Ammonia → 6'-Bromo-5-methyl-5'',6''-dihydro-4''H-dispiro[imidazole-2,4'-chromene-2',3''-pyran]-4-amine

HRID 1770965Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1770965
[Br:1][C:2]1[CH:3]=[C:4]2[C:14](=[CH:15][CH:16]=1)[O:13][C:7]1([CH2:12][CH2:11][CH2:10][O:9][CH2:8]1)[CH2:6][C:5]12[NH:20][C:19](=S)[C:18]([CH3:22])=[N:17]1.[NH3:23]>>[Br:1][C:2]1[CH:3]=[C:4]2[C:14](=[CH:15][CH:16]=1)[O:13][C:7]1([CH2:12][CH2:11][CH2:10][O:9][CH2:8]1)[CH2:6][C:5]12[N:20]=[C:19]([NH2:23])[C:18]([CH3:22])=[N:17]1

Komponenten

3

Edukt 2

HCID 222Ammonia2×HCID 866672766'-Bromo-5-methyl-5'',6''-dihydro-4''H-dispiro[imidazole-2,4'-chromene-2',3''-pyran]-4(3H)-thione

Produkt 1

HCID 573861526'-Bromo-5-methyl-5'',6''-dihydro-4''H-dispiro[imidazole-2,4'-chromene-2',3''-pyran]-4-amineAusbeute 43 %

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

6′-Bromo-5-methyl-5″,6″-dihydro-4″H-dispiro[imidazole-2,4′-chromene-2′,3″-pyran]-4(3H)-thione (Example 45 Step 3, 319 mg, 0.84 mmol) was taken up in ammonia (7M in MeOH, 10 mL, 70.00 mmol) and the resulting mixture was heated in the microwave reactor at 120° C. for 2 h. The solvent was evaporated and ammonia (7M in MeOH, 10 mL, 70.00 mmol) was added and the reaction was heated using MW for 1 h at 120° C. The solvent was evaporated and the resulting residue was taken up in DCM and saturated NaHCO3 and poured into a phase separator. The organic phase was dried and concentrated. The crude product was purified by flash chromatography using a gradient of 0-100% EtOAc in heptane followed by a gradient of 0-40% MeOH with 1% NH3 in DCM. The desired fractions were evaporated to give the title compound (130 mg, 43% yield) as a mixture of diastereomers in a 1:1 ratio as determined by NMR: 1H NMR (500 MHz, DMSO-d6) δ ppm 1.41-1.49 (m), 1.76-1.89 (m), 1.89-1.95 (m), 1.95-2.06 (m), 2.21 (s), 2.23 (s), 3.16 (m), 3.41 (d), 3.51 (dd), 3.69 (dd), 3.92 (t), 4.07-4.12 (m), 6.45 (d), 6.47 (d), 6.57 (br. s.), 6.61 (br. s.), 6.82 (d), 7.25 (d), 7.26 (d); MS (ES+) m/z 366.0 [M+H]+.

Aufarbeitung

  1. customThe solvent was evaporated
  2. temperaturethe reaction was heated
  3. customfor 1 h
  4. customat 120° C
  5. customThe solvent was evaporated
  6. additionsaturated NaHCO3 and poured into a phase separator
  7. customThe organic phase was dried
  8. concentrationconcentrated
  9. customThe crude product was purified by flash chromatography
  10. customThe desired fractions were evaporated

Quellen und Nachweise

ORD-Eintrag
ord-c0690581af9b4d9a86850c375fc9facc
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09248129B2

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