1-Methylcyclopropanecarboxylic acid → (3aS,7aS)-1-(1'-(1-methylcyclopropanecarbonyl)-1,4'-bipiperidin-4-yl)hexahydro-1H-benzo[d]imidazol-2(3H)-one

HRID 2421078Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2421078
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:25][C:26]1([C:29]([OH:31])=O)[CH2:28][CH2:27]1.C(N(CC)C(C)C)(C)C.[N:41]1([CH:57]2[CH2:62][CH2:61][NH:60][CH2:59][CH2:58]2)[CH2:46][CH2:45][CH:44]([N:47]2[C@H:51]3[CH2:52][CH2:53][CH2:54][CH2:55][C@@H:50]3[NH:49][C:48]2=[O:56])[CH2:43][CH2:42]1>CC(N(C)C)=O>[CH3:25][C:26]1([C:29]([N:60]2[CH2:61][CH2:62][CH:57]([N:41]3[CH2:42][CH2:43][CH:44]([N:47]4[C@H:51]5[CH2:52][CH2:53][CH2:54][CH2:55][C@@H:50]5[NH:49][C:48]4=[O:56])[CH2:45][CH2:46]3)[CH2:58][CH2:59]2)=[O:31])[CH2:28][CH2:27]1

Komponenten

6

Edukt 4

HCID 813261-Methylcyclopropanecarboxylic acidHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 24882730(3aS,7aS)-1-[1-(4-piperidyl)-4-piperidyl]-3a,4,5,6,7,7a-hexahydro-3H-benzoimidazol-2-one

Produkt 1

HCID 24883160(3aS,7aS)-1-(1'-(1-methylcyclopropanecarbonyl)-1,4'-bipiperidin-4-yl)hexahydro-1H-benzo[d]imidazol-2(3H)-oneAusbeute 20,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel

Versuchsvorschrift

HBTU (284 mg, 0.75 mmol) was added to a solution of 1-methylcyclopropanecarboxylic acid (75 mg, 0.75 mmol), N,N-diisopropylethyl amine (194 mg, 1.50 mmol) and (3aS,7aS)-1-(1,4′-bipiperidin-4-yl)hexahydro-1H-benzo[d]imidazol-2(3H)-one (153.22 mg, 0.50 mmol) in DMA (10 mL) and stirred at room temperature for overnight. Concentrated in vacuo, diluted in dichloromethane (50 ml) and washed with sat. NaHCO3 (10 mL). The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by high pH Prep LCMS to give the titled compound (40 mg, 20.6%). 1H NMR (400 MHz, CHLOROFORM-D): δ ppm 0.51-0.59 (m, 2H) 0.86-0.94 (m, 2H) 1.30 (s, 3H) 1.33-1.45 (m, 6H) 1.68 (s, 1H) 1.74-1.84 (m, 7H) 1.96 (d, J=10.16 Hz, 1H) 2.21-2.32 (m, 3H) 2.48 (t, J=11.13 Hz, 1H) 2.76 (s, 1H) 2.92-3.03 (m, 4H) 3.71-3.81 (m, 1H) 4.49 (s, 3H). MS (M+1): 389.2

Aufarbeitung

  1. concentrationConcentrated in vacuo
  2. additiondiluted in dichloromethane (50 ml)
  3. washwashed with sat. NaHCO3 (10 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by high pH Prep LCMS

Quellen und Nachweise

ORD-Eintrag
ord-1ac37ebd115f456196783f2d95cb1a8a
Quelldatensatz
uspto-grants-2011_06
Patentnummer
US07956069B2

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