Chlorosuccinimide → 3-(1-tert-Butyloxycarbonyl-trans-4-(2-pyridyl)-pyrrolidin-3-ylamino)-6-chloro-1-ethoxycarbonylmethylpyrazinone

HRID 398402Notes

Reaction equation

HRID 398402 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]([NH:19][C:20]2[C:21](=[O:32])[N:22]([CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH:23]=[CH:24][N:25]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:33]N1C(=O)CCC1=O>C(Cl)(Cl)Cl>[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:20]2[C:21](=[O:32])[N:22]([CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[C:23]([Cl:33])=[CH:24][N:25]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 31398Chlorosuccinimide2×HCID 700234103-(1-tert-Butyloxycarbonyl-trans-4-(2-pyridyl)-pyrrolidin-3-ylamino)-1-ethoxycarbonylmethylpyrazinone

Product 1

HCID 700235713-(1-tert-Butyloxycarbonyl-trans-4-(2-pyridyl)-pyrrolidin-3-ylamino)-6-chloro-1-ethoxycarbonylmethylpyrazinone

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

A stirred solution of 3-(1-tert-butyloxycarbonyl-trans-4-(2-pyridyl)-pyrrolidin-3-ylamino)-1-ethoxycarbonylmethylpyrazinone from step 8 above (2.0 g, 4.5 mmol) and N-chlorosuccinimide (0.67 g, 5.0 mmol) in CHCl3 was heated to reflux for 6 h. More N-chlorosuccinimide (0.20 g, 1.5 mmol) was added and refluxing was continued for 12 h. The reaction was diluted with CHCl3 and washed with aqueous NaHCO3. The organic phase was separated, dried over Mg SO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography using a gradient elution of 25-50% EtOAc:hexanes to give the title compound as an amorphous solid (1.5 g, TLC Rf=0.5, 1:1 EtOAc:hexanes; HPLC RT=7.17 min, method A).

Workup

  1. temperatureto reflux for 6 h
  2. temperaturerefluxing
  3. washwashed with aqueous NaHCO3
  4. customThe organic phase was separated
  5. dry with materialdried over Mg SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash column chromatography
  9. washa gradient elution of 25-50% EtOAc

Sources & evidence

ORD record
ord-33dc4ca88968423aa3e7bc8d54b11c39
Source dataset
uspto-grants-2003_08
Patent number
US06610692B1

Reaction notes

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