Lithium hydroxide, monohydrate → 4-(2-amino-5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-2-methylbenzoic acid

HRID 596083Notes

Reaction equation

HRID 596083 reaction equation
[NH2:1][C:2]1[C:7]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14]C)=[O:13])=[C:10]([CH3:18])[CH:9]=2)=[CH:6][C:5]([C:19]2[CH:20]=[N:21][N:22]([CH3:24])[CH:23]=2)=[CH:4][N:3]=1.O[Li].O>C1COCC1.CO.O>[NH2:1][C:2]1[C:7]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([OH:14])=[O:13])=[C:10]([CH3:18])[CH:9]=2)=[CH:6][C:5]([C:19]2[CH:20]=[N:21][N:22]([CH3:24])[CH:23]=2)=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 118045392methyl 4-(2-amino-5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-2-methylbenzoate

Product 1

HCID 1180462104-(2-amino-5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-2-methylbenzoic acidYield 69.7%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

To a solution of methyl 4-(2-amino-5-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-2-methylbenzoate (1.20 g, 3.72 mmol) in THF/MeOH/H2O (1:1:1, 36 mL) was added LiOH—H2O (0.234 g, 5.58 mmol). The solution was stirred at room temperature overnight. The pH was adjusted to 3-5, optimally 4. All the organic solvents were removed by reduced pressure. EtOAc was added to triturate out all the impurities. Water was added and the mixture was stirred for 30 min. Solid was filtered and washed well with 50% of ether and water. The solid was then azotropied on rotovap with toluene to provide about 800 mg of desired acid in 69.7% yield. LCMS (m/z): 309.2 (MH+), 0.50 min.

Workup

  1. customAll the organic solvents were removed by reduced pressure
  2. additionEtOAc was added
  3. customto triturate out all the impurities
  4. additionWater was added
  5. stirringthe mixture was stirred for 30 min
  6. filtrationSolid was filtered
  7. washwashed well with 50% of ether and water

Sources & evidence

ORD record
ord-8cb2b066fbef45379faf8a67275e9ca8
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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