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Sodium Carbonate → (3R)-tert-butyl 3-(6-(5-(6-cyclopropylpyrazin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)piperidine-1-carboxylate

HRID 1529275
ノート
印刷プレビュー

反応式

HRID 1529275 の反応式
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[C:15]2[C:10](=[CH:11][C:12](B3OC(C)(C)C(C)(C)O3)=[CH:13][CH:14]=2)[C:9]([C:25]2[N:30]=[C:29]([O:31][C@@H:32]3[CH2:37][CH2:36][CH2:35][N:34]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:33]3)[CH:28]=[N:27][CH:26]=2)=[N:8]1.Br[C:46]1[CH:51]=[N:50][CH:49]=[C:48]([CH:52]2[CH2:54][CH2:53]2)[N:47]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:52]1([C:48]2[N:47]=[C:46]([C:12]3[CH:11]=[C:10]4[C:15](=[CH:14][CH:13]=3)[N:7]([CH:2]3[CH2:3][CH2:4][CH2:5][CH2:6][O:1]3)[N:8]=[C:9]4[C:25]3[N:30]=[C:29]([O:31][C@@H:32]4[CH2:37][CH2:36][CH2:35][N:34]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:33]4)[CH:28]=[N:27][CH:26]=3)[CH:51]=[N:50][CH:49]=2)[CH2:54][CH2:53]1
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

6

反応物 3

HCID 10340Sodium CarbonateHCID 457883052-Bromo-6-cyclopropylpyrazineHCID 86709761(3R)-tert-butyl 3-(6-(1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)piperidine-1-carboxylate

生成物 1

HCID 67959666(3R)-tert-butyl 3-(6-(5-(6-cyclopropylpyrazin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)piperidine-1-carboxylate収率 70%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A glass microwave reaction vessel was charged with (3R)-tert-butyl 3-(6-(1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)piperidine-1-carboxylate (1.315 g, 2.17 mmol) and Pd(PPh3)4 (0.125 g, 0.11 mmol). The tube was sealed and evacuated under vacuum and back-filled with N2 (g). A solution of 2-bromo-6-cyclopropylpyrazine (0.562 g, 2.82 mmol) in dioxane (1.8 mL) and 2 M Na2CO3 (5.43 mL, 10.86 mmol) were added. The reaction mixture was stirred and heated at 100° C. for 2 h. After cooling to RT, the organic layer was separated and dried over anhydrous Na2SO4, filtered and concentrated. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (80 g), eluting with a gradient of 0% to 40% EtOAc in hexanes, to provide (3R)-tert-butyl 3-(6-(5-(6-cyclopropylpyrazin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)piperidine-1-carboxylate (0.910 g, 1.52 mmol, 70% yield) as a yellow foam. MS (ESI, pos. ion) m/z: 598.2 (M+1).

後処理

  1. customA glass microwave reaction vessel
  2. customThe tube was sealed
  3. customevacuated under vacuum
  4. additionback-filled with N2 (g)
  5. temperatureAfter cooling to RT
  6. customthe organic layer was separated
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude material was absorbed onto a plug of silica gel
  11. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (80 g)
  12. washeluting with a gradient of 0% to 40% EtOAc in hexanes

出典と根拠

ORDレコード
ord-21bf32ab9a914098b7e6c9d454a92910
出典データセット
uspto-grants-2015_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09090593B2

反応ノート

読み込み中…

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