Diisopropylethylamine → (8aS)-N-(4-Chloro-2-cyclopropylpyridin-3-yl)-1,3-dioxo-2-[(1S,2R)-2-phenylcyclopropyl]hexahydroimidazo[1,5-a]pyrazine-7(1H)-carboxamide

HRID 1260477Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1260477
[CH3:1][CH2:2][N:3](C(C)C)C(C)C.Cl[C:11]([Cl:21])(OC(=O)OC(Cl)(Cl)Cl)Cl.ClC1[C:28](Cl)=[CH:27][CH:26]=[CH:25][C:24]=1[NH:30][C:31]([N:33]1[CH2:38][CH2:37][N:36]2[C:39](=[O:52])[N:40]([C@H:43]3[CH2:45][C@@H:44]3[C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)[C:41](=[O:42])[C@@H:35]2[CH2:34]1)=[O:32].Cl.C1([C@H]2C[C@@H]2N2C(=O)[C@@H]3CNCCN3C2=O)C=CC=CC=1>C(Cl)Cl.ClCCCl>[Cl:21][C:11]1[CH:1]=[CH:2][N:3]=[C:25]([CH:26]2[CH2:28][CH2:27]2)[C:24]=1[NH:30][C:31]([N:33]1[CH2:38][CH2:37][N:36]2[C:39](=[O:52])[N:40]([C@H:43]3[CH2:45][C@@H:44]3[C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)[C:41](=[O:42])[C@@H:35]2[CH2:34]1)=[O:32]

Komponenten

7

Edukt 4

HCID 81531Diisopropylethylamine2×HCID 94429TriphosgeneHCID 56676510(8aS)-N-(2,3-dichlorophenyl)-1,3-dioxo-2-[(1S,2R)-2-phenylcyclopropyl]-5,6,8,8a-tetrahydroimidazo[1,5-a]pyrazine-7-carboxamideHCID 67300061(8aS)-2-[(1S,2R)-2-Phenylcyclopropyl]tetrahydroimidazo[1,5-a]pyrazine-1,3(2H,5H)-dione HCl salt

Produkt 1

HCID 67300227(8aS)-N-(4-Chloro-2-cyclopropylpyridin-3-yl)-1,3-dioxo-2-[(1S,2R)-2-phenylcyclopropyl]hexahydroimidazo[1,5-a]pyrazine-7(1H)-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 111,2-DichloroethaneLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

L1 (1.0 eq.) and DIPEA (5.0 eq.) in DCM (0.1M) was slowly added to an ice cooled solution of triphosgene (0.33 eq.) in DCM (0.1M). The reaction mixture was stirred 30 min at RT and slowly added to a solution of Example 4, D2 (0.5 eq) and DIPEA (0.5 eq) in DCE (0.1M). The reaction mixture was stirred 3 h at RT, volatiles were removed under reduced pressure and the 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 as a white powder. 1H-NMR (400 MHz, DMSO-d6, 300K) δ 8.80 (1H, br. s), 8.24 (1H, d, J=5.1 Hz), 7.34 (1H, d, J=5.1 Hz), 7.32-7.26 (2H, m), 7.25-7.17 (3H, m), 4.39 (1H, dd, J=4.1 and 13.0 Hz), 4.17-4.06 (2H, m), 3.97-3.90 (1H, m), 3.12-2.88 (3H, m), 2.72-2.65 (1H, m), 2.43-2.35 (1H, m), 2.30-2.20 (1H, m), 1.55-1.47 (1H, m), 1.45-1.38 (1H, m), 0.98-0.90 (4H, m). MS (ES) C24H24ClN5O3 requires: 465, found: 466, 468 (M+H)+.

Aufarbeitung

  1. stirringThe reaction mixture was stirred 3 h at RT
  2. customvolatiles were removed under reduced pressure
  3. customthe crude product was purified by preparative RP-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-016a66526bb04d488627c90309045fc1
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08470823B2

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