Cyclopropanecarboxylic acid → (3aS,7aS)-1-[1-[1-(cyclopropanecarbonyl)-4-methyl-4-piperidyl]-4-piperidyl]-3a,4,5,6,7,7a-hexahydro-3H-benzoimidazol-2-one

HRID 1642475Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1642475
[CH3:1][C:2]1([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[C@H:18]4[CH2:19][CH2:20][CH2:21][CH2:22][C@@H:17]4[NH:16][C:15]3=[O:23])[CH2:10][CH2:9]2)[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[CH:24]1([C:27](O)=[O:28])[CH2:26][CH2:25]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C>[CH:24]1([C:27]([N:5]2[CH2:6][CH2:7][C:2]([N:8]3[CH2:13][CH2:12][CH:11]([N:14]4[C@H:18]5[CH2:19][CH2:20][CH2:21][CH2:22][C@@H:17]5[NH:16][C:15]4=[O:23])[CH2:10][CH2:9]3)([CH3:1])[CH2:3][CH2:4]2)=[O:28])[CH2:26][CH2:25]1

Komponenten

6

Edukt 4

HCID 15655Cyclopropanecarboxylic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57619802(3aS,7aS)-1-[1-(4-methyl-4-piperidyl)-4-piperidyl]-3a,4,5,6,7,7a-hexahydro-3H-benzoimidazol-2-one

Produkt 1

HCID 25221109(3aS,7aS)-1-[1-[1-(cyclopropanecarbonyl)-4-methyl-4-piperidyl]-4-piperidyl]-3a,4,5,6,7,7a-hexahydro-3H-benzoimidazol-2-oneAusbeute 61 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To the solution (3aS,7aS)-1-[1-(4-methyl-4-piperidyl)-4-piperidyl]-3a,4,5,6,7,7a-hexahydro-3H-benzoimidazol-2-one (99 mg, 0.25 mmol) in dry DMF (3 mL) was added cyclopropanecarboxylic acid (26 mg, 0.3 mmol) followed by HATU (114 mg, 0.3 mmol) and diisopropylethylamine (0.10 mL, 0.5 mmol) and stirred at room temperature for 1 h. The solvent was removed in vacuo, dichloromethane added (15 mL), washed with saturated NaHCO3 (10 mL) and brine (10 mL), dried over Na2SO4 and concentrated in vacuo. The residue was purified with preparative LC/MS (high pH) to yield the title compound (59 mg, 61%) as white powder. 1H NMR (400 MHz, METHANOL-D4) δ ppm 0.71-0.89 (m, 4H), 1.00 (s, 3H), 1.28-1.46 (m, 5H), 1.50-1.68 (m, 2H), 1.68-1.89 (m, 8H), 1.89-2.00 (m, 2H), 2.11-2.31 (m, 2H), 2.86-3.02 (m, 2H), 3.02-3.14 (m, 2H), 3.47-3.70 (m, 4H), 3.75-3.91 (m, 1H). MS (M+1): 389.2.

Aufarbeitung

  1. customThe solvent was removed in vacuo, dichloromethane
  2. additionadded (15 mL)
  3. washwashed with saturated NaHCO3 (10 mL) and brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified with preparative LC/MS (high pH)

Quellen und Nachweise

ORD-Eintrag
ord-6e0235bcbc65470997525ecd5650c228
Quelldatensatz
uspto-grants-2012_02
Patentnummer
US08119661B2

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