Guanidine Hydrochloride → 2-Amino-6-(tetrahydro-furan-3-yl)-3H-pyrimidin-4-one

HRID 1020763

반응식

HRID 1020763 반응식
C([O:3][C:4](=O)[CH2:5][C:6](=O)[CH:7]1[CH2:11][CH2:10][O:9][CH2:8]1)C.Cl.[NH2:15][C:16]([NH2:18])=[NH:17].CC(C)([O-])C.[K+]>CO.O>[NH2:17][C:16]1[NH:18][C:4](=[O:3])[CH:5]=[C:6]([CH:7]2[CH2:11][CH2:10][O:9][CH2:8]2)[N:15]=1

참가 물질

6

반응물 3

HCID 5742Guanidine HydrochlorideHCID 22831881Ethyl 3-oxo-3-(oxolan-3-yl)propanoateHCID 23665647Potassium tert-butoxide

생성물 1

HCID 1363801612-Amino-6-(tetrahydro-furan-3-yl)-3H-pyrimidin-4-one수율 51.9%

시약·촉매·용매 2

HCID 887Methanol용매HCID 962Water용매

반응 조건

온도
80 °C

실험 절차

To a solution of 3-oxo-3-(tetrahydro-furan-3-yl)-propionic acid ethyl ester (4.0 g, 21.5 mmol) and guanidine hydrochloride (2.6 g, 27.2 mmol) in MeOH (125 mL) at 23° C. was added potassium tert-butoxide in portions (3.4 g, 30.3 mmol) over 5 min. The reaction was heated at 80° C. for 18 h. The mixture was filtered while warm to remove insoluble salts, and the filtrate was concentrated to afford an oil which was diluted with water (˜25 mL) and extracted with EtOAc (8×50 mL). The combined organic layers were washed with satd. aq. NaCl, dried, and concentrated to give a residue. The aqueous portion was concentrated to afford a solid residue that was collected and rinsed with MeOH. The residue and solid materials were combined and chromatographed (2 M NH3 in MeOH/EtOAc) to provide 2.02 g of product as a white solid (51%). MS (ESI): mass calcd. for: C8H11N3O2, 181.1; m/z found, 182.2 [M+H]+. 1H NMR (CD3OD): 5.66 (br s, 1H), 3.93-4.01 (m, 2H), 3.75-3.85 (m, 2H), 3.28-3.31 (m, 2H), 3.16-3.24 (m, 1H), 2.18-2.27 (m, 1H), 2.05-2.15 (m, 1H).

후처리

  1. filtrationThe mixture was filtered
  2. temperaturewhile warm
  3. customto remove insoluble salts
  4. concentrationthe filtrate was concentrated
  5. customto afford an oil which
  6. extractionextracted with EtOAc (8×50 mL)
  7. washThe combined organic layers were washed with satd
  8. dry with materialaq. NaCl, dried
  9. concentrationconcentrated
  10. customto give a residue
  11. concentrationThe aqueous portion was concentrated
  12. customto afford a solid residue that
  13. customwas collected
  14. washrinsed with MeOH
  15. customchromatographed (2 M NH3 in MeOH/EtOAc)

출처 및 근거

ORD 기록
ord-c3da9363038e47baaf68aaa58eb29f19
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08716475B2

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