1,1'-Carbonyldiimidazole → (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 1260470Notes

Reaction equation

HRID 1260470 reaction equation
[C:1]1([N:7]2[C:11]([NH2:12])=[CH:10][CH:9]=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1N=CN([C:18](N2C=NC=C2)=[O:19])C=1.Cl.[C:26]1([C@H:32]2[CH2:34][C@@H:33]2[N:35]2[C:43](=[O:44])[C@@H:38]3[CH2:39][NH:40][CH2:41][CH2:42][N:37]3[C:36]2=[O:45])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>CC#N>[O:44]=[C:43]1[C@@H:38]2[CH2:39][N:40]([C:18]([NH:12][C:11]3[N:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[N:8]=[CH:9][CH:10]=3)=[O:19])[CH2:41][CH2:42][N:37]2[C:36](=[O:45])[N:35]1[C@H:33]1[CH2:34][C@@H:32]1[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 700061-Phenylpyrazol-5-ylamineHCID 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 33%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
80 °C

Procedure

F1 (1.0 eq.) was dissolved in MeCN (0.1M) and CDI (1.0 eq.) was added. The reaction was stirred at 80° C. for 5 h. After cooling at RT a solution of (D2) (0.5 eq.) and TEA (0.6 eq.) in MeCN (0.2M) was added dropwise. The mixture was stirred overnight. The solvents were removed under reduced pressure. Crude product was purified by preparative RP-HPLC using H2O (0.1% TFA) and MeCN (0.1% TFA) as eluents. The desired fractions were lyophilized to afford the title compound in 33% 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. additionwas added dropwise
  2. stirringThe mixture was stirred overnight
  3. customThe solvents were removed under reduced pressure
  4. customCrude product was purified by preparative RP-HPLC

Sources & evidence

ORD record
ord-26a1795f327d4cd7919fad5a22f53710
Source dataset
uspto-grants-2013_06
Patent number
US08470823B2

Reaction notes

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