2-Aminothiazole → 7-(Chloromethyl)-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one

HRID 1642369Notes

Reaction equation

HRID 1642369 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[CH:5][N:6]=1.[Cl:7][CH2:8][C:9](=O)[CH2:10][C:11](OCC)=[O:12].[OH-].[Na+]>>[Cl:7][CH2:8][C:9]1[N:1]=[C:2]2[S:3][CH:4]=[CH:5][N:6]2[C:11](=[O:12])[CH:10]=1

Participants

4

Reactant 3

HCID 21552-AminothiazoleHCID 14798Sodium HydroxideHCID 69484Ethyl 4-chloroacetoacetate

Product 1

HCID 20635977-(Chloromethyl)-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-oneYield 25.9%

Conditions

Temperature
110 °C

Procedure

A solution of 2-aminothiazole (5.0 g, 49.993 mmol) in polyphosphoric acid (40.0 g) was treated with ethyl chloroacetoacetate (11.176 g, 67.866 mmol) and heated at 110° C. for 5.0 h. The reaction mixture was cooled to room temperature and adjusted to pH 7 with 10% aq. NaOH. The solid formed was filtered and purified by column chromatography using ethyl acetate in dichloromethane as solvent to afford 2.6 g of the desired compound as a brown solid: 1H NMR (300 MHz, DMSO-d6) δ 4.59 (s, 2H), 6.41 (s, 1H), 7.56 (d, J=4.8 Hz, 1H), 8.03 (d, J=4.8 Hz, 1H); ESI-MS (m/z) 200.42 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe solid formed
  3. filtrationwas filtered
  4. custompurified by column chromatography

Sources & evidence

ORD record
ord-0f9e2924e62c4527a082eee9be3cd327
Source dataset
uspto-grants-2012_02
Patent number
US08119647B2

Reaction notes

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