Triethylamine → 4-[(2-Ethoxycarbonyl-ethyl)-indan-5-yl-amino]-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester

HRID 12330

Reaction equation

HRID 12330 reaction equation
[CH2:1]([O:3][C:4](=[O:17])[CH2:5][CH2:6][NH:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[CH2:13][CH2:12][CH2:11]2)[CH3:2].Cl[C:19]1[C:24]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:23][N:22]=[C:21]([S:30][CH3:31])[N:20]=1.C(N(CC)CC)C>C(O)CCC>[CH2:28]([O:27][C:25]([C:24]1[C:19]([N:7]([CH2:6][CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:17])[C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[CH2:13][CH2:12][CH2:11]3)=[N:20][C:21]([S:30][CH3:31])=[N:22][CH:23]=1)=[O:26])[CH3:29]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 800084-Chloro-2-(methylthio)pyrimidine-5-carboxylic acid ethyl esterHCID 252228753-(Indan-5-ylamino)-propionic acid ethyl ester

Product 1

HCID 252228764-[(2-Ethoxycarbonyl-ethyl)-indan-5-yl-amino]-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl esterYield 90%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

To a solution of 3-(indan-5-ylamino)-propionic acid ethyl ester (5 g, 21.4 mmol) and ethyl 4-chloro-2-methylthio-5-pyrimidinecarboxylate (5 g, 21.4 mmol) in 40 mL of n-butanol was added triethylamine (3 mL, 21.4 mmol). The solution was stirred at rt for 2 days. The solvent was removed under vacuum. The residue was extracted into EtOAc, washed with water, brine and then dried with Na2SO4. Removal of the solvent and chromatography on silica, eluting with EtOAc/hexanes (1:10-1:6, v/v), gave 8.2 g (90%) of the titled compound as a white solid. 1H NMR (300 MHz, CDCl3) δ (ppm): 8.22 (s, 1H), 7.16 (d, J=7.6 Hz, 1H), 6.95 (s, 1H), 6.87 (d, J=7.6 Hz, 1H), 4.35 (t, 2H), 3.55 (q, 2H), 2.82 (m, 4H), 2.69 (t, 2H), 2.58 (s, 3H), 2.06 (m, 2H), 1.20 (t, 3H), 1.02 (t, 3H).

Workup

  1. customThe solvent was removed under vacuum
  2. extractionThe residue was extracted into EtOAc
  3. washwashed with water, brine
  4. dry with materialdried with Na2SO4
  5. customRemoval of the solvent and chromatography on silica
  6. washeluting with EtOAc/hexanes (1:10-1:6, v/v)

Sources & evidence

ORD record
ord-388c20312aad4c688e3949a8286aa8af
Source dataset
uspto-grants-2010_06
Patent number
US07728003B2

Linked notes

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