Potassium Carbonate → {[2-[(3,5-Dimethoxy-4-methyl-benzoylamino)-methyl]-5-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-phenethyl-amino}-acetic acid

HRID 1296753Notes

Reaction equation

HRID 1296753 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:31]=[C:32]([O:35][CH3:36])[C:33]=1[CH3:34])[C:6]([NH:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[N:20]=[C:19]([CH3:21])[O:18][N:17]=2)=[CH:12][C:11]=1[NH:22][CH2:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:7].Br[CH2:38][C:39]([O:41]C)=[O:40].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:31]=[C:32]([O:35][CH3:36])[C:33]=1[CH3:34])[C:6]([NH:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[N:20]=[C:19]([CH3:21])[O:18][N:17]=2)=[CH:12][C:11]=1[N:22]([CH2:38][C:39]([OH:41])=[O:40])[CH2:23][CH2:24][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)=[O:7]

Participants

5

Reactant 3

HCID 11430Potassium Carbonate2×HCID 60984Methyl bromoacetate2×HCID 694916163,5-Dimethoxy-4-methyl-N-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)-2-phenethylamino-benzyl]-benzamide

Product 1

HCID 69491530{[2-[(3,5-Dimethoxy-4-methyl-benzoylamino)-methyl]-5-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-phenethyl-amino}-acetic acidYield 62%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A solution of compound 9a (45 mg, 0.092 mmol), methyl bromoacetate (0.053 mL, 0.56 mmol), and potassium carbonate (38 mg, 0.27 mmol) in DMF (1 mL) was sealed in a pressure tube and heated at 80° C. overnight and at rt for two days. Additional methyl bromoacetate (0.060 mL) and potassium carbonate (42 mg) was added and the reaction was heated at 100° C. for 5 h. The reaction mixture was filtered and concentrated on a rotary evaporator. The residue was purified by preparative tlc. This compound was dissolved in a mixture of THF (1 mL) containing several drops of MeOH and 10% LiOH (1 mL). The reaction mixture was stirred at rt for 4 h, neutralized, and concentrated on a rotary evaporator. The residue was dissolved in ethyl acetate, washed with water, dried, and concentrated to give compound 22a (31 mg, 62%). ESI-MS m/e 545.4 (M+1).

Workup

  1. temperaturethe reaction was heated at 100° C. for 5 h
  2. filtrationThe reaction mixture was filtered
  3. concentrationconcentrated on a rotary evaporator
  4. customThe residue was purified by preparative tlc
  5. dissolutionThis compound was dissolved in a mixture of THF (1 mL)
  6. additioncontaining several drops of MeOH and 10% LiOH (1 mL)
  7. concentrationneutralized, and concentrated on a rotary evaporator
  8. dissolutionThe residue was dissolved in ethyl acetate
  9. washwashed with water
  10. customdried
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-1146540f63f94e36ab249dc1b94f69d8
Source dataset
uspto-grants-2007_07
Patent number
US07247654B2

Reaction notes

Loading…