1,2-Dichloro-3-isocyanatobenzene → (8aS)-N-(2,3-dichlorophenyl)-1,3-dioxo-2-[(1S,2R)-2-phenylcyclopropyl]-5,6,8,8a-tetrahydroimidazo[1,5-a]pyrazine-7-carboxamide

HRID 1260468Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1260468
[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N:9]=[C:10]=[O:11].Cl.[C:13]1([C@H:19]2[CH2:21][C@@H:20]2[N:22]2[C:30](=[O:31])[C@@H:25]3[CH2:26][NH:27][CH2:28][CH2:29][N:24]3[C:23]2=[O:32])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[NH:9][C:10]([N:27]1[CH2:28][CH2:29][N:24]2[C:23](=[O:32])[N:22]([C@H:20]3[CH2:21][C@@H:19]3[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:30](=[O:31])[C@@H:25]2[CH2:26]1)=[O:11]

Komponenten

5

Edukt 3

HCID 330501,2-Dichloro-3-isocyanatobenzeneHCID 81531DiisopropylethylamineHCID 67300061(8aS)-2-[(1S,2R)-2-Phenylcyclopropyl]tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione HCl salt

Produkt 1

HCID 56676510(8aS)-N-(2,3-dichlorophenyl)-1,3-dioxo-2-[(1S,2R)-2-phenylcyclopropyl]-5,6,8,8a-tetrahydroimidazo[1,5-a]pyrazine-7-carboxamideAusbeute 67 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

2,3-Dichlorophenyl isocyanate (1.1 eq.) was added to a stirred solution of D2 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. The residue was purified by column chromatography on silica gel, eluting with 10-80% EtOAc/petroleum ether to give the title compound in 67% yield, 92% de by SFC. 1H NMR (400 MHz, DMSO-d6, 300K) δ 8.80 (1H, s), 7.45-7.42 (2H, m), 7.34-7.28 (3H, m), 7.23-7.18 (3H, m), 4.35 (1H, dd, J=12.9, 4.2 Hz), 4.14-4.09 (2H, m), 3.92 (1H, dd, J=13.0, 2.7 Hz), 3.07-2.99 (2H, m), 2.91 (1H, td, J=12.6, 3.0 Hz), 2.68 (1H, m), 2.39 (1H, ddd, J=9.8, 6.8, 3.2 Hz), 1.51 (1H, ddd, J=9.5, 5.7, 4.3 Hz), 1.41 (1H, dd, J=14.0, 7.1 Hz). MS (ES+) C22H20Cl2N4O3 requires 458, 460, found: 459, 461 (M+H+).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-78764fd43de144db8a4dc79d0d592f95
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08470823B2

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