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Potassium Carbonate → N-tert-Butyl-2-{4-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-piperidin-1-yl}-acetamide

HRID 708254
ノート
印刷プレビュー

反応式

HRID 708254 の反応式
OC(C(F)(F)F)=O.[CH:8]([N:11]1[C:15]([C:16]2[S:17][C:18]3[CH2:19][CH2:20][O:21][C:22]4[CH:29]=[C:28]([CH:30]5[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]5)[CH:27]=[CH:26][C:23]=4[C:24]=3[N:25]=2)=[N:14][CH:13]=[N:12]1)([CH3:10])[CH3:9].C(=O)([O-])[O-].[K+].[K+].[C:42]([NH:46][C:47](=[O:50])[CH2:48]Cl)([CH3:45])([CH3:44])[CH3:43]>C1COCC1.C(Cl)Cl.O>[C:42]([NH:46][C:47](=[O:50])[CH2:48][N:33]1[CH2:34][CH2:35][CH:30]([C:28]2[CH:27]=[CH:26][C:23]3[C:24]4[N:25]=[C:16]([C:15]5[N:11]([CH:8]([CH3:10])[CH3:9])[N:12]=[CH:13][N:14]=5)[S:17][C:18]=4[CH2:19][CH2:20][O:21][C:22]=3[CH:29]=2)[CH2:31][CH2:32]1)([CH3:45])([CH3:44])[CH3:43]
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 3

HCID 11430Potassium CarbonateHCID 222440N-tert-butyl-2-chloroacetamideHCID 866523172-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene TFA salt

生成物 1

HCID 67050586N-tert-Butyl-2-{4-[2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulen-8-yl]-piperidin-1-yl}-acetamide収率 63.4%

試薬・触媒・溶媒 3

HCID 962
Water
溶媒
HCID 6344Dichloromethane溶媒
HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene 375 TFA salt (250 mg, 0.49 mmol) in THF (5 mL) was added potassium carbonate (136 mg, 0.98 mmol) followed by N-tert-butyl-2-chloroacetamide (81 mg, 0.54 mmol). The reaction mixture was stirred for 65 hours before being diluted with DCM and water. The organic layer was dried over anhydrous magnesium sulfate and concentrated in vacuo. The resulting residue was purified by silica gel flash chromatography (SiO2, gradient 0-3% methanol in DCM) then freeze-dried from methanol and water to give 510 as a beige solid (158 mg, 63%). LCMS: RT=3.67 min, [M+H]+=509. 1H NMR δ (ppm) (CDCl3): 8.34 (1H, d, J=8.18 Hz), 7.93 (1H, s), 7.10-7.06 (2H, m), 6.96 (1H, d, J=1.81 Hz), 5.92-5.91 (1H, m), 4.42 (2H, t, J=5.03 Hz), 3.42 (2H, t, J=5.05 Hz), 3.00-2.91 (4H, m), 2.61-2.48 (1H, m), 2.35-2.24 (2H, m), 1.96-1.87 (3H, m), 1.83-1.71 (1H, m), 1.64 (6H, d, J=6.63 Hz), 1.39 (9H, s)

後処理

  1. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  2. concentrationconcentrated in vacuo
  3. customThe resulting residue was purified by silica gel flash chromatography (SiO2, gradient 0-3% methanol in DCM)
  4. dry with materialthen freeze-dried from methanol and water

出典と根拠

ORDレコード
ord-e91d8e5673ec470193b32e1da7638add
出典データセット
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09175009B2

反応ノート

読み込み中…

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