1,1'-Carbonyldiimidazole → [4-(3-Pyridyloxymethyl)-2-phenylbenzoyl]methionine methylsulfonyl amide

Temperature

47.5 °C

A solution in THF (5 mL) of [4-(3-pyridyloxymethyl)-2-phenylbenzoyl]methionine (143 mg, 0.32 mmol), prepared as in Example 235, and carbonyldiimidazole (136 mg, 0.84 mmol) was stirred overnight at 45-50° C. A 1.6 mL aliquot of the reaction mixture was removed and to it was added methanesulfonamide (78 mg, 0.82 mmol) and DBU (0.12 mL, 0.80 mmol) and the mixture was stirred overnight at ambient temperature. The reaction mixture was partitioned between ethty acetate and pH 4 water. The organic phase was washed with water and brine, dried over sodium sulfate, filtered and concentrated in vacuo. Chromatographyl on silica gel (98.5:1.5:0.5 chloroform-methanol-acetic acid) gave [4-(3-pyridyloxymethyl)-2-phenylbenzoyl]methionine methylsulfonyl amide. (31 mg after azeotroping and lyophilization). 1H NMR (300 MHz, DMSO-d6) δ 8.62 (d, 1H), 8.39 (d, 1H), 8.18 (d, 1H), 7.50 (m, 4H), 7.36 (m, 6H), 5.28 (s, 2H), 4.27 (m, 1H), 3.21 (s, 3H), 2.20 (t, 2H), 2.02 (s, 3H), 1.81 (m, 2H). MS (APCI) m/e 514 (M+H)+. Anal calcd for C25H27N3O3S2.1.25H2O: C, 56.01; H, 5.55; N, 7.84. Found: C, 55.72; H, 5.08; N, 8.18.

1. customA 1.6 mL aliquot of the reaction mixture was removed and to it
2. stirringthe mixture was stirred overnight at ambient temperature
3. customThe reaction mixture was partitioned between ethty acetate and pH 4 water
4. washThe organic phase was washed with water and brine
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo

ORD record

ord-5268e53860934638930d08b230c161ac

Source dataset

uspto-grants-2004_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06693123B2