Hydrochloric Acid → 3-((9H-Purin-6-ylthio)methyl)-8-methyl-2-o-tolylquinoline

HRID 216760

반응식

HRID 216760 반응식
C(Br)(Br)(Br)Br.[CH3:6][C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:16]=1[N:15]=[C:14]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH3:23])[C:13]([CH2:24]O)=[CH:12]2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH-].[Na+].BrCC1C(C2C=CC=CC=2C)=NC2C(C=1)=CC=CC=2C.O.[SH:68][C:69]1[N:77]=[CH:76][N:75]=[C:74]2[C:70]=1[NH:71][CH:72]=[N:73]2.Cl>C(Cl)Cl.C1COCC1.[Cl-].[Na+].O>[N:77]1[C:69]([S:68][CH2:24][C:13]2[C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[CH3:23])=[N:15][C:16]3[C:11]([CH:12]=2)=[CH:10][CH:9]=[CH:8][C:7]=3[CH3:6])=[C:70]2[C:74]([NH:73][CH:72]=[N:71]2)=[N:75][CH:76]=1

참가 물질

11

반응물 7

HCID 313Hydrochloric AcidHCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 57707986(8-Methyl-2-o-tolylquinolin-3-yl)methanolHCID 577080653-(Bromomethyl)-8-methyl-2-(2-methylphenyl)quinolineHCID 178527204HCID 178527204, 화합물

생성물 1

HCID 1784241993-((9H-Purin-6-ylthio)methyl)-8-methyl-2-o-tolylquinoline

시약·촉매·용매 3

HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매HCID 57417360Sodium chloride; water용매

반응 조건

온도
0 °C

실험 절차

Solid carbontetrabromide (429 mg, 1.29 mmol) was added to a mixture of (8-methyl-2-o-tolylquinolin-3-yl)methanol (227 mg, 0.86 mmol) and triphenylphosphine (339 mg, 1.29 mmol) in CH2Cl2 (5 mL) at 0° C., and the mixture was stirred at 0° C. for 0.5 h. The crude mixture was concentrated under reduced pressure, evaporated onto silica gel, and purified by flash chromatography (Biotage® Si 25+M) eluting with EtOAc/hexane (0% to 10%) to provide an off-white solid; used without further purification, MS (ESI+) m/z=326.0 (M). A 2.0M aqueous solution of sodium hydroxide (0.86 mL, 1.72 mmol) was added to a mixture of 3-(bromomethyl)-8-methyl-2-o-tolylquinoline (140 mg, 0.43 mmol) and 6-mercaptopurine monohydrate (146 mg, 0.86 mmol) in THF (1.6 mL), and the biphasic mixture was heated under reflux for 5 h. The reaction mixture was cooled to 0° C., neutralized by the addition of 1N aqueous HCl, diluted with brine (10 mL), and extracted with THF (3×15 mL). The combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The resulting yellow solid was dissolved in THF/DMSO, evaporated onto silica gel, and purified by flash chromatography (Biotage® Si 25+M) eluting with acetone/hexane (20% to 50%). The resulting off-white solid was recrystallized from THF/MeOH to provide a white solid [PI3δ IC50=889 nM]. MS (ESI+) m/z=398.1 (M+1).

후처리

  1. concentrationThe crude mixture was concentrated under reduced pressure
  2. customevaporated onto silica gel
  3. custompurified by flash chromatography (Biotage® Si 25+M)
  4. washeluting with EtOAc/hexane (0% to 10%)
  5. customto provide an off-white solid
  6. customused without further purification, MS (ESI+) m/z=326.0 (M)
  7. temperaturethe biphasic mixture was heated
  8. temperatureunder reflux for 5 h
  9. temperatureThe reaction mixture was cooled to 0° C.
  10. extractionextracted with THF (3×15 mL)
  11. dry with materialThe combined organic layers were dried (MgSO4)
  12. concentrationconcentrated under reduced pressure
  13. dissolutionThe resulting yellow solid was dissolved in THF/DMSO
  14. customevaporated onto silica gel
  15. custompurified by flash chromatography (Biotage® Si 25+M)
  16. washeluting with acetone/hexane (20% to 50%)
  17. customThe resulting off-white solid was recrystallized from THF/MeOH
  18. customto provide a white solid [PI3δ IC50=889 nM]

출처 및 근거

ORD 기록
ord-a7b224a9d4854de6867ce8a8e31ea2ee
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08193199B2

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