Ammonia → US9000184, 5, isomer 1

HRID 1468238Notes

Reaction equation

HRID 1468238 reaction equation
[Br:1][C:2]1[CH:24]=[C:23]2[C:5]([CH2:6][CH2:7][C:8]3([C:16]42[NH:20][C:19](=S)[C:18]([CH3:22])=[N:17]4)[CH2:13][CH2:12][CH:11]([O:14][CH3:15])[CH2:10][CH2:9]3)=[CH:4][CH:3]=1.[NH3:25]>>[Br:1][C:2]1[CH:24]=[C:23]2[C:5]([CH2:6][CH2:7][C:8]3([C:16]42[N:20]=[C:19]([NH2:25])[C:18]([CH3:22])=[N:17]4)[CH2:13][CH2:12][CH:11]([O:14][CH3:15])[CH2:10][CH2:9]3)=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 222Ammonia2×HCID 867067107'-Bromo-4-methoxy-5''-methyl-3',4'-dihydrodispiro[cyclohexane-1,2'-naphthalene-1',2''-imidazole]-4''(3''H)-thione2×

Product 1

HCID 72714746US9000184, 5, isomer 1

Conditions

Temperature
120 °C

Procedure

(7′-Bromo-4-methoxy-5″-methyl-3′,4′-dihydrodispiro[cyclohexane-1,2′-naphthalene-1′,2″-imidazole]-4″(3″H)-thione (Intermediate 15, 0.191 g, 0.47 mmol) and ammonia (7M in MeOH, 2.5 mL, 17.5 mmol) were mixed 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 ammonia (7M in MeOH, 2.5 mL, 17.5 mmol) and heated at 120° C. for 30 min in a microwave reactor. This was repeated six more times (8 runs in total). After evaporation of the solvent, the residue was partitioned between DCM and 2 M citric acid. The phases were separated and the organic layer was extracted with 2 M citric acid. The organic layer was discarded while the combined aqueous phases were basified to ˜pH 12 by addition of 50% aq. NaOH. The aqueous phase was then extracted with EtOAc three times. The combined organic layers were dried using a phase separator and concentrated. The product was purified by preparative HPLC to give two isomers:

Workup

  1. customThe vial was sealed
  2. concentrationThe mixture was concentrated
  3. temperatureheated at 120° C. for 30 min in a microwave reactor
  4. customAfter evaporation of the solvent
  5. customthe residue was partitioned between DCM and 2 M citric acid
  6. customThe phases were separated
  7. extractionthe organic layer was extracted with 2 M citric acid
  8. additionby addition of 50% aq. NaOH
  9. extractionThe aqueous phase was then extracted with EtOAc three times
  10. customThe combined organic layers were dried
  11. concentrationconcentrated
  12. customThe product was purified by preparative HPLC
  13. customto give two isomers

Sources & evidence

ORD record
ord-e38b6d7e6d1446f5813576a885f6d1b2
Source dataset
uspto-grants-2015_04
Patent number
US09000184B2

Reaction notes

Loading…