Phenyl (1-phenyl-1H-pyrazol-5-yl)carbamate → (8aS)-1,3-dioxo-2-[(1S,2R)-2-phenylcyclopropyl]-N-(1-phenyl-1H-pyrazol-5-yl)hexahydroimidazo[1,5-a]pyrazine-7(1H)-carboxamide

HRID 1260472Notes

Reaction equation

HRID 1260472 reaction equation
Cl.[C:2]1([C@H:8]2[CH2:10][C@@H:9]2[N:11]2[C:19](=[O:20])[C@@H:14]3[CH2:15][NH:16][CH2:17][CH2:18][N:13]3[C:12]2=[O:21])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:22]1([N:28]2[C:32]([NH:33][C:34](=O)[O:35]C3C=CC=CC=3)=[CH:31][CH:30]=[N:29]2)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C(Cl)Cl>[O:20]=[C:19]1[C@@H:14]2[CH2:15][N:16]([C:34]([NH:33][C:32]3[N:28]([C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)[N:29]=[CH:30][CH:31]=3)=[O:35])[CH2:17][CH2:18][N:13]2[C:12](=[O:21])[N:11]1[C@H:9]1[CH2:10][C@@H:8]1[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 57925698Phenyl (1-phenyl-1H-pyrazol-5-yl)carbamateHCID 67300061(8aS)-2-[(1S,2R)-2-Phenylcyclopropyl]tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione HCl salt

Product 1

HCID 56662793(8aS)-1,3-dioxo-2-[(1S,2R)-2-phenylcyclopropyl]-N-(1-phenyl-1H-pyrazol-5-yl)hexahydroimidazo[1,5-a]pyrazine-7(1H)-carboxamideYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Example 4, D2 (1 eq) was dissolved in DCM (0.1M), F3 (1.5 eq) and TEA (1.5 eq) were added and the reaction was stirred at RT 6 h. The reaction was diluted with DCM and washed with water and brine, dried and concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel eluting with 10-100% EtOAc/petroleum ether to afford the title compound in 85% yield. 1H NMR (400 MHz, DMSO-d6, 300K) δ 8.91 (1H, s), 7.62 (1H, d, J=1.7 Hz), 7.54-7.47 (4H, m), 7.37 (1H, m), 7.30 (2H, m), 7.22-7.20 (3H, m), 6.31 (1H, d, J=1.7 Hz), 4.24 (1H, m), 4.02-3.96 (2H, m), 3.87 (1H, m), 2.97 (1H, m), 2.84 (2H, m), 2.67 (1H, m), 2.38 (1H, m), 1.52-1.48 (1H, m), 1.40 (1H, m). MS (ES+) C25H24N6O3 requires 456, found: 457 (M+H+).

Workup

  1. washwashed with water and brine
  2. customdried
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product was purified by flash chromatography on silica gel eluting with 10-100% EtOAc/petroleum ether

Sources & evidence

ORD record
ord-711bf8d7397242fe89202c926ac99457
Source dataset
uspto-grants-2013_06
Patent number
US08470823B2

Reaction notes

Loading…