Hydrochloric Acid → 3-[2-amino-6-(5-chloro-1H,3H-benzo[de]isochromen-6-yl)-pyrimidin-4-ylsulfanyl]-propan-1-ol

HRID 217303

反応式

HRID 217303 の反応式
[Cl:1][C:2]1[C:3]([C:15]2[CH:20]=[C:19]([S:21]([CH3:23])=O)[N:18]=[C:17]([NH2:24])[N:16]=2)=[C:4]2[CH:13]=[CH:12][CH:11]=[C:10]3[C:5]2=[C:6]([CH:14]=1)[CH2:7][O:8][CH2:9]3.SC[CH2:27][CH2:28][OH:29].C(N(CC)C(C)C)(C)C.Cl>CN(C)C=O.O>[NH2:24][C:17]1[N:18]=[C:19]([S:21][CH2:23][CH2:27][CH2:28][OH:29])[CH:20]=[C:15]([C:3]2[C:2]([Cl:1])=[CH:14][C:6]3[CH2:7][O:8][CH2:9][C:10]4[C:5]=3[C:4]=2[CH:13]=[CH:12][CH:11]=4)[N:16]=1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 81531Diisopropylethylamine2 回HCID 882113-Mercaptopropanol2 回HCID 578987824-(5-chloro-1H,3H-benzo[de]isochromen-6-yl)-6-methanesulfinyl-pyrimidin-2-ylamine

生成物 1

HCID 578988233-[2-amino-6-(5-chloro-1H,3H-benzo[de]isochromen-6-yl)-pyrimidin-4-ylsulfanyl]-propan-1-ol収率 42.7%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

Partially purified 4-(5-chloro-1H,3H-benzo[de]isochromen-6-yl)-6-methanesulfinyl-pyrimidin-2-ylamine (29.1 mg) obtained in Step 5 of Example 314 was dissolved in N,N-dimethylformamide (1 mL), 3-mercapto-1-propanol (17 μL, 0.197 mmol) and N,N-diisopropylethylamine (55 μL, 0.316 mmol) were added, and this was stirred at 80° C. Four hours later, 3-mercapto-1-propanol (8 μL, 0.093 mmol) and N,N-diisopropylethylamine (23 μL, 0.132 mmol) were added, and this was stirred at 80° C. for another eleven hours. The reaction solution was cooled to room temperature, water (10 mL) and 1 N hydrochloric acid (1 mL) were added, and this was extracted with ethyl acetate (15 mL, 10 mL). The organic layers were combined, and then washed with 0.01 N hydrochloric acid (8 mL), water (8 mL), and brine (8 mL), then dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The obtained residue was purified by silica gel thin layer chromatography (developing solvent; methylene chloride:methanol=20:1), and thus, 3-[2-amino-6-(5-chloro-1H,3H-benzo[de]isochromen-6-yl)-pyrimidin-4-ylsulfanyl]-propan-1-ol (compound 326) (13.4 mg) was obtained.

後処理

  1. stirringthis was stirred at 80° C. for another eleven hours
  2. temperatureThe reaction solution was cooled to room temperature
  3. extractionthis was extracted with ethyl acetate (15 mL, 10 mL)
  4. washwashed with 0.01 N hydrochloric acid (8 mL), water (8 mL), and brine (8 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained residue was purified by silica gel thin layer chromatography (developing solvent; methylene chloride:methanol=20:1)

出典と根拠

ORDレコード
ord-04d1d372b1e24831a3fa26eeca3bcd87
出典データセット
uspto-grants-2012_06
特許番号
US08193351B2

関連ノート

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