N-methyl-2-pyrrolidone → Methyl 2-((2-chloropyrimidin-4-yl)amino)-2-methylbutanoate

HRID 2402563Notes

Reaction equation

HRID 2402563 reaction equation
[NH2:1][C:2]([CH3:9])([CH2:7][CH3:8])[C:3]([O:5][CH3:6])=[O:4].[Cl:10][C:11]1[N:16]=[C:15](Cl)[CH:14]=[CH:13][N:12]=1.CN1C(=O)CCC1>O>[Cl:10][C:11]1[N:16]=[C:15]([NH:1][C:2]([CH3:9])([CH2:7][CH3:8])[C:3]([O:5][CH3:6])=[O:4])[CH:14]=[CH:13][N:12]=1

Participants

5

Reactant 3

HCID 13387N-methyl-2-pyrrolidoneHCID 775312,4-DichloropyrimidineHCID 4715131Methyl 2-amino-2-methylbutanoate

Product 1

HCID 86682097Methyl 2-((2-chloropyrimidin-4-yl)amino)-2-methylbutanoateYield 98.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A 250 mL flask was charged with methyl 2-amino-2-methylbutanoate (8.4 g, 54.4 mmol), 2,4-dichloropyrimidine (8.9 g, 59.8 mmol), TEA (5.5 g, 54.4 mmol) and 80 mL NMP. The reaction mixture was heated to 80° C. for ˜18 hours. After cooling, water (300 mL) was added and the mixture extracted with MTBE. The organic extracts were washed with water and dried over sodium sulfate. Filtration and evaporation under vacuum afforded 13 g of an orange oil which was purified by flash chromatography, (0-100% ethyl acetate-hexane affording 4.6 g (34%) methyl 2-((2-chloropyrimidin-4-yl)amino)-2-methylbutanoate as an oil. 1H NMR: (CDCl3) δ 8.05-7.88 (m, 1H), 6.28 (δ, 1H), 5.95 (δ, 1H), 4.2-4.0 (g, 1H), 3.86 (m, 1H), 2.46 (m, 1H), 2.10 (m, 1H), 2.01 (m, 1H), 1.72 (m, 3H), 0.89 (m, 3H). m/e, m+1 244.1

Workup

  1. temperatureAfter cooling
  2. extractionthe mixture extracted with MTBE
  3. washThe organic extracts were washed with water
  4. dry with materialdried over sodium sulfate
  5. filtrationFiltration and evaporation under vacuum

Sources & evidence

ORD record
ord-20ef4051d6e54c36b90c5d86b02237e0
Source dataset
uspto-grants-2014_08
Patent number
US08796453B2

Reaction notes

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