Isopropanol → 6'-[(3,3-Difluorocyclobutyl)methoxy]-4-methoxy-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazole]-4''(3''H)-thione

HRID 1468076Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1468076
[F:1][C:2]1([F:25])[CH2:5][CH:4]([CH2:6][O:7][C:8]2[CH:16]=[C:15]3[C:11]([CH2:12][C:13]4([CH2:22][CH2:21][CH:20]([O:23][CH3:24])[CH2:19][CH2:18]4)[C:14]3=[NH:17])=[CH:10][CH:9]=2)[CH2:3]1.C(OC)(OC)OC.CC(O)C.O=[C:38]([CH3:42])[C:39](=[S:41])[NH2:40]>CO.CCCCCCC.CCOC(C)=O>[F:1][C:2]1([F:25])[CH2:5][CH:4]([CH2:6][O:7][C:8]2[CH:16]=[C:15]3[C:11]([CH2:12][C:13]4([C:14]53[NH:40][C:39](=[S:41])[C:38]([CH3:42])=[N:17]5)[CH2:22][CH2:21][CH:20]([O:23][CH3:24])[CH2:19][CH2:18]4)=[CH:10][CH:9]=2)[CH2:3]1

Komponenten

8

Edukt 4

HCID 3776IsopropanolHCID 9005Trimethyl orthoformateHCID 207652372-Oxopropanethioamide2×HCID 867067236'-((3,3-difluorocyclobutyl)methoxy)-4-methoxyspiro[cyclohexane-1,2'-inden]-1'(3'H)-imine

Produkt 1

HCID 867067246'-[(3,3-Difluorocyclobutyl)methoxy]-4-methoxy-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazole]-4''(3''H)-thioneAusbeute 12 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 8900HeptaneLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

HCl (4 M in 1,4-dioxane, 4.13 mL, 16.5 mmol) was added to a solution of N-(5′-((3,3-difluorocyclobutyl)methoxy)-4-methoxyspiro[cyclohexane-1,2′-indene]-3′(1′H)-ylidene)-2-methylpropane-2-sulfinamide (Intermediate 18, 750 mg, 1.65 mmol) in anhydrous 1,4-dioxane (25 mL). A white precipitate formed immediately and the resulting cloudy mixture was stirred under a nitrogen atmosphere overnight. The mixture was diluted with NaHCO3 (aq.) and extracted with DCM. The organic phase was dried and concentrated, to yield 6′-((3,3-difluorocyclobutyl)methoxy)-4-methoxyspiro[cyclohexane-1,2′-inden]-1′(3′H)-imine (672 mg, 1.92 mmol). The imine, trimethyl orthoformate (0.557 mL, 5.08 mmol) and 2-propanol (5 mL) was placed into a MW tube and the mixture was heated at 60° C. in an oil bath. 2-oxopropanethioamide (Intermediate 1, 397 mg, 3.85 mmol) in MeOH (15 mL) was added and the resulting mixture was stirred overnight. The mixture was concentrated in vacuo. The product was isolated using column chromatography (0-50% EtOAc in heptane) to give 106 mg (12% yield) of the title compound. MS (ES+) m/z 435 [M+H]+.

Aufarbeitung

  1. concentrationThe mixture was concentrated in vacuo
  2. customThe product was isolated

Quellen und Nachweise

ORD-Eintrag
ord-abbc71761ad84c3f854d55136a54d790
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09000185B2

Notizen zur Reaktion

Wird geladen…