Dimethylformamide → 8-[(3S,4S)-1-(2-cyclopropyl-acetyl)-4-phenyl-pyrrolidin-3-ylmethyl]-2-(4-methoxy-benzyl)-2,8-diaza-spiro[4.5]decan-1-one

HRID 1182170Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1182170
[CH3:1][O:2][C:3]1[CH:32]=[CH:31][C:6]([CH2:7][N:8]2[CH2:12][CH2:11][C:10]3([CH2:17][CH2:16][N:15]([CH2:18][C@@H:19]4[C@@H:23]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)[CH2:22][NH:21][CH2:20]4)[CH2:14][CH2:13]3)[C:9]2=[O:30])=[CH:5][CH:4]=1.[CH:33]1([CH2:36][CH2:37]C(O)=O)[CH2:35][CH2:34]1.CC(C)N=C=NC(C)C.CN(C=[O:54])C>CN(C1C=CN=CC=1)C>[CH:33]1([CH2:36][C:37]([N:21]2[CH2:22][C@H:23]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[C@@H:19]([CH2:18][N:15]3[CH2:16][CH2:17][C:10]4([C:9](=[O:30])[N:8]([CH2:7][C:6]5[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:32][CH:31]=5)[CH2:12][CH2:11]4)[CH2:13][CH2:14]3)[CH2:20]2)=[O:54])[CH2:34][CH2:35]1

Komponenten

6

Edukt 4

HCID 6228DimethylformamideHCID 12734DiisopropylcarbodiimideHCID 27580133-Cyclopropylpropanoic acidHCID 114646642-(4-Methoxy-benzyl)-8-((3R,4S)-4-phenyl-pyrrolidin-3-ylmethyl)-2,8-diaza-spiro[4.5]decan-1-one

Produkt 1

HCID 111915488-[(3S,4S)-1-(2-cyclopropyl-acetyl)-4-phenyl-pyrrolidin-3-ylmethyl]-2-(4-methoxy-benzyl)-2,8-diaza-spiro[4.5]decan-1-oneAusbeute 72 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 142844-(Dimethylamino)pyridineKatalysator

Versuchsvorschrift

To 100 mg (0.23 mmol) of 2-(4-methoxy-benzyl)-8-((3R,4S)-4-phenyl-pyrrolidin-3-ylmethyl)-2,8-diaza-spiro[4.5]decan-1-one in DMF (1 mL) was added cyclopropylmethylacetic acid (39 mg, 0.311 mmol), DIC (31 μL, 0.311 mmol) and DMAP (8 mg, 0.065 mmol) and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated and purified by flash silica chromatography eluting first with ethyl acetate:hexanes (20%-100%) and then with methanol:dichloromethane (1:25) to give 116 mg (72%) of 8-[(3S,4S)-1-(2-cyclopropyl-acetyl)-4-phenyl-pyrrolidin-3-ylmethyl]-2-(4-methoxy-benzyl)-2,8-diaza-spiro[4.5]decan-1-one. The compound was then dissolved in methanol (2 mL) and HCl (aq., 0.2M, 3 mL) and stirred for 10 minutes. The solvent was removed in vacuo, and the solution lyophilized to give the Compound 117 (120 mg, 95%).

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated
  2. custompurified by flash silica chromatography
  3. washeluting first with ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-1de0df9698c7460eb6b9b3dad3218d28
Quelldatensatz
uspto-grants-2007_10
Patentnummer
US07288548B2

Notizen zur Reaktion

Wird geladen…