Diisopropylethylamine → N-Biphenyl-2-yl-1,3-dioxo-2-[trans-2-phenylcyclopropyl]hexahydroimidazo[1,5-a]pyrazine-7(1H)-carboxamide

HRID 1260465Notes

Reaction equation

HRID 1260465 reaction equation
[C:1]1([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:2]([N:7]=[C:8]=[O:9])=[CH:3][CH:4]=[CH:5][CH:6]=1.[C:16]1([C@@H:22]2[CH2:24][C@H:23]2[N:25]2[C:33](=[O:34])[CH:28]3[CH2:29][NH:30][CH2:31][CH2:32][N:27]3[C:26]2=[O:35])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:1]1([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]([N:30]1[CH2:31][CH2:32][N:27]2[C:26](=[O:35])[N:25]([C@@H:23]3[CH2:24][C@H:22]3[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:33](=[O:34])[CH:28]2[CH2:29]1)=[O:9]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 2222801-Isocyanato-2-phenylbenzeneHCID 673000522-[trans-2-phenylcyclopropyl]tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione

Product 1

HCID 44634495N-Biphenyl-2-yl-1,3-dioxo-2-[trans-2-phenylcyclopropyl]hexahydroimidazo[1,5-a]pyrazine-7(1H)-carboxamideYield 76%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

[1,1′-Biphenyl]-2-yl-isocyanate (1.1 eq) was added to a stirred solution of A5 and DIPEA (3.0 eq) in DCM (0.09 M), and the mixture was stirred at RT for 1 h. The solvents were removed under reduced pressure and the residue was purified by column chromatography on silica gel, eluting with 10-80% EtOAc/petroleum ether to give the title compound in 76% yield. 1H NMR (400 MHz, DMSO-d6, 300K) δ 8.36 (1H, s), 7.43-7.38 (4H, m), 7.33-7.27 (7H, m), 7.20 (3H, m), 4.19 (1H, m), 3.93 (1H, m), 3.85-3.77 (2H, m), 2.86 (1H, m), 2.74 (2H, d, J=9.3 Hz), 2.67 (1H, m), 2.40-2.30 (1H, m), 1.58-1.48 (1H, m), 1.43-1.37 (1H, m). MS (ES+) C28H26N4O3 requires 466, found: 467 (M+H)+.

Workup

  1. customThe solvents were removed under reduced pressure
  2. customthe residue was purified by column chromatography on silica gel
  3. washeluting with 10-80% EtOAc/petroleum ether

Sources & evidence

ORD record
ord-d786d20b60ce4c3d8dff4a6a0686a3ae
Source dataset
uspto-grants-2013_06
Patent number
US08470823B2

Reaction notes

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