Diisopropylethylamine → tert-butyl 1,3-dioxo-2-[trans-2-phenylcyclopropyl]hexahydroimidazo[1,5-a]pyrazine-7(1H)-carboxylate

HRID 1260463Notes

Reaction equation

HRID 1260463 reaction equation
[N:1]1([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6][CH2:5][NH:4][CH:3]([C:7]([O:9]C)=O)[CH2:2]1.[C:18]1([C@@H:24]2[CH2:26][C@H:25]2[N:27]=[C:28]=[O:29])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.CCN(C(C)C)C(C)C>C1(C)C=CC=CC=1>[O:9]=[C:7]1[CH:3]2[CH2:2][N:1]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6][CH2:5][N:4]2[C:28](=[O:29])[N:27]1[C@@H:25]1[CH2:26][C@H:24]1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 255285trans-2-Phenylcyclopropyl isocyanateHCID 27568191-tert-Butyl 3-methyl piperazine-1,3-dicarboxylate

Product 1

HCID 67300259tert-butyl 1,3-dioxo-2-[trans-2-phenylcyclopropyl]hexahydroimidazo[1,5-a]pyrazine-7(1H)-carboxylateYield 60%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To A3 in toluene (0.4M) was added dropwise trans-2-phenylcyclopropyl isocyanate (1.05 eq.). The mixture was stirred O/N at rt. DIPEA (1.5 eq.) was added and the mixture refluxed for 20 h. The organic phase was washed with phosphate buffer (2×200 mL, 0.75 M NaH2PO4, pH˜4.5) and the solvent removed under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with 20-100% EtOAc/petroleum ether to give the title compound in 60% yield. MS (ES+) C20H25N3O4 requires 371, found: 394 (M+Na)+.

Workup

  1. temperaturethe mixture refluxed for 20 h
  2. washThe organic phase was washed with phosphate buffer (2×200 mL, 0.75 M NaH2PO4, pH˜4.5)
  3. customthe solvent removed under reduced pressure
  4. customThe residue was purified by column chromatography on silica gel
  5. washeluting with 20-100% EtOAc/petroleum ether

Sources & evidence

ORD record
ord-b5e88df092df44849a39f0f0487209d7
Source dataset
uspto-grants-2013_06
Patent number
US08470823B2

Reaction notes

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