Potassium Hydroxide → 3-(2-(4'-(6-Carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetamido)propanoic acid

HRID 1930151Notes

Reaction equation

HRID 1930151 reaction equation
[OH-].[K+].[C:3]([C:6]1[N:11]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][C:21]([CH2:24][C:25]([NH:27][CH2:28][CH2:29][C:30]([O:32]CC)=[O:31])=[O:26])=[CH:20][C:19]=3[Cl:35])=[CH:14][CH:13]=2)[C:9]([CH3:36])=[N:8][C:7]=1[CH3:37])(=[O:5])[NH2:4]>CC(O)(C)C>[C:3]([C:6]1[N:11]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][C:21]([CH2:24][C:25]([NH:27][CH2:28][CH2:29][C:30]([OH:32])=[O:31])=[O:26])=[CH:20][C:19]=3[Cl:35])=[CH:14][CH:13]=2)[C:9]([CH3:36])=[N:8][C:7]=1[CH3:37])(=[O:5])[NH2:4]

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 59627636Ethyl 3-(2-(4'-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetamido)propanoate2×

Product 1

HCID 672857433-(2-(4'-(6-Carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetamido)propanoic acidYield 15.5%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
45 °C

Procedure

Potassium hydroxide (131 mg, 2.34 mmol) was added in one portion to ethyl 3-(2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetamido)propanoate (Intermediate 16-1; 386.5 mg, 0.78 mmol) in t-BuOH (5038 μL) at RT. The resulting solution was stirred at 45° C. for 5 hours a precipitate formed. The reaction mixture was quenched with 2M HCl (5 mL), The reaction mixture was evaporated to dryness and redissolved in water (10 mL), and filtered through nylon, washed with water and dried under vacuum. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 0.1% formic acid) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 3-(2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetamido)propanoic acid (56.4 mg, 15.47%) as a white solid.

Workup

  1. customformed
  2. customThe reaction mixture was quenched with 2M HCl (5 mL)
  3. customThe reaction mixture was evaporated to dryness
  4. dissolutionredissolved in water (10 mL)
  5. filtrationfiltered through nylon
  6. washwashed with water
  7. customdried under vacuum
  8. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length)
  9. additionFractions containing the desired compound
  10. customwere evaporated to dryness

Sources & evidence

ORD record
ord-e92d327c4e244c67984f2c43e255911d
Source dataset
uspto-grants-2012_05
Patent number
US08188092B2

Reaction notes

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