Potassium Hydroxide → HCID 49846147, compound

HRID 1930153Notes

Reaction equation

HRID 1930153 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][C@@H:28]([CH:33]([CH3:35])[CH3:34])[C:29]([O:31]C)=[O:30])=[O:26])=[CH:20][C:19]=3[Cl:36])=[CH:14][CH:13]=2)[C:9]([CH3:37])=[N:8][C:7]=1[CH3:38])(=[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][C@@H:28]([CH:33]([CH3:34])[CH3:35])[C:29]([OH:31])=[O:30])=[O:26])=[CH:20][C:19]=3[Cl:36])=[CH:14][CH:13]=2)[C:9]([CH3:37])=[N:8][C:7]=1[CH3:38])(=[O:5])[NH2:4]

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 59627652HCID 59627652, compound2×

Product 1

HCID 49846147HCID 49846147, compoundYield 29.4%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
45 °C

Procedure

Potassium hydroxide (108 mg, 1.93 mmol) was added in one portion to (S)-methyl 2-(2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetamido)-3-methylbutanoate (Intermediate 17-1; 327.4 mg, 0.64 mmol) in t-BuOH (4150 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 (S)-2-(2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetamido)-3-methylbutanoic acid (93 mg, 29.1%) 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-78e42623733e437fb2548082e1929cf5
Source dataset
uspto-grants-2012_05
Patent number
US08188092B2

Reaction notes

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