Diisopropylethylamine → (1,1-dimethylethyl) 3-[(6-chloro-5-ethyl-4-pyrimidinyl)amino]-N-[(phenylmethoxy)carbonyl]alaninate

HRID 729739Notes

Reaction equation

HRID 729739 reaction equation
C(N(C(C)C)CC)(C)C.Cl[C:11]1[C:16]([CH2:17][CH3:18])=[C:15]([Cl:19])[N:14]=[CH:13][N:12]=1.[CH3:20][C:21]([O:24][C:25](=[O:40])[C@H:26]([CH2:38][NH2:39])[NH:27][C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29])([CH3:23])[CH3:22].C(=O)(O)[O-].[Na+]>CN(C)C=O.C(OCC)(=O)C.O>[CH3:23][C:21]([O:24][C:25](=[O:40])[C@H:26]([CH2:38][NH:39][C:11]1[C:16]([CH2:17][CH3:18])=[C:15]([Cl:19])[N:14]=[CH:13][N:12]=1)[NH:27][C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29])([CH3:20])[CH3:22]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 10803731(S)-tert-Butyl 3-amino-2-(((benzyloxy)carbonyl)amino)propanoateHCID 21828432HCID 21828432, compound

Product 1

HCID 12094339(1,1-dimethylethyl) 3-[(6-chloro-5-ethyl-4-pyrimidinyl)amino]-N-[(phenylmethoxy)carbonyl]alaninateYield 72%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

10 ml of diisopropylethylamine is added to a mixture of 3.8 g (21 mmoles) of 4,6-dichloro-5-ethyl-pyrimidine and 4.4 g (15 mmoles) of (1,1-dimethylethyl)3-amino-N-[(phenylmethoxy)carbonyl]alaninate (prepared according to J. Med. Chem. (2001), 44(8), 1158-1176) in 50 ml of dimethylformamide, then this mixture is heated at 120° C. for 6 hours. Then the dimethylformamide is eliminated under vacuum and the residue is taken up in a mixture of ethyl acetate, water and a saturated solution of sodium bicarbonate. The organic phase is decanted then dried over magnesium sulphate and the solvent is eliminated by evaporation under vacuum. The residue is chromatographed on silicagel eluting with a gradient of 100% heptane to heptane-ethyl acetate 50-50. 4.7 g (Yield=70%) of expected product is obtained in the form of an oil.

Workup

  1. customThe organic phase is decanted
  2. dry with materialthen dried over magnesium sulphate
  3. customthe solvent is eliminated by evaporation under vacuum
  4. customThe residue is chromatographed
  5. washon silicagel eluting with a gradient of 100% heptane to heptane-ethyl acetate 50-50

Sources & evidence

ORD record
ord-b6c00ad528bb43b2b4b438252c37308f
Source dataset
uspto-grants-2009_09
Patent number
US07582640B2

Reaction notes

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