Ammonia → 5'-Bromo-4-methoxy-5''-methyldispiro[cyclohexane-1,2'-[1]-benzofuran-3',2''-imidazol]-4''-amine

HRID 1770960Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1770960
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:16][C:15]3([CH2:21][CH2:20][CH:19]([O:22][CH3:23])[CH2:18][CH2:17]3)[C:8]3([NH:12][C:11](=S)[C:10]([CH3:14])=[N:9]3)[C:6]=2[CH:7]=1.[NH3:24].CO>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:16][C:15]3([CH2:21][CH2:20][CH:19]([O:22][CH3:23])[CH2:18][CH2:17]3)[C:8]3([N:12]=[C:11]([NH2:24])[C:10]([CH3:14])=[N:9]3)[C:6]=2[CH:7]=1

Komponenten

4

Edukt 3

HCID 222Ammonia2×HCID 887Methanol2×HCID 866672755'-Bromo-4-methoxy-5''-methyldispiro[cyclohexane-1,2'-[1]-benzofuran-3',2''-imidazole]-4''(3''H)-thione

Produkt 1

HCID 679795525'-Bromo-4-methoxy-5''-methyldispiro[cyclohexane-1,2'-[1]-benzofuran-3',2''-imidazol]-4''-amineAusbeute 27 %

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A mixture of 5′-bromo-4-methoxy-5″-methyldispiro[cyclohexane-1,2′-[1]benzofuran-3′,2″-imidazole]-4″(3″H)-thione (Example 29 Step 3, 365 mg, 0.92 mmol) and 7M ammonia in MeOH (10 mL, 70.00 mmol) was prepared in a microwave vial. The vial was sealed and the reaction was heated at 120° C. for 30 min in a microwave reactor. The mixture was concentrated and the residue was dissolved in 7M ammonia in McOH (4 mL) and heated once more at 120° C. for 30 min using MW. Again, the mixture was concentrated, 7M ammonia in MeOH (10 mL, 70.00 mmol) was added and the mixture was heated at 120° C. The mixture was concentrated and the crude product was dissolved in 20% MeOH in DCM and filtered through a silica pad and eluted with 20% MeOH in DCM. After concentration of the organic layer, DCM was added to the residue. A solid was formed which was filtered off and washed with DCM, yielding 94 mg of the title compound (27% yield). The mother liquor was concentrated, Et2O was added and the solid was filtered off and dried, yielding a second crop of the title compound (85 mg, 24% yield). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.19 (d, 1H), 1.43 (m, 3H), 1.80 (d, 2H), 1.95 (m, 2H), 2.20 (s, 3H), 3.07 (d, 1H), 3.21 (s, 3H), 6.68 (d, 1H), 6.74 (br. s., 2H), 6.87 (d, 1H), 7.31 (dd, 1H); MS (ES+) m/z 379 [M+H]+.

Aufarbeitung

  1. customwas prepared in a microwave vial
  2. customThe vial was sealed
  3. concentrationThe mixture was concentrated
  4. dissolutionthe residue was dissolved in 7M ammonia in McOH (4 mL)
  5. temperatureheated once more at 120° C. for 30 min
  6. concentrationAgain, the mixture was concentrated
  7. temperaturethe mixture was heated at 120° C
  8. concentrationThe mixture was concentrated
  9. dissolutionthe crude product was dissolved in 20% MeOH in DCM
  10. filtrationfiltered through a silica pad
  11. washeluted with 20% MeOH in DCM
  12. additionAfter concentration of the organic layer, DCM was added to the residue
  13. customA solid was formed which
  14. filtrationwas filtered off
  15. washwashed with DCM

Quellen und Nachweise

ORD-Eintrag
ord-c172c5f9d12c4ca8b4fb89bac79661ec
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09248129B2

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