Potassium bis(trimethylsilyl)amide → 2-{[2-(Benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acid

HRID 577523ノート

反応式

HRID 577523 の反応式
[Cl:1][C:2]1[C:11]2[C:10](=[O:12])[NH:9][CH2:8][CH2:7][C:6]=2[C:5]([C:13]([O:15]C)=[O:14])=[CH:4][C:3]=1[O:17][CH:18]([CH3:20])[CH3:19].[CH2:21]([O:28][C:29]1[C:34]([CH2:35]Cl)=[C:33]([CH3:37])[CH:32]=[C:31]([CH3:38])[N:30]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+]>O1CCOCC1>[CH2:21]([O:28][C:29]1[C:34]([CH2:35][N:9]2[CH2:8][CH2:7][C:6]3[C:5]([C:13]([OH:15])=[O:14])=[CH:4][C:3]([O:17][CH:18]([CH3:20])[CH3:19])=[C:2]([Cl:1])[C:11]=3[C:10]2=[O:12])=[C:33]([CH3:37])[CH:32]=[C:31]([CH3:38])[N:30]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

参加物

5

反応物 3

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 612578682-(Benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridineHCID 86723680Methyl 8-chloro-1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinoline-5-carboxylate

生成物 1

HCID 867237502-{[2-(Benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acid収率 33%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

To a mixture of methyl 8-chloro-1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinoline-5-carboxylate (Cpd F, 92.0 mg, 0.310 mmol) and 2-(benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridine (Cpd Z, 97.1 mg, 0.371 mmol) in 1,4-dioxane (3 mL) was added KHMDS (308 mg, 1.54 mmol). The reaction mixture was heated at 100° C. for 1 hour. The solvent was removed under vacuum and the residue diluted with EtOAc (10 mL) and water (10 mL). The pH of the aqueous layer was adjusted to 3-4 using 1N HCl. The aqueous layer was extracted with EtOAc (25 mL) and the organic layer concentrated under vacuum. The residue was purified by column chromatography (silica gel, heptanes/EtOAc) to give 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-8-chloro-1-oxo-7-(propan-2-yloxy)-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acid (90a, 52 mg, 33% yield) as an oil.

後処理

  1. customThe solvent was removed under vacuum
  2. additionthe residue diluted with EtOAc (10 mL) and water (10 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (25 mL)
  4. concentrationthe organic layer concentrated under vacuum
  5. customThe residue was purified by column chromatography (silica gel, heptanes/EtOAc)

出典と根拠

ORDレコード
ord-2b0f8efae24d49a9be6d2a37161b56b2
出典データセット
uspto-grants-2015_05
特許番号
US09040515B2

反応ノート

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