Hydrochloric Acid → 1-(4'-(6-Carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)cyclopropanecarboxylic acid

HRID 1930140Notes

Reaction equation

HRID 1930140 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]([C:24]4([C:27]([O:29]C)=[O:28])[CH2:26][CH2:25]4)=[CH:20][C:19]=3[Cl:31])=[CH:14][CH:13]=2)[C:9]([CH3:32])=[N:8][C:7]=1[CH3:33])(=[O:5])[NH2:4].Cl>C(O)(C)(C)C>[C:3]([C:6]1[N:11]=[C:10]([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4([C:27]([OH:29])=[O:28])[CH2:25][CH2:26]4)=[CH:20][C:19]=3[Cl:31])=[CH:16][CH:17]=2)[C:9]([CH3:32])=[N:8][C:7]=1[CH3:33])(=[O:5])[NH2:4]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 59627667Methyl 1-(4'-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)cyclopropanecarboxylate2×

Product 1

HCID 498461431-(4'-(6-Carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)cyclopropanecarboxylic acidYield 22.96%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
45 °C

Procedure

Powdered potassium hydroxide (52.1 mg, 0.93 mmol) was added in one portion to methyl 1-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)cyclopropanecarboxylate (Intermediate 10-1; 135 mg, 0.31 mmol) in tert-butanol (5 mL) at 45° C. The resulting solution was stirred at 45° C. for 30 minutes. 2N HCl (1 mL) was added and the mixture was evaporated to remove the organic solvent. The suspension was collected by filtration, washed with water and dried under vacuum to afford crude product. 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% TFA) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 1-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)cyclopropanecarboxylic acid (30.0 mg, 22.96%) as a white solid.

Workup

  1. customthe mixture was evaporated
  2. customto remove the organic solvent
  3. filtrationThe suspension was collected by filtration
  4. washwashed with water
  5. customdried under vacuum
  6. customto afford crude product
  7. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length)
  8. additionFractions containing the desired compound
  9. customwere evaporated to dryness

Sources & evidence

ORD record
ord-a4dfce23b0654f29a978f9afeb86d735
Source dataset
uspto-grants-2012_05
Patent number
US08188092B2

Reaction notes

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