Sodium Hydroxide → 4-(Isopropylamino)-2-(methylthio)pyrimidine-5-carboxylic Acid

HRID 2280775Notes

Reaction equation

HRID 2280775 reaction equation
[CH:1]([NH:4][C:5]1[C:10]([C:11]([O:13]CC)=[O:12])=[CH:9][N:8]=[C:7]([S:16][CH3:17])[N:6]=1)([CH3:3])[CH3:2].[OH-].[Na+]>C(O)C>[CH:1]([NH:4][C:5]1[C:10]([C:11]([OH:13])=[O:12])=[CH:9][N:8]=[C:7]([S:16][CH3:17])[N:6]=1)([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 10491237HCID 10491237, compound

Product 1

HCID 127840854-(Isopropylamino)-2-(methylthio)pyrimidine-5-carboxylic AcidYield 96.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Ethyl 4-(isopropylamino)-2-(methylthio)pyrimidine-5-carboxylate (1042 g, 4.08 mol, >100%, contaminated with trace DIEA) was dissolved in ethanol (10 L) and to the resulting solution was added a 2M aqueous sodium hydroxide solution (3.87 L, 7.74 mol). The resulting mixture was stirred overnight at ambient temperature and then concentrated under reduced pressure. The resulting residue was diluted with 2 L of water and then washed with methyl t-butyl ether (2×1.2 L). The pH of the aqueous layer was adjusted to pH 4.2-4.5 with a 2N aqueous hydrochloric acid solution. The resulting solids were collected by filtration, washed with water (2 L) and hexanes (2 L) and then dried overnight in a vacuum oven at 45° C. to afford 4-(isopropylamino)-2-(methylthio)pyrimidine-5-carboxylic acid (848 g, 96.5% yield over 2 steps) as an off-white solid. MS (ESI) m/z 228.1 [M+1]+.

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionThe resulting residue was diluted with 2 L of water
  3. washwashed with methyl t-butyl ether (2×1.2 L)
  4. filtrationThe resulting solids were collected by filtration
  5. washwashed with water (2 L) and hexanes (2 L)
  6. customdried overnight in a vacuum oven at 45° C.

Sources & evidence

ORD record
ord-b94fe382e06b47fcab86e5bd58bc2056
Source dataset
uspto-grants-2015_09
Patent number
US09139534B2

Reaction notes

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