Hydrochloric Acid → 2-(2-(4'-(6-Carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetamido)acetic acid

HRID 1930158Notes

Reaction equation

HRID 1930158 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][C:29]([O:31]C)=[O:30])=[O:26])=[CH:20][C:19]=3[Cl:33])=[CH:14][CH:13]=2)[C:9]([CH3:34])=[N:8][C:7]=1[CH3:35])(=[O:5])[NH2:4].Cl>C(O)(C)(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][C:29]([OH:31])=[O:30])=[O:26])=[CH:20][C:19]=3[Cl:33])=[CH:14][CH:13]=2)[C:9]([CH3:34])=[N:8][C:7]=1[CH3:35])(=[O:5])[NH2:4]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 67285289Methyl 2-(2-(4'-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetamido)acetate2×

Product 1

HCID 672857212-(2-(4'-(6-Carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetamido)acetic acidYield 19.92%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
45 °C

Procedure

Powdered potassium hydroxide (106 mg, 1.89 mmol) was added in one portion to methyl 2-(2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetamido)acetate (Intermediate 20-1; 294 mg, 0.63 mmol) in tert-butanol (4062 μL) at 45° C. The resulting solution was stirred at 45° C. for 150 minutes, a thick white suspension slowly precipitate formed. 2M HCl (5 mL) was added and the mixture was evaporated to remove the organic solvent. The reaction mixture was diluted with EtOAc and water, the organic layer was collected, dried with MgSO4 and evaporated to afford crude product. This 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 2-(2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetamido)acetic acid (56.8 mg, 19.92%) as a white solid.

Workup

  1. customa thick white suspension slowly precipitate
  2. customformed
  3. customthe mixture was evaporated
  4. customto remove the organic solvent
  5. additionThe reaction mixture was diluted with EtOAc and water
  6. customthe organic layer was collected
  7. dry with materialdried with MgSO4
  8. customevaporated
  9. customto afford crude product
  10. customThis was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length)
  11. additionFractions containing the desired compound
  12. customwere evaporated to dryness

Sources & evidence

ORD record
ord-f5d0c32caff2459ebbad17fbc42b80fe
Source dataset
uspto-grants-2012_05
Patent number
US08188092B2

Reaction notes

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