Ammonia → US9000184, 5, isomer 1

HRID 1468238노트

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HRID 1468238 반응식
[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

참가 물질

3

반응물 2

HCID 222Ammonia2회HCID 867067107'-Bromo-4-methoxy-5''-methyl-3',4'-dihydrodispiro[cyclohexane-1,2'-naphthalene-1',2''-imidazole]-4''(3''H)-thione2회

생성물 1

HCID 72714746US9000184, 5, isomer 1

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온도
120 °C

실험 절차

(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:

후처리

  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

출처 및 근거

ORD 기록
ord-e38b6d7e6d1446f5813576a885f6d1b2
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09000184B2

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