1,4-Dioxane → 6-(Benzylthio)-1-(4-chloro-2-methoxyphenyl)isoquinoline

HRID 1473377노트

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HRID 1473377 반응식
[CH2:1]([S:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15](Cl)=[N:14][CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:20][C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[C:23]([O:30][CH3:31])[CH:22]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>CCOC(C)=O.CCCCCCC.O>[CH2:1]([S:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15]([C:24]1[CH:25]=[CH:26][C:21]([Cl:20])=[CH:22][C:23]=1[O:30][CH3:31])=[N:14][CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

7

반응물 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 3858606(4-Chloro-2-methoxyphenyl)boronic acidHCID 866874176-(Benzylthio)-1-chloroisoquinoline

생성물 1

HCID 866874206-(Benzylthio)-1-(4-chloro-2-methoxyphenyl)isoquinoline수율 74.6%

시약·촉매·용매 2

HCID 962Water용매HCID 21899848Ethylacetate heptane용매

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온도
100 °C

실험 절차

A round-bottom flask was charged with 6-(benzylthio)-1-chloroisoquinoline (from STEP 1 of INTERMEDIATE LLL) (688.23 mg, 2.408 mmol), (4-chloro-2-methoxyphenyl)boronic acid (494 mg, 2.65 mmol), Pd(AmPhos)2Cl2 (85 mg, 0.120 mmol), potassium phosphate (1534 mg, 7.22 mmol), dioxane (6020 μl), and water (2007 μl). The vial was flushed with Ar (g), then 1,4-dioxane (6020 μl) and water (2007 μl) were added. The vial was sealed and heated in a Biotage Initiator microwave reactor for 30 min at 100° C. The mixture was cooled to room temperature, then diluted with water and extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The crude product was purified by chromatography on silica gel (40-g, 10 to 40%, then 40-70% EtOAc/Heptane, 25-g silica gel loading column) to give 6-(benzylthio)-1-(4-chloro-2-methoxyphenyl)isoquinoline (704.36 mg, 1.797 mmol, 74.6% yield) as a light-yellow foam: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm=8.56 (d, J=5.8 Hz, 1H), 7.65 (d, J=1.9 Hz, 1H), 7.55-7.48 (m, 2H), 7.44-7.39 (m, 2H), 7.38-7.27 (m, 5H), 7.11 (dd, J=1.9, 8.1 Hz, 1H), 7.04 (d, J=1.9 Hz, 1H), 4.30 (s, 2H), 3.70 (s, 3H); m/z (ESI) 392.2 (M+H)+.

후처리

  1. customThe vial was flushed with Ar (g)
  2. addition1,4-dioxane (6020 μl) and water (2007 μl) were added
  3. customThe vial was sealed
  4. temperatureThe mixture was cooled to room temperature
  5. additiondiluted with water
  6. extractionextracted with EtOAc (2×)
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by chromatography on silica gel (40-g, 10 to 40%

출처 및 근거

ORD 기록
ord-ba03fca48cbd42718245990a7398c214
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09012443B2

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