Ammonia → 6'-Bromo-4-(difluoromethyl)-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazol]-4''-amine

HRID 1965150

Reaktionsgleichung

Reaktionsgleichung von HRID 1965150
[Br:1][C:2]1[CH:24]=[C:23]2[C:5]([CH2:6][C:7]3([C:16]42[NH:20][C:19](=S)[C:18]([CH3:22])=[N:17]4)[CH2:12][CH2:11][CH:10]([CH:13]([F:15])[F:14])[CH2:9][CH2:8]3)=[CH:4][CH:3]=1.[NH3:25]>>[Br:1][C:2]1[CH:24]=[C:23]2[C:5]([CH2:6][C:7]3([C:16]42[N:20]=[C:19]([NH2:25])[C:18]([CH3:22])=[N:17]4)[CH2:12][CH2:11][CH:10]([CH:13]([F:15])[F:14])[CH2:9][CH2:8]3)=[CH:4][CH:3]=1

Komponenten

3

Edukt 2

HCID 222AmmoniaHCID 866672826'-Bromo-4-(difluoromethyl)-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazole]-4''(3''H)-thione

Produkt 1

HCID 679795776'-Bromo-4-(difluoromethyl)-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazol]-4''-amineAusbeute 42 %

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

6′-Bromo-4-(difluoromethyl)-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazole]-4″(3″H)-thione (Example 128 Step 3, 0.3 g, 0.73 mmol) was taken up in ammonia (7 M in MeOH) (6.22 mL, 43.6 mmol) and the resulting mixture was heated in the microwave reactor at 110° C. for 30 min. The solvent was evaporated. The same amount of ammonia was added and the mixture was heated and concentrated (5 times). The crude material was dissolved in EtOAc. Aq. citric acid solution (0.1 M) was added and the phases were separated. The citric acid phase was basified with 1 M NaOH and extracted with DCM twice. The combined DCM extracts were concentrated to give the title compound (0.120 g, 42% yield). 20 mg of the product was purified by preparative chromatography to give 11 mg of the title compound: 1H NMR (500 MHz, DMSO-d6) δ ppm 1.19-1.31 (m, 3 H), 1.34-1.48 (m, 3 H), 1.66-1.82 (m, 2 H), 1.90 (d, 1 H), 2.20 (s, 3 H), 2.80-2.95 (m, 2 H), 5.53-5.97 (m, 1 H), 6.53 (s, 2 H), 6.59 (s, 1 H), 7.21 (d, 1 H), 7.33 (d, 1 H); MS (ES+) m/z 396 [M+H]+.

Aufarbeitung

  1. customThe solvent was evaporated
  2. additionThe same amount of ammonia was added
  3. temperaturethe mixture was heated
  4. concentrationconcentrated (5 times)
  5. dissolutionThe crude material was dissolved in EtOAc
  6. additionAq. citric acid solution (0.1 M) was added
  7. customthe phases were separated
  8. extractionextracted with DCM twice
  9. concentrationThe combined DCM extracts were concentrated

Quellen und Nachweise

ORD-Eintrag
ord-41466bbc8d554a05acd67447a17de0ee
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08415483B2

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