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Sodium bis(trimethylsilyl)amide → Tert-butyl 4-((1r)-1-(6-(5-fluoro-6-methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2h-pyran-2-yl)-9h-purin-6-yl)pyridin-3-yl)ethyl)piperazine-1-carboxylate

HRID 1812268
ノート
印刷プレビュー

反応式

HRID 1812268 の反応式
F[C:2]1[N:7]=[CH:6][C:5]([C@H:8]([N:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)[CH3:9])=[CH:4][C:3]=1[C:23]1[N:31]=[C:30]([CH3:32])[N:29]=[C:28]2[C:24]=1[N:25]=[CH:26][N:27]2[CH:33]1[CH2:38][CH2:37][CH2:36][CH2:35][O:34]1.[F:39][C:40]1[CH:41]=[C:42]([NH2:48])[CH:43]=[N:44][C:45]=1[O:46][CH3:47].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[F:39][C:40]1[CH:41]=[C:42]([NH:48][C:2]2[N:7]=[CH:6][C:5]([C@H:8]([N:10]3[CH2:11][CH2:12][N:13]([C:16]([O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:17])[CH2:14][CH2:15]3)[CH3:9])=[CH:4][C:3]=2[C:23]2[N:31]=[C:30]([CH3:32])[N:29]=[C:28]3[C:24]=2[N:25]=[CH:26][N:27]3[CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][O:34]2)[CH:43]=[N:44][C:45]=1[O:46][CH3:47]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 454803515-Fluoro-6-methoxypyridin-3-amineHCID 68518749tert-butyl 4-((1R)-1-(6-fluoro-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-3-yl)ethyl)piperazine-1-carboxylate

生成物 1

HCID 68515999Tert-butyl 4-((1r)-1-(6-(5-fluoro-6-methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2h-pyran-2-yl)-9h-purin-6-yl)pyridin-3-yl)ethyl)piperazine-1-carboxylate収率 55.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-20 °C

実験手順

A mixture of tert-butyl 4-((1R)-1-(6-fluoro-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-3-yl)ethyl)piperazine-1-carboxylate (0.673 g, 1.280 mmol) in THF (15 mL) under inert atmosphere was treated with a solution of 5-fluoro-6-methoxypyridin-3-amine (0.364 g, 2.56 mmol) in THF (10 mL) via syringe. The mixture was chilled to −20° C. in a diluted dry ice/acetone bath, then sodium bis(trimethylsilyl)amide (1.0 M in THF, Aldrich; 3.84 mL, 3.84 mmol) was added slowly via syringe into the reaction mixture. After the addition, the ice bath was removed and the mixture was allowed to stir under inert atmosphere for 1 h. The mixture was diluted with chloroform (20 mL) and water (10 mL). The organic layer was extracted with chloroform (3×10 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was adsorbed onto a plug of silica gel and purified by chromatography through a silica-gel column (80 g) eluting with 100% ethyl acetate to give tert-butyl 4-((1R)-1-(6-(5-fluoro-6-methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-3-yl)ethyl)piperazine-1-carboxylate (0.459 g, 0.709 mmol, 55.3% yield) as a tan solid. 1H NMR (400 MHz, CDCl3) δ 12.61 (s, 1H) 9.65 (t, J=1.96 Hz, 1H) 8.31 (dd, J=12.52, 2.35 Hz, 1H) 8.18-8.23 (m, 2H) 8.03 (d, J=2.35 Hz, 1H) 5.80 (dd, J=10.47, 2.05 Hz, 1H) 3.96 (s, 3H) 3.76 (s, 1H) 3.55 (d, J=6.85 Hz, 1H) 3.36 (s, 4H) 2.85 (s, 3H) 2.40 (d, J=3.33 Hz, 4H) 2.07 (s, 1H) 2.02 (s, 1H) 1.97 (s, 1H) 1.54-1.81 (m, 2H) 1.41 (d, J=6.65 Hz, 3H) 1.36 (s, 9H) 1.19 (s, 1H) 0.90 (d, J=6.65 Hz, 1H). m/z (ESI, +ve ion) 648.2 (M+H)+.

後処理

  1. additionAfter the addition
  2. customthe ice bath was removed
  3. additionThe mixture was diluted with chloroform (20 mL) and water (10 mL)
  4. extractionThe organic layer was extracted with chloroform (3×10 mL)
  5. dry with materialThe combined organic extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. custompurified by chromatography through a silica-gel column (80 g)
  9. washeluting with 100% ethyl acetate

出典と根拠

ORDレコード
ord-8e8a4c10cd314deb8187b57cd0de05fb
出典データセット
uspto-grants-2013_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08362241B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート