Ethyl Acetate → (1,1-dimethylethyl) 3-[[6-[4-(methoxycarbonyl)-1-piperidinyl]-5-methyl-4-pyrimidinyl]amino]-N-[(phenylmethoxy)carbonyl]alaninate

HRID 729743Notes

Reaction equation

HRID 729743 reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][CH2:9][C@@H:10]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[NH:11][C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[C:3]=1[CH3:29].[NH:30]1[CH2:35][CH2:34][CH:33]([C:36]([O:38][CH3:39])=[O:37])[CH2:32][CH2:31]1.C(OCC)(=O)C.C(=O)(O)[O-].[Na+]>O>[CH3:39][O:38][C:36]([CH:33]1[CH2:34][CH2:35][N:30]([C:2]2[N:7]=[CH:6][N:5]=[C:4]([NH:8][CH2:9][C@@H:10]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[NH:11][C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[O:13])[C:3]=2[CH3:29])[CH2:31][CH2:32]1)=[O:37]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 424914Methyl isonipecotateHCID 516892Sodium BicarbonateHCID 12094347(1,1-Dimethylethyl)-3-[(6-chloro-5-methyl-4-pyrimidinyl)amino]-n-[(phenylmethoxy)carbonyl]alaninate

Product 1

HCID 12094348(1,1-dimethylethyl) 3-[[6-[4-(methoxycarbonyl)-1-piperidinyl]-5-methyl-4-pyrimidinyl]amino]-N-[(phenylmethoxy)carbonyl]alaninateYield 25%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 80 mg (0.19 mmoles) of (1,1-dimethylethyl) 3-[(6-chloro-5-methyl-4-pyrimidinyl)amino]-N-[(phenylmethoxy) carbonyl]alaninate and 3 ml of methyl 4-piperidinylcarboxylate is heated under reflux for 3 hours. After cooling down the reaction medium is taken up in water, ethyl acetate and a saturated solution of sodium bicarbonate. The organic phase is separated and the aqueous phase reextracted with ethyl acetate. The combined organic phases are dried over magnesium sulphate then the solvent eliminated under vacuum. The residue is chromatographed on silicagel eluting with a gradient of heptane (100%) to heptane-ethyl acetate (50-50). 25 mg (Yield=25%) of the expected product is obtained in the form of oil.

Workup

  1. temperatureis heated
  2. temperatureunder reflux for 3 hours
  3. temperatureAfter cooling down the reaction medium
  4. customThe organic phase is separated
  5. dry with materialThe combined organic phases are dried over magnesium sulphate
  6. customThe residue is chromatographed
  7. washon silicagel eluting with a gradient of heptane (100%) to heptane-ethyl acetate (50-50)

Sources & evidence

ORD record
ord-ef2a2387e6b74388b3df79b31afcd2ac
Source dataset
uspto-grants-2009_09
Patent number
US07582640B2

Reaction notes

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