate fractions were combined, concentrated, dried from DCM/hexanes to yield {5-[4′-(1-methane-sulfonylamino carbonyl-cyclopropyl)-biphenyl-4-yl]-3-methyl-3H-[1,2,3]triazol-4-yl}-carbamic acid (R)-1-(3-trifluoromethyl-phenyl)-ethyl ester (69.2 mg, 41.8% yield) as a brown solid. C30H28F3N5O5S (m/e) 627, obsd. 628 (M+H, ES+). 1H NMR (DMSO-d6) δ ppm 11.16 (br. s., 1H), 9.47-10.15 (m, 1H), 7.53-7.94 (m, 10H), 7.41 (d, J=8.3 Hz, 2H), 5.89 (br. s., 1H), 3.86 (br. s., 3H), 3.20 (s, 3H), 1.60 (br. s., 3H), 1.47-1.53 (m, 2H), 1.20 (d, J=1.8 Hz, 2H).

1. customto give a light brown/red solution
2. customthe red mixture (looked like salt precipitated)
3. custombubbled through for 1 min
4. customThe vial was sealed
5. additionThe reaction was diluted with ethyl acetate (75 mL) and 0.1 M HCl (100 mL)
6. customThe layers were separated
7. extractionThe aqueous layer was extracted with ethyl acetate (75 mL)
8. washThe organic layers were washed with brine
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated
12. dry with materialdried from DCM/hexanes
13. customto give a crude material (311 mg)
14. custompurified by flash chromatography (silica gel, 24 g Redisep, 30 mL/min, 0% to 100% EtOAc in hexanes, 0.5% AcOH)
15. concentrationconcentrated
16. dry with materialdried from DCM/hexanes