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

HRID 2121217Notes

Reaction equation

HRID 2121217 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([O:7][CH2:8][C:9]2[CH:25]=[CH:24][C:12]([C:13]([NH:15][C@H:16]([C:21](O)=[O:22])[CH2:17][CH2:18][S:19][CH3:20])=[O:14])=[C:11]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH:10]=2)[CH:2]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH3:44][S:45]([NH2:48])(=[O:47])=[O:46].C1CCN2C(=NCCC2)CC1>C1COCC1>[CH3:44][S:45]([NH:48][C:21](=[O:22])[C@H:16]([CH2:17][CH2:18][S:19][CH3:20])[NH:15][C:13](=[O:14])[C:12]1[CH:24]=[CH:25][C:9]([CH2:8][O:7][C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)=[CH:10][C:11]=1[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)(=[O:47])=[O:46]

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 10694218[4-(3-Pyridyloxymethyl)-2-phenylbenzoyl]methionine

Product 1

HCID 59926679[4-(3-Pyridyloxymethyl)-2-phenylbenzoyl]methionine methylsulfonyl amide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
47.5 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-5268e53860934638930d08b230c161ac
Source dataset
uspto-grants-2004_02
Patent number
US06693123B2

Reaction notes

Loading…