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

HRID 217303

반응식

HRID 217303 반응식
[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

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 81531Diisopropylethylamine2회HCID 882113-Mercaptopropanol2회HCID 578987824-(5-chloro-1H,3H-benzo[de]isochromen-6-yl)-6-methanesulfinyl-pyrimidin-2-ylamine

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

반응 조건

온도
80 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-04d1d372b1e24831a3fa26eeca3bcd87
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08193351B2

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