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

HRID 729740Notes

Reaction equation

HRID 729740 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[CH2:29][CH3:30].[NH:31]1[CH2:36][CH2:35][CH:34]([C:37]([O:39][CH3:40])=[O:38])[CH2:33][CH2:32]1.C(NCC)(C)C.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.O>[CH3:26][C:25]([O:24][C:22](=[O:23])[C@H:10]([CH2:9][NH:8][C:4]1[C:3]([CH2:29][CH3:30])=[C:2]([N:31]2[CH2:36][CH2:35][CH:34]([C:37]([O:39][CH3:40])=[O:38])[CH2:33][CH2:32]2)[N:7]=[CH:6][N:5]=1)[NH:11][C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13])([CH3:28])[CH3:27]

Participants

7

Reactant 4

HCID 88318IsopropylethylamineHCID 424914Methyl isonipecotateHCID 516892Sodium BicarbonateHCID 12094339(1,1-dimethylethyl) 3-[(6-chloro-5-ethyl-4-pyrimidinyl)amino]-N-[(phenylmethoxy)carbonyl]alaninate

Product 1

HCID 12094342(1,1-dimethylethyl) 3-[[5-ethyl-6-[4-(methoxycarbonyl)-1-piperidinyl]-4-pyrimidinyl]amino]-N-[(phenylmethoxy)carbonyl]alaninateYield 17%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 1.2 g (2.8 mmoles) of (1,1-dimethylethyl) 3-[(6-chloro-5-ethyl-4-pyrimidinyl)amino]-N-[(phenylmethoxy)carbonyl]alaninate, 5 ml of methyl 4-piperidinylcarboxylate and 1 ml of isopropylethylamine is heated between 110 and 120° C. for 4 hours. After cooling down to ambient temperature, the reaction medium is taken up in ethyl acetate, water and a saturated solution of sodium bicarbonate. The organic phase is separated, dried over magnesium sulphate then concentrated to dryness under vacuum. The residue is chromatographed on silicagel with a gradient of pure heptane to pure ethyl acetate. 260 mg (Yield=17%) of expected product is obtained in the form of an oil.

Workup

  1. temperatureis heated between 110 and 120° C. for 4 hours
  2. customThe organic phase is separated
  3. dry with materialdried over magnesium sulphate
  4. concentrationthen concentrated to dryness under vacuum
  5. customThe residue is chromatographed on silicagel with a gradient of pure heptane to pure ethyl acetate

Sources & evidence

ORD record
ord-48613cbee3b44d4abb5ed18a9101a72a
Source dataset
uspto-grants-2009_09
Patent number
US07582640B2

Reaction notes

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