Diisopropylethylamine → 3-(1-tert-Butyloxycarbonyl-trans-4-(2-pyridyl)-pyrrolidin-3-ylamino)-1-ethoxycarbonylmethylpyrazinone

HRID 398401Notes

Reaction equation

HRID 398401 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[C@H:10]([NH2:19])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:21]1[C:22](=[O:33])[N:23]([CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH:24]=[CH:25][N:26]=1.CCN(C(C)C)C(C)C>C1(C)C=CC=CC=1.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[C@H:10]([NH:19][C:21]2[C:22](=[O:33])[N:23]([CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH:24]=[CH:25][N:26]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 11807445(3-Bromo-2-oxo-2H-pyrazin-1-yl)-acetic Acid Ethyl EsterHCID 590855601-Tert-butyloxycarbonyl-trans-3-amino-4-(2-pyridyl)pyrrolidine

Product 1

HCID 700234103-(1-tert-Butyloxycarbonyl-trans-4-(2-pyridyl)-pyrrolidin-3-ylamino)-1-ethoxycarbonylmethylpyrazinone

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A stirred solution of 1-tert-butyloxycarbonyl-trans-3-amino-4-(2-pyridyl)pyrrolidine from step 7 above (2.5 g, 9.5 mmol), 3-bromo-1-ethoxycarbonylmethylpyrazinone (2.5 g, 9.5 mmol), and DIEA (1.9 mL, 11 mmol) in toluene (30 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 60-85% EtOAc:hexanes to give the title compound as an amorphous solid (3.4 g; TLC Rf=0.5, 4:1 EtOAc:hexanes; HPLC RT=5.92 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 60-85% EtOAc

Sources & evidence

ORD record
ord-9dbdf0ded0284b678088d648b80d3c24
Source dataset
uspto-grants-2003_08
Patent number
US06610692B1

Reaction notes

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