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

HRID 1930112Notes

Reaction equation

HRID 1930112 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]=[C:22]([CH3:24])[C:21]([CH2:25][C:26]([O:28]CC)=[O:27])=[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]=[C:22]([CH3:24])[C:21]([CH2:25][C:26]([OH:28])=[O:27])=[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 59627700Ethyl 2-(4'-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chloro-5-methylbiphenyl-4-yl)acetate2×

Product 1

HCID 498471742-(4'-(6-Carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chloro-5-methylbiphenyl-4-yl)acetic acidYield 90.6%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
55 °C

Procedure

Powdered potassium hydroxide (88 mg, 1.56 mmol) was added in one portion to ethyl 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chloro-5-methylbiphenyl-4-yl)acetate (Intermediate 3-1; 228 mg, 0.52 mmol) in tert-butanol (15 mL) at 55° C. The resulting mixture was stirred at 55° C. for 45 minutes, 2M HCl (˜1 mL) was added and the mixture was evaporated to remove the organic solvent. The suspension was collected by filtration, washed with water (20 mL) and air dried to afford crude product as a pale yellow solid, which contained a minor impurity. 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 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chloro-5-methylbiphenyl-4-yl)acetic acid (193 mg, 90%) as a cream solid.

Workup

  1. customthe mixture was evaporated
  2. customto remove the organic solvent
  3. filtrationThe suspension was collected by filtration
  4. washwashed with water (20 mL) and air
  5. customdried
  6. customto afford crude product as a pale yellow solid, which
  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-612e90f634fb4134a180780308803bcc
Source dataset
uspto-grants-2012_05
Patent number
US08188092B2

Reaction notes

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