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

HRID 897895ノート

反応式

HRID 897895 の反応式
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][CH2:15][N:14]([CH3:18])[CH2:13]2)[N:3]=1.[CH3:19][C:20]1[CH:21]=[C:22]([CH3:45])[C:23]2[O:27][C:26]([NH:28][C:29]3[CH:34]=[CH:33][C:32](B4OC(C)(C)C(C)(C)O4)=[CH:31][CH:30]=3)=[N:25][C:24]=2[CH:44]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=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][CH2:15][N:14]([CH3:18])[CH2:13]3)[N:3]=[C:2]([C:32]3[CH:31]=[CH:30][C:29]([NH:28][C:26]4[O:27][C:23]5[C:22]([CH3:45])=[CH:21][C:20]([CH3:19])=[CH:44][C:24]=5[N:25]=4)=[CH:34][CH:33]=3)[C:10]=12

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]-amineHCID 223473453-iodo-1-(1-methyl-3-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

生成物 1

HCID 22347343N2-{4-[4-amino-1-(1-methyl-3-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]phenyl}-5,7-dimethyl-1,3-benzoxazol-2-amine収率 12%

試薬・触媒・溶媒 3

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 962Water溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
80 °C

実験手順

A mixture of 3-iodo-1-(1-methyl-3-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.35 g, 0.001 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 (0.44 g, 0.0012 mol), tetrakis(triphenylphosphine)-palladium (0.058 g, 0.00005 mol) and sodium carbonate (0.27 g, 0.0025 mol) in ethylene glycol dimethyl ether (30 mL) and water (6 mL) was heated at 80° C. for 16 hours under an atmosphere of nitrogen. 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 2%-10% methanol/dichloromethane as a mobile phase to give N2-{4-[4-amino-1-(1-methyl-3-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]phenyl}-5,7-dimethyl-1,3-benzoxazol-2-amine (0.055 g, 0.00012 mol). 1H NMR (DMSO-d6, 400 MHz) δ 10.80 (s, 1H), 8.22 (s, 1H), 7.95 (d, 2H), 7.65 (d, 2H), 7.15 (s, 1H), 6.80 (s, 1H), 4.80 (br, 1H), 2.95 (br, 1H), 2.85 (br, 1H), 2.45 (br, 1H), 2.40 (s, 3H), 2.35 (s, 3H), 2.25 (s, 3H), 2.00 (br, 3H), 1.80 (br, 1H), 1.70 (br, 1H). 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 9.7 min. MS: MH+ 469

後処理

  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 2%-10% methanol/dichloromethane as a mobile phase

出典と根拠

ORDレコード
ord-6819f696a87043229273b16b3f24b7ea
出典データセット
uspto-grants-2005_07
特許番号
US06921763B2

反応ノート

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