Lithium Hydroxide → 6-[Cyclohexyl(methyl)amino]pyrimidine-4-carboxylic acid

HRID 1946666Notes

Reaction equation

HRID 1946666 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([O:10]C)=[O:9])[CH:5]=[C:4]([N:12]([CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)[CH3:13])[N:3]=1.C(N(CC)CC)C.C1(N(C)C2N=CN=C(C(OC)=O)C=2)CCCCC1.C1(N(C)C2N=CN=C(C(OCC)=O)C=2)CCCCC1.[OH-].[Li+]>[Pd].CCO.C1COCC1.CCO.O>[CH:14]1([N:12]([CH3:13])[C:4]2[N:3]=[CH:2][N:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=2)[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]1

Participants

9

Reactant 5

HCID 3939Lithium HydroxideHCID 8471TriethylamineHCID 59446979HCID 59446979, compound2×HCID 68487764HCID 68487764, compoundHCID 68488270HCID 68488270, compound

Product 1

HCID 594470776-[Cyclohexyl(methyl)amino]pyrimidine-4-carboxylic acid

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 18504229Ethanol tetrahydrofuran waterSolvent

Procedure

A mixture of methyl 2-chloro-6-[cyclohexyl(methyl)amino]pyrimidine-4-carboxylate (Intermediate 9, 10.00 g; 35.2 mmol), triethylamine (14.7 mL; 105 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-[cyclohexyl(methyl)amino]pyrimidine-4-carboxylate and ethyl 6-[cyclohexyl(methyl)amino]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, 105 mL, 105 mmol). After 1 hour, the organic solvents were evaporated in vacuo and water (900) was added. The aqueous layer was washed with DCM (200 mL), then acidified to pH 4 by addition of a HCl solution (1N). The aqueous layer was evaporated to reduce the volume by 30-50%. A precipitate 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 (900)
  6. additionwas added
  7. washThe aqueous layer was washed with DCM (200 mL)
  8. additionacidified to pH 4 by addition of a HCl solution (1N)
  9. customThe aqueous layer was evaporated
  10. filtrationwas filtered

Sources & evidence

ORD record
ord-82e0a1d6549749f398bb551de41236a9
Source dataset
uspto-grants-2013_03
Patent number
US08399448B2

Reaction notes

Loading…