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

HRID 1473377ノート

反応式

HRID 1473377 の反応式
[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

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 21899848Ethylacetate heptane溶媒

反応条件

温度
100 °C

実験手順

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)+.

後処理

  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%

出典と根拠

ORDレコード
ord-ba03fca48cbd42718245990a7398c214
出典データセット
uspto-grants-2015_04
特許番号
US09012443B2

反応ノート

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