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Sodium Carbonate → tert-butyl 3-(4-amino-3-{4-[(5,7-dimethyl-1,3-benzoxazol-2-yl)amino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-piperidinecarboxylate

HRID 897897
ノート
印刷プレビュー

反応式

HRID 897897 の反応式
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]3[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]3)[N:9]=[C:10](I)[C:3]=12.[CH3:25][C:26]1[CH:27]=[C:28]([CH3:51])[C:29]2[O:33][C:32]([NH:34][C:35]3[CH:40]=[CH:39][C:38](B4OC(C)(C)C(C)(C)O4)=[CH:37][CH:36]=3)=[N:31][C:30]=2[CH:50]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.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>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]3[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]3)[N:9]=[C:10]([C:38]3[CH:37]=[CH:36][C:35]([NH:34][C:32]4[O:33][C:29]5[C:28]([CH3:51])=[CH:27][C:26]([CH3:25])=[CH:50][C:30]=5[N:31]=4)=[CH:40][CH:39]=3)[C:3]=12
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

7

反応物 3

HCID 10340Sodium CarbonateHCID 11581347(5,7-Dimethyl-benzoxazol-2-yl)-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-amine2 回HCID 22346738tert-butyl (3R)-3-{4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl}piperidine-1-carboxylate

生成物 1

HCID 22346853tert-butyl 3-(4-amino-3-{4-[(5,7-dimethyl-1,3-benzoxazol-2-yl)amino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-piperidinecarboxylate収率 37.8%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒2 回HCID 962Water溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
80 °C

実験手順

The mixture of tert-butyl 3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-piperidinecarboxylate (0.6 g, 0.00135 mol), N-(5,7-dimethyl-1,3-benzoxazol-2-yl)-N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]amine (0.59 g, 0.00162 mol), tetrakis(triphenylphosphine)palladium (0.078 g, 0.000068 mol) and sodium carbonate (0.36 g, 0.00338 mol) in ethylene glycol dimethyl ether (50 mL) and water (10 mL) was heated at 80° C. for 16 hours under an atmosphere of nitrogen. After cooled the mixture to the room temperature, more N-(5,7-dimethyl-1,3-benzoxazol-2-yl)-N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]amine (0.24 g, 0.00066 mol), tetrakis(triphenylphosphine)palladium (0.078 g, 0.000068 mol) were added, and the mixture was stirred at 80° C. for 5 hours. The mixture was allowed to cool to ambient temperature, and the solvent was removed under the reduced pressure. The residue was partitioned between water and dichloromethane. The aqueous layer was extracted with dichloromethane (3×50 mL). The combined organic extracts were washed with water, saturated aqueous sodium bicarbonate solution, and brine, and dried over magnesium sulfate. The solvents were evaporated under the reduced pressure to leave a brownish oil which was purified by flash column chromatography on silica using 5%-25% isopropanol/dichloromethane as a mobile phase, and the product was triturated with N,N-dimethylformamide to give tert-butyl 3-(4-amino-3-{4-[(5,7-dimethyl-1,3-benzoxazol-2-yl)amino]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-piperidinecarboxylate (0.28 g, 0.00051 mol). RP-HPLC (Delta Pak C18, 5 μm, 300 A, 15 cm; 5%-95% acetonitrile-0.1M ammonium acetate over 10 min, 1 mL/min) Rt 11.9 min.

後処理

  1. additionwere added
  2. temperatureto cool to ambient temperature
  3. customthe solvent was removed under the reduced pressure
  4. customThe residue was partitioned between water and dichloromethane
  5. extractionThe aqueous layer was extracted with dichloromethane (3×50 mL)
  6. washThe combined organic extracts were washed with water, saturated aqueous sodium bicarbonate solution, and brine
  7. dry with materialdried over magnesium sulfate
  8. customThe solvents were evaporated under the reduced pressure
  9. customto leave a brownish oil which
  10. customwas purified by flash column chromatography on silica using 5%-25% isopropanol/dichloromethane as a mobile phase
  11. customthe product was triturated with N,N-dimethylformamide

出典と根拠

ORDレコード
ord-5d91ac2e2c3e4e7ca1590a6e8fa351c0
出典データセット
uspto-grants-2005_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US06921763B2

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