Hydrochloric Acid → 4-(4-(2-(Methylthio)-6-oxo-1,6-dihydropyrimidin-5-yl)pyrimidin-2-ylamino)benzonitrile

HRID 2359773ノート

反応式

HRID 2359773 の反応式
[C:1]([C:4]1[C:5](=[O:12])[NH:6][C:7]([S:10][CH3:11])=[N:8][CH:9]=1)(=O)[CH3:2].[C:13](OC(N(C)C)N(C)C)(C)(C)C.[C:25]([C:27]1[CH:32]=[CH:31][C:30]([NH:33][C:34]([NH2:36])=[NH:35])=[CH:29][CH:28]=1)#[N:26].C([O-])([O-])=O.[K+].[K+].Cl>>[CH3:11][S:10][C:7]1[NH:6][C:5](=[O:12])[C:4]([C:1]2[CH:2]=[CH:13][N:36]=[C:34]([NH:33][C:30]3[CH:29]=[CH:28][C:27]([C:25]#[N:26])=[CH:32][CH:31]=3)[N:35]=2)=[CH:9][N:8]=1

参加物

6

反応物 5

HCID 313Hydrochloric Acid2 回HCID 11430Potassium Carbonate2 回HCID 79885tert-Butoxy bis(dimethylamino)methaneHCID 566989835-acetyl-2-(methylthio)pyrimidin-4(3H)-oneHCID 178510065HCID 178510065、化合物2 回

生成物 1

HCID 679833184-(4-(2-(Methylthio)-6-oxo-1,6-dihydropyrimidin-5-yl)pyrimidin-2-ylamino)benzonitrile収率 47%

反応条件

温度
120 °C

実験手順

5-Acetyl-2-(methylthio)pyrimidin-4(3H)-one (33) (1.094 g, 5.94 mmol) was dissolved in 1-tert-butoxy-N,N,N′,N′-tetramethylmethanediamine (12.26 mL, 59.4 mmol), then the reaction mixture was heated at 120° C. for 6 hours. The reaction mixture was concentrated in vacuo, and dried over high vacuum for 1 hour. The crude intermediate was taken up in DMF (31.6 mL), then 1-(4-cyanophenyl)guanidine (2.076 g, 8.91 mmol) and K2CO3 (4.10 g, 29.7 mmol) were added. The reaction mixture was heated at 120° C. for 48 hours. Additional 1-(4-cyanophenyl)guanidine (2.076 g, 8.91 mmol) and K2CO3 (3.69 g, 26.7 mmol) were added, and the reaction mixture was stirred at 120° C. for additional 18 hours. The reaction mixture was cooled to rt, then was slowly poured into an ice-cooled 1N HCl solution while stirring vigorously. The reaction mixture was neutralized with additional 1N HCl, then the reaction mixture was allowed to stir for an additional 30 minutes. The resulting precipitate was filtered, washed multiple times with DI water, 2-propanol, then diethyl ether. The resulting crude product was dried over high vacuum for 18 hours to obtain the desired product as a red/brown solid (940 mg, 47% yield). MS (ES+): m/z=337.2 (100) [MH+]. HPLC: tR=1.35 minutes over 3 minutes. Purity: 72% [HPLC (LC/MS) at 220 nm].

後処理

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customdried over high vacuum for 1 hour
  3. temperatureThe reaction mixture was heated at 120° C. for 48 hours
  4. temperatureThe reaction mixture was cooled to rt
  5. stirringwhile stirring vigorously
  6. stirringto stir for an additional 30 minutes
  7. filtrationThe resulting precipitate was filtered
  8. washwashed multiple times with DI water, 2-propanol
  9. dry with materialThe resulting crude product was dried over high vacuum for 18 hours

出典と根拠

ORDレコード
ord-1b586c6ad0634b5781809d6ac037c9ff
出典データセット
uspto-grants-2014_04
特許番号
US08685993B2

反応ノート

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