반응 #509179

반응 방정식

5-iodo-6-methyl-N4-(tetrahydro-2H-pyran-4-yl)pyrimidine-2,4-diamine

triethylamine

ethyl acrylate

→

(E)-ethyl 3-(2-amino-4-methyl-6-(tetrahydro-2H-pyran-4-ylamino)pyrimidin-5-yl)acrylate

용매

DMF

반응 조건

후처리

1. 1
   기타The reaction was purged with nitrogen for 5 min.
2. 2
   workup.ADDITIONPd(PPh3)4 (10 mol %, 3.50 g) was added
3. 3
   온도cooled to room temperature
4. 4
   기타Nearly all DMF was evaporated under reduced pressure
5. 5
   workup.ADDITIONThe reaction was poured into ethyl acetate (500 mL) and H2O (300 mL)
6. 6
   기타The organic layer collected
7. 7
   건조dried over anhydrous sodium sulfate
8. 8
   농축concentrated in vacuo
9. 9
   기타to afford the crude product
10. 10
    기타The product was purified by a flash chromatography (70% ethyl acetate/hexanes to 10% EtOH/ethyl acetate)

실험 절차

To a solution of 5-iodo-6-methyl-N4-(tetrahydro-2H-pyran-4-yl)pyrimidine-2,4-diamine (10.0 g, 30.0 mmol) in DMF (200 mL) was added triethylamine (12.50 mL, 90.0 mmol) and ethyl acrylate (9.80 mL, 90.0 mmol) successively at room temperature. The reaction was purged with nitrogen for 5 min. and Pd(PPh3)4 (10 mol %, 3.50 g) was added. The reaction was heated to 95° C., stirred for overnight under nitrogen, and then cooled to room temperature. Nearly all DMF was evaporated under reduced pressure. The reaction was poured into ethyl acetate (500 mL) and H2O (300 mL). The organic layer collected and dried over anhydrous sodium sulfate, and concentrated in vacuo to afford the crude product. The product was purified by a flash chromatography (70% ethyl acetate/hexanes to 10% EtOH/ethyl acetate) to afford (E)-ethyl 3-(2-amino-4-methyl-6-(tetrahydro-2H-pyran-4-ylamino)pyrimidin-5-yl)acrylate, as a light yellow semicrystal (yield: 6.85 g, 75.0%). LC/MS: calculated for C15H22N4O3 (306.17). found: 307.2 (MH+). HPLC analytical purity: >97.0%.

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