Diisopropylethylamine → 3-(trans-3-Cyclopropylmethoxytetrahydrofuran-4-ylamino)-1-ethoxycarbonylmethylpyrazinone

HRID 398392Notes

Reaction equation

HRID 398392 reaction equation
[CH:1]1([CH2:4][O:5][C@H:6]2[C@H:10]([NH2:11])[CH2:9][O:8][CH2:7]2)[CH2:3][CH2:2]1.Br[C:13]1[C:14](=[O:25])[N:15]([CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:16]=[CH:17][N:18]=1.CCN(C(C)C)C(C)C>C1(C)C=CC=CC=1.CCOC(C)=O>[CH:1]1([CH2:4][O:5][C@H:6]2[C@H:10]([NH:11][C:13]3[C:14](=[O:25])[N:15]([CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:16]=[CH:17][N:18]=3)[CH2:9][O:8][CH2:7]2)[CH2:2][CH2:3]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 11807445(3-Bromo-2-oxo-2H-pyrazin-1-yl)-acetic Acid Ethyl EsterHCID 70024767trans-3-Cyclopropylmethoxy-4-aminotetrahydrofuran

Product 1

HCID 700247483-(trans-3-Cyclopropylmethoxytetrahydrofuran-4-ylamino)-1-ethoxycarbonylmethylpyrazinone

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A stirred solution of trans-3-cyclopropylmethoxy-4-aminotetrahydrofuran from step 4 above (1.1 g, 7.0 mmol), 3-bromo-1-ethoxycarbonylmethylpyrazinone (1.8 g, 7.0 mmol), and DIEA (1.4 mL, 8.0 mmol) in toluene (20 mL) was heated to reflux for 24 h. The mixture was cooled to ambient temperature, diluted with EtOAc, and washed with aqueous NaHCO3. The organic phase was separated, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography using a gradient elution of 50-67% tOAc:hexanes to give the title compound as an amorphous solid (1.4 g; TLC Rf=0.4, 3:2 EtOAc:hexanes; HPLC RT=5.05 min, method A).

Workup

  1. temperatureto reflux for 24 h
  2. washwashed with aqueous NaHCO3
  3. customThe organic phase was separated
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography
  8. washa gradient elution of 50-67% tOAc

Sources & evidence

ORD record
ord-6507b36eaf1a481fb2ea6bf65b6a58c0
Source dataset
uspto-grants-2003_08
Patent number
US06610692B1

Reaction notes

Loading…