Triethylamine → Methyl 2-chloro-6-[cyclohexyl(cyclopropylmethyl)amino]pyrimidine-4-carboxylate

HRID 1946667Notes

Reaction equation

HRID 1946667 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[N:3]=1.C(N(CC)CC)C.Cl.[CH:21]1([NH:27][CH2:28][CH:29]2[CH2:31][CH2:30]2)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1>C1COCC1>[Cl:1][C:2]1[N:3]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[CH:5]=[C:6]([N:27]([CH:21]2[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]2)[CH2:28][CH:29]2[CH2:31][CH2:30]2)[N:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 239689Methyl 2,4-dichloropyrimidine-6-carboxylateHCID 16641250N-(Cyclopropylmethyl)cyclohexanamine hydrochloride

Product 1

HCID 59446993Methyl 2-chloro-6-[cyclohexyl(cyclopropylmethyl)amino]pyrimidine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A cooled (0° C.) solution of methyl 2,4-dichloropyrimidine-6-carboxylate (Apollo, OR2558, 5.00 g; 24.1 mmol) in THF (50 mL) was treated triethylamine (7.38 ml; 53.1 mmol) and cyclohexyl(cyclopropylmethyl)amine hydrochloride (Chembridge, 4.58 g; 24.1 mmol. The reaction mixture was stirred for 2 days at RT. The solvent was evaporated under reduced pressure, the remaining residue was partitioned between 100 ml of ethyl acetate and a saturated aqueous solution of NH4Cl (50 mL). The organic phase was washed with brine, dried over magnesium sulfate, filtered and concentrated to obtain the crude product, which was purified by column chromatography (silica) eluting with cyclohexane containing increasing amounts of EtOAc to give the title product as a yellow oil, which solidified upon standing (6.14 g, 78%).

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. customthe remaining residue was partitioned between 100 ml of ethyl acetate
  3. washThe organic phase was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto obtain the crude product, which
  8. customwas purified by column chromatography (silica)
  9. washeluting with cyclohexane containing
  10. temperatureincreasing amounts of EtOAc

Sources & evidence

ORD record
ord-33eda11970ee4e9a99c0dbea1159cd53
Source dataset
uspto-grants-2013_03
Patent number
US08399448B2

Reaction notes

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