Lithium Hydroxide → 6-(Cyclohexylamino)pyrimidine-4-carboxylic acid

HRID 1746645Notes

Reaction equation

HRID 1746645 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([O:10]C)=[O:9])[CH:5]=[C:4]([NH:12][CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)[N:3]=1.C(N(CC)CC)C.C1(NC2N=CN=C(C(OC)=O)C=2)CCCCC1.C1(NC2N=CN=C(C(OCC)=O)C=2)CCCCC1.[OH-].[Li+]>[Pd].CCO.C1COCC1.CCO.O>[CH:13]1([NH:12][C:4]2[N:3]=[CH:2][N:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=2)[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]1

Participants

9

Reactant 5

HCID 3939Lithium HydroxideHCID 8471TriethylamineHCID 59447049Methyl 2-chloro-6-(cyclohexylamino)pyrimidine-4-carboxylate2×HCID 68487155HCID 68487155, compoundHCID 68488572Ethyl 6-(cyclohexylamino)pyrimidine-4-carboxylate

Product 1

HCID 594470756-(Cyclohexylamino)pyrimidine-4-carboxylic acid

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 18504229Ethanol tetrahydrofuran waterSolvent

Procedure

A mixture of methyl 2-chloro-6-(cyclohexylamino)pyrimidine-4-carboxylate (Intermediate 1, 9.20 g; 34.1 mmol), triethylamine (14.3 mL; 102 mmol) and palladium on charcoal (750 mg) in EtOH (1 L) was stirred at RT under an atmosphere of hydrogen for 16 hours. The reaction mixture was filtered through celite and the solvent was evaporated in vacuo to give a mixture of methyl 6-(cyclohexylamino)pyrimidine-4-carboxylate and ethyl 6-(cyclohexylamino)pyrimidine-4-carboxylate. This crude was dissolved in a mixture of THF/EtOH/H2O (3/2/1, 1 L) and treated with an aqueous lithium hydroxide solution (1N, 102 mmol). After 1 hour, the organic solvents were evaporated in vacuo and water was added. The aqueous layer was washed with DCM (200 mL), then acidified to pH 4 by addition of an HCl solution (1N). The aqueous layer was evaporated to reduce the volume by 30-50%. A white solid appeared and was filtered to afford the title compound as a white solid.

Workup

  1. filtrationThe reaction mixture was filtered through celite
  2. customthe solvent was evaporated in vacuo
  3. customto give
  4. waitAfter 1 hour
  5. customthe organic solvents were evaporated in vacuo and water
  6. additionwas added
  7. washThe aqueous layer was washed with DCM (200 mL)
  8. additionacidified to pH 4 by addition of an HCl solution (1N)
  9. customThe aqueous layer was evaporated
  10. filtrationwas filtered

Sources & evidence

ORD record
ord-3de2f7f956434e5ab390f152f29a9d8e
Source dataset
uspto-grants-2015_10
Patent number
US09150519B2

Reaction notes

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