Hydrochloric Acid → [4-({1-[1-(tert-Butoxycarbonyl)-4-(cyanomethyl)piperidin-4-yl]-4-carbamoyl-1H-pyrazol-3-yl}amino)phenyl]acetic acid

HRID 521224Notes

Reaction equation

HRID 521224 reaction equation
[C:1]([C:4]1[C:5]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([CH2:32][C:33]([O:35]C)=[O:34])=[CH:28][CH:27]=2)=[N:6][N:7]([C:9]2([CH2:22][C:23]#[N:24])[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)[CH:8]=1)(=[O:3])[NH2:2].[Li+].[OH-].Cl>C1COCC1.O>[C:18]([O:17][C:15]([N:12]1[CH2:13][CH2:14][C:9]([N:7]2[CH:8]=[C:4]([C:1](=[O:3])[NH2:2])[C:5]([NH:25][C:26]3[CH:27]=[CH:28][C:29]([CH2:32][C:33]([OH:35])=[O:34])=[CH:30][CH:31]=3)=[N:6]2)([CH2:22][C:23]#[N:24])[CH2:10][CH2:11]1)=[O:16])([CH3:21])([CH3:19])[CH3:20]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 86729389tert-butyl 4-(4-carbamoyl-3-{[4-(2-methoxy-2-oxoethyl)phenyl]amino}-1H-pyrazol-1-yl)-4-(cyanomethyl)piperidine-1-carboxylate

Product 1

HCID 86729388[4-({1-[1-(tert-Butoxycarbonyl)-4-(cyanomethyl)piperidin-4-yl]-4-carbamoyl-1H-pyrazol-3-yl}amino)phenyl]acetic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl 4-(4-carbamoyl-3-{[4-(2-methoxy-2-oxoethyl)phenyl]amino}-1H-pyrazol-1-yl)-4-(cyanomethyl)piperidine-1-carboxylate (Example 12-2) (0.10 g, 0.20 mmol) in THF (1.0 mL) was added a solution of LiOH (19 mg, 0.81 mmol) in water (0.8 mL). The mixture was stirred at ambient temperature for 2 hours. The mixture was then neutralized with 1N aqueous HCl to pH 3-4, diluted with water, and extracted with EtOAc. The organic layer was separated, washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The residue was purified by MPLC on silica gel (using a gradient elution of 0-10% MeOH/EtOAc) to afford the title compound, Example #18.

Workup

  1. extractionextracted with EtOAc
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over anhydrous MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by MPLC on silica gel (
  7. washa gradient elution of 0-10% MeOH/EtOAc)

Sources & evidence

ORD record
ord-0c6b12df601948178762a5ac3677564b
Source dataset
uspto-grants-2016_05
Patent number
US09328099B2

Reaction notes

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