Hydrochloric Acid → (S)-1-(5-(5-(pyridin-2-ylthio)-3-(1,3,5-trimethyl-1H-pyrazol-4-yloxy)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)ethane-1,2-diol hydrochloride

HRID 534107ノート

反応式

HRID 534107 の反応式
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[S:7][C:8]1[CH:9]=[C:10]([O:30][C:31]2[C:32]([CH3:38])=[N:33][N:34]([CH3:37])[C:35]=2[CH3:36])[C:11]([NH:14][C:15]2[S:19][N:18]=[C:17]([C@H:20]3[CH2:24][O:23]C4(CCCCC4)[O:21]3)[N:16]=2)=[N:12][CH:13]=1.[ClH:39].C(=O)(O)[O-].[Na+]>C(O)C>[ClH:39].[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[S:7][C:8]1[CH:9]=[C:10]([O:30][C:31]2[C:32]([CH3:38])=[N:33][N:34]([CH3:37])[C:35]=2[CH3:36])[C:11]([NH:14][C:15]2[S:19][N:18]=[C:17]([C@H:20]([OH:21])[CH2:24][OH:23])[N:16]=2)=[N:12][CH:13]=1

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 67487345(S)-N-(5-(pyridin-2-ylthio)-3-(1,3,5-trimethyl-1H-pyrazol-4-yloxy)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decane-2-yl)-1,2,4-thiadiazol-5-amine

生成物 1

HCID 67486348(S)-1-(5-(5-(pyridin-2-ylthio)-3-(1,3,5-trimethyl-1H-pyrazol-4-yloxy)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)ethane-1,2-diol hydrochloride収率 68.8%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

反応条件

温度
75 °C

実験手順

A flask was charged with (S)-N-(5-(pyridin-2-ylthio)-3-(1,3,5-trimethyl-1H-pyrazol-4-yloxy)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decane-2-yl)-1,2,4-thiadiazol-5-amine (1.38 g, 2.40 mmol), ethanol (50 mL), and 3M HCl (1.67 ml, 5.00 mmol) and heated to 75° C. for 1 hour. The reaction was cooled to ambient temperature, and saturated aqueous sodium bicarbonate was added slowly. The mixture was extracted with ethyl acetate and dichloromethane. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified over silica gel (50 to 100% ethyl acetate in hexanes followed 5% methanol in ethyl acetate). The product was dissolved in 10% methanol in dichloromethane and 5 mL 2M HCl in ether was added. The solution was concentrated and dried in a vacuum oven to afford (S)-1-(5-(5-(pyridin-2-ylthio)-3-(1,3,5-trimethyl-1H-pyrazol-4-yloxy)pyridin-2-ylamino)-1,2,4-thiadiazol-3-yl)ethane-1,2-diol hydrochloride (0.958 g, 1.65 mmol, 65.9% yield) as yellow solid. Mass Spectrum (apci) m/z=472.1 (M+H−HCl).

後処理

  1. temperatureThe reaction was cooled to ambient temperature
  2. extractionThe mixture was extracted with ethyl acetate and dichloromethane
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified over silica gel (50 to 100% ethyl acetate in hexanes followed 5% methanol in ethyl acetate)
  7. dissolutionThe product was dissolved in 10% methanol in dichloromethane
  8. addition5 mL 2M HCl in ether was added
  9. concentrationThe solution was concentrated
  10. customdried in a vacuum oven

出典と根拠

ORDレコード
ord-ae602013c9b14f4d87aba5d19830a586
出典データセット
uspto-grants-2014_10
特許番号
US08853409B2

反応ノート

読み込み中…