N-[(4-methoxyphenyl)methyl]-1,3-thiazol-2-amine → 1-bromo-3-chloro-N-(4-methoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

HRID 1473388ノート

反応式

HRID 1473388 の反応式
[CH3:1][O:2][C:3]1[CH:15]=[CH:14][C:6]([CH2:7][NH:8][C:9]2[S:10][CH:11]=[CH:12][N:13]=2)=[CH:5][CH:4]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Br:26][C:27]1[C:36]2[C:31](=[CH:32][C:33]([S:37](OC3C(F)=C(F)C(F)=C(F)C=3F)(=[O:39])=[O:38])=[CH:34][CH:35]=2)[CH:30]=[C:29]([Cl:52])[N:28]=1>C1COCC1.[Cl-].[NH4+].O>[Br:26][C:27]1[C:36]2[C:31](=[CH:32][C:33]([S:37]([N:8]([CH2:7][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:15][CH:14]=3)[C:9]3[S:10][CH:11]=[CH:12][N:13]=3)(=[O:39])=[O:38])=[CH:34][CH:35]=2)[CH:30]=[C:29]([Cl:52])[N:28]=1

参加物

7

反応物 3

HCID 578640N-[(4-methoxyphenyl)methyl]-1,3-thiazol-2-amineHCID 2733832Lithium HexamethyldisilazideHCID 86687429Perfluorophenyl 1-bromo-3-chloroisoquinoline-6-sulfonate

生成物 1

HCID 866874301-bromo-3-chloro-N-(4-methoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide収率 93.3%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 25517Ammonium Chloride溶媒

実験手順

A round-bottom flask was charged with N-(4-methoxybenzyl)thiazol-2-amine (238 mg, 1.081 mmol) and THF (4912 μl) to give an opaque solution. The flask was cooled in a dry ice-acetone bath for 5 min to give a milky suspension, then lithium bis(trimethylsilyl)amide (1M in THF) (1081 μl, 1.081 mmol) was added. The flask was removed from the bath for 2 min to give a clear solution, then resubmerged. The mixture appeared to remain a solution. After 5 min, a solution of perfluorophenyl 1-bromo-3-chloroisoquinoline-6-sulfonate (480 mg, 0.982 mmol) in THF (3 mL with a 2 mL wash) was added drop wise. After 25 min, the mixture was diluted with saturated aq. ammonium chloride solution and warmed to room temperature. The mixture was diluted with water and extracted with EtOAc. The organic extract was dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (0 to 40% EtOAc/Heptane) to give 1-bromo-3-chloro-N-(4-methoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (481 mg, 0.916 mmol, 93% yield) as a white foam: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm=8.32 (d, J=9.0 Hz, 1H), 8.04 (d, J=1.8 Hz, 1H), 7.83 (dd, J=1.9, 9.0 Hz, 1H), 7.67 (s, 1H), 7.44 (d, J=3.6 Hz, 1H), 7.30 (d, J=8.8 Hz, 2H), 7.07 (d, J=3.5 Hz, 1H), 6.75-6.71 (m, 2H), 5.12 (s, 2H), 3.74 (s, 3H). m/z (ESI) 546.0 (M+H)+.

後処理

  1. customto give an opaque solution
  2. temperatureThe flask was cooled in a dry ice-acetone bath for 5 min
  3. customto give a milky suspension
  4. customThe flask was removed from the bath for 2 min
  5. customto give a clear solution
  6. additionwas added drop wise
  7. waitAfter 25 min
  8. extractionextracted with EtOAc
  9. extractionThe organic extract
  10. dry with materialwas dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was purified by chromatography on silica gel (0 to 40% EtOAc/Heptane)

出典と根拠

ORDレコード
ord-4831468b863846e18a0044a689f9744e
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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