Ammonia → 6'-Bromo-4-(difluoromethyl)-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazol]-4''-amine

HRID 1965150

反応式

HRID 1965150 の反応式
[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]=1

参加物

3

反応物 2

HCID 222AmmoniaHCID 866672826'-Bromo-4-(difluoromethyl)-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazole]-4''(3''H)-thione

生成物 1

HCID 679795776'-Bromo-4-(difluoromethyl)-5''-methyl-3'H-dispiro[cyclohexane-1,2'-indene-1',2''-imidazol]-4''-amine収率 42%

反応条件

温度
110 °C

実験手順

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]+.

後処理

  1. customThe solvent was evaporated
  2. additionThe same amount of ammonia was added
  3. temperaturethe mixture was heated
  4. concentrationconcentrated (5 times)
  5. dissolutionThe crude material was dissolved in EtOAc
  6. additionAq. citric acid solution (0.1 M) was added
  7. customthe phases were separated
  8. extractionextracted with DCM twice
  9. concentrationThe combined DCM extracts were concentrated

出典と根拠

ORDレコード
ord-41466bbc8d554a05acd67447a17de0ee
出典データセット
uspto-grants-2013_04
特許番号
US08415483B2

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