Potassium Hydroxide → HCID 49846224, compound

HRID 1930156Notes

Reaction equation

HRID 1930156 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]([N:27]4[CH2:32][CH2:31][CH:30]([C:33]([O:35]CC)=[O:34])[CH2:29][CH2:28]4)=[O:26])=[CH:20][C:19]=3[Cl:38])=[CH:14][CH:13]=2)[C:9]([CH3:39])=[N:8][C:7]=1[CH3:40])(=[O:5])[NH2:4]>CC(O)(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]([CH2:24][C:25]([N:27]4[CH2:28][CH2:29][CH:30]([C:33]([OH:35])=[O:34])[CH2:31][CH2:32]4)=[O:26])=[CH:20][C:19]=3[Cl:38])=[CH:16][CH:17]=2)[C:9]([CH3:39])=[N:8][C:7]=1[CH3:40])(=[O:5])[NH2:4]

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 59627658HCID 59627658, compound2×

Product 1

HCID 49846224HCID 49846224, compoundYield 21.8%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
45 °C

Procedure

Potassium hydroxide (91 mg, 1.63 mmol) was added in one portion to ethyl 1-(2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetyl)piperidine-4-carboxylate (Intermediate 19-1; 290.7 mg, 0.54 mmol) in t-BuOH (3505 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 1-(2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetyl)piperidine-4-carboxylic acid (59.8 mg, 21.71%) 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-8030357754c745109c9eebef432f4c60
Source dataset
uspto-grants-2012_05
Patent number
US08188092B2

Reaction notes

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