Diisopropylethylamine → HCID 59506511, compound

HRID 1798897Notes

Reaction equation

HRID 1798897 reaction equation
Cl[C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:6]([Cl:13])[N:5]=[C:4]([S:14][CH3:15])[N:3]=1.C(N(C(C)C)CC)(C)C.[C:25]1([NH:31][CH2:32][CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>CN(C=O)C>[Cl:13][C:6]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:2]([N:31]([CH2:32][CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[N:3]=[C:4]([S:14][CH3:15])[N:5]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 533817Ethyl 4,6-dichloro-2-(methylsulfanyl)pyrimidine-5-carboxylateHCID 10910393beta-Alanine, N-phenyl-, ethyl ester

Product 1

HCID 59506511HCID 59506511, compoundYield 80.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
100 °C

Procedure

To a solution of ethyl 4,6-dichloro-2-(methylthio)pyrimidine-5-carboxylate (47.0 g, 175.94 mmol) in DMF (470 mL) and diisopropylethylamine (100.43 mL, 582.7 mmol) was added ethyl 3-(phenylamino)propanoate (31.0 g, 160.4 mmol). The reaction mixture was heated to 100° C. and stirred for 7 h. Upon completion of the reaction (monitored by TLC), DMF was evaporated under reduced pressure and water (250 mL) was then added. The reaction mixture was extracted using EtOAc (200 mL×3). The combined organic layer was washed with water (500 mL×2), brine (500 mL), dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to give a residue. The residue was purified by silica gel column chromatography (using 0-20% Ethyl acetate in hexane) to afford ethyl 4-chloro-6-((3-ethoxy-3-oxopropyl)(phenyl)amino)-2-(methylthio)pyrimidine-5-carboxylate (55 g, 80.8% yield). 1H NMR (400 MHz, CDCl3): δ 7.38 (t, J=8.0 Hz, 2H), 7.31 (d, J=7.6 Hz, 1H), 7.18 (d, J=7/2 Hz, 2H), 4.26 (t, J=7.6 Hz, 2H), 4.05 (q, J=7.2 Hz, 2H), 3.47 (q, J=7.2 Hz, 2H), 2.68 (t, J=7.6 Hz, 2H), 2.54 (s, 3H), 1.19 (t, J=7.2 Hz, 3H), 1.08 (t, J=7.2 Hz, 3H). LCMS [M+H]; 424

Workup

  1. customwas evaporated under reduced pressure and water (250 mL)
  2. additionwas then added
  3. extractionThe reaction mixture was extracted
  4. washThe combined organic layer was washed with water (500 mL×2), brine (500 mL)
  5. dry with materialdried over anhydrous sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto give a residue
  9. customThe residue was purified by silica gel column chromatography (using 0-20% Ethyl acetate in hexane)

Sources & evidence

ORD record
ord-54dc80ad94a6471791d7fa54a85b6333
Source dataset
uspto-grants-2013_01
Patent number
US08343983B2

Reaction notes

Loading…