반응식
[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]=1참가 물질
반응 조건
- 온도
- 110 °C
실험 절차
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]+.
후처리
- customThe solvent was evaporated
- additionThe same amount of ammonia was added
- temperaturethe mixture was heated
- concentrationconcentrated (5 times)
- dissolutionThe crude material was dissolved in EtOAc
- additionAq. citric acid solution (0.1 M) was added
- customthe phases were separated
- extractionextracted with DCM twice
- concentrationThe combined DCM extracts were concentrated
출처 및 근거
- ORD 기록
- ord-22a742acc5f3414a88829f22f9764227
- 출처 데이터셋
- uspto-grants-2014_10
- 특허 번호
- US08865911B2
연결된 노트
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