N-[(4-methoxyphenyl)methyl]-1,3-thiazol-2-amine → 4-chloro-N,2-bis(4-methoxybenzyl)-1-oxo-N-(thiazol-2-yl)-1,2-dihydroisoquinoline-7-sulfonamide

HRID 1473700ノート

反応式

HRID 1473700 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.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Cl:26][C:27]1[C:36]2[C:31](=[CH:32][C:33]([S:37](Cl)(=[O:39])=[O:38])=[CH:34][CH:35]=2)[C:30](=[O:41])[N:29]([CH2:42][C:43]2[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[CH:45][CH:44]=2)[CH:28]=1>C1COCC1>[Cl: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)[C:30](=[O:41])[N:29]([CH2:42][C:43]2[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[CH:45][CH:44]=2)[CH:28]=1

参加物

5

反応物 3

HCID 578640N-[(4-methoxyphenyl)methyl]-1,3-thiazol-2-amineHCID 2733832Lithium HexamethyldisilazideHCID 866877844-Chloro-2-(4-methoxybenzyl)-1-oxo-1,2-dihydroisoquinoline-7-sulfonyl chloride

生成物 1

HCID 866877854-chloro-N,2-bis(4-methoxybenzyl)-1-oxo-N-(thiazol-2-yl)-1,2-dihydroisoquinoline-7-sulfonamide収率 48.9%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

A round-bottom flask was charged with N-(4-methoxybenzyl)thiazol-2-amine (0.213 g, 0.967 mmol) and THF (4.40 mL), and the vessel was cooled to −78° C. for 15 minutes. LHMDS (1.0 M in THF) (1.055 mL, 1.055 mmol) was then added drop wise over 1 minute. The reaction was stirred for 10 minutes, and then a solution of 4-chloro-2-(4-methoxybenzyl)-1-oxo-1,2-dihydroisoquinoline-7-sulfonyl chloride (0.350 g, 0.879 mmol) in THF (1.60 mL) was added drop wise. The bath was removed, and the resulting mixture was stirred for 45 minutes, until complete conversion to 4-chloro-N,2-bis(4-methoxybenzyl)-1-oxo-N-(thiazol-2-yl)-1,2-dihydroisoquinoline-7-sulfonamide. The reaction was diluted with saturated ammonium chloride (aq.) solution (30 mL), and was washed with ethyl acetate (20 mL×3). The organic layers were combined, dried over magnesium sulfate, filtered and concentrated. The resulting material was purified via silica gel chromatography (ISCO, 40 g), eluting with 0 to 100% ethyl acetate in heptanes to provide 0.250 g of 4-chloro-N,2-bis(4-methoxybenzyl)-1-oxo-N-(thiazol-2-yl)-1,2-dihydroisoquinoline-7-sulfonamide. m/z (ESI) 583.2 (M+H)+.

後処理

  1. customThe bath was removed
  2. stirringthe resulting mixture was stirred for 45 minutes, until complete conversion to 4-chloro-N,2-bis(4-methoxybenzyl)-1-oxo-N-(thiazol-2-yl)-1,2-dihydroisoquinoline-7-sulfonamide
  3. additionThe reaction was diluted with saturated ammonium chloride (aq.) solution (30 mL)
  4. washwas washed with ethyl acetate (20 mL×3)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting material was purified via silica gel chromatography (ISCO, 40 g)
  9. washeluting with 0 to 100% ethyl acetate in heptanes

出典と根拠

ORDレコード
ord-657a6808c9a84aea804fe04a05c65847
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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