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Sodium Carbonate → N2-(4-{4-amino-1-[1-(2-methoxyethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenyl)-5,7-dimethyl-1,3-benzoxazol-2-amine

HRID 2056087
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HRID 2056087 반응식
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([CH:12]2[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][O:20][CH3:21])[CH2:14][CH2:13]2)[N:3]=1.[CH3:22][C:23]1[CH:24]=[C:25]([CH3:48])[C:26]2[O:30][C:29]([NH:31][C:32]3[CH:37]=[CH:36][C:35](B4OC(C)(C)C(C)(C)O4)=[CH:34][CH:33]=3)=[N:28][C:27]=2[CH:47]=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>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([CH:12]3[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][O:20][CH3:21])[CH2:14][CH2:13]3)[N:3]=[C:2]([C:35]3[CH:34]=[CH:33][C:32]([NH:31][C:29]4[O:30][C:26]5[C:25]([CH3:48])=[CH:24][C:23]([CH3:22])=[CH:47][C:27]=5[N:28]=4)=[CH:37][CH:36]=3)[C:10]=12
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참가 물질

8

반응물 3

HCID 10340Sodium CarbonateHCID 11581347(5,7-Dimethyl-benzoxazol-2-yl)-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-amine2회HCID 223469673-iodo-1-[1-(2-methoxyethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine

생성물 1

HCID 22346838N2-(4-{4-amino-1-[1-(2-methoxyethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenyl)-5,7-dimethyl-1,3-benzoxazol-2-amine수율 54%

시약·촉매·용매

4
HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

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온도
80 °C

실험 절차

A mixture of 3-iodo-1-[1-(2-methoxyethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.2 g, 0.0005 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 (0.28 g, 0.00078 mol), tetrakis(triphenylphosphine)palladium (0.029 g, 0.000025 mol) and sodium carbonate (0.13 g, 0.00125 mol) in ethylene glycol dimethyl ether (25 mL) and water (5 mL) was heated at 80° C. for 5 hours under an atmosphere of nitrogen. Additional N-(5,7-dimethyl-1,3-benzoxazol-2-yl)-N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]amine (0.14 g, 0.00039 mol.) and tetrakis(triphenylphosphine)-palladium (0.015 g, 0.0000125 mol) were added, and the mixture was stirred at 80° C. for 16 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 (2×50 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 solid which was purified by flash column chromatography on silica using 5%-20% methanol/dichloromethane as a mobile phase to give N2-(4-{4-amino-1-[1-(2-methoxyethyl)-4-piperidyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenyl)-5,7-dimethyl-1,3-benzoxazol-2-amine (0.14 g, 0.00027 mol). 1H NMR (TFA-d, 400 MHz) δ 8.53 (s, 1H), 7.88 (m, 2H), 7.81 (m, 2H), 7.14 (s, 2H), 5.40 (br, 1H), 4.05 (m, 2H), 3.98 (m, 2H), 3.66 (m, 2H), 3.56 (s, 3H), 3.47 (m, 2H), 2.96 (m, 2H), 2.54 (br, 2H), 2.50 (s, 3H), 2.43 (s, 3H). RP-HPLC (Delta Pak C18, 5 μm, 300A, 15 cm; 5%-95% acetonitrile—0.1M ammonium acetate over 10 min, 1 mL/min) Rt 9.6 min. MS: MH+ 513

후처리

  1. temperatureto cool to ambient temperature
  2. customthe solvent was removed under the reduced pressure
  3. customThe residue was partitioned between water and dichloromethane
  4. extractionThe aqueous layer was extracted with dichloromethane (2×50 mL)
  5. washThe combined organic extracts were washed with water, saturated aqueous sodium bicarbonate solution, and brine
  6. dry with materialdried over magnesium sulfate
  7. customThe solvents were evaporated under the reduced pressure
  8. customto leave a brownish solid which
  9. customwas purified by flash column chromatography on silica using 5%-20% methanol/dichloromethane as a mobile phase

출처 및 근거

ORD 기록
ord-cf9421f67ec748da9ded86eb5dae4980
출처 데이터셋
uspto-grants-2008_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07332497B2

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