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Sodium Carbonate → N2-[4-(4-amino-1-tetrahydro-1H-3-pyrrolyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-methoxyphenyl]-1-methyl-1H-2-indolecarboxamide

HRID 898027
ノート
印刷プレビュー

反応式

HRID 898027 の反応式
Cl.I[C:3]1[C:11]2[C:6](=[N:7][CH:8]=[N:9][C:10]=2[NH2:12])[N:5]([CH:13]2[CH2:17][CH2:16][NH:15][CH2:14]2)[N:4]=1.[CH3:18][O:19][C:20]1[CH:25]=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:23]=[CH:22][C:21]=1[NH:35][C:36]([C:38]1[N:39]([CH3:47])[C:40]2[C:45]([CH:46]=1)=[CH:44][CH:43]=[CH:42][CH:41]=2)=[O:37].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>[NH2:12][C:10]1[N:9]=[CH:8][N:7]=[C:6]2[N:5]([CH:13]3[CH2:17][CH2:16][NH:15][CH2:14]3)[N:4]=[C:3]([C:24]3[CH:23]=[CH:22][C:21]([NH:35][C:36]([C:38]4[N:39]([CH3:47])[C:40]5[C:45]([CH:46]=4)=[CH:44][CH:43]=[CH:42][CH:41]=5)=[O:37])=[C:20]([O:19][CH3:18])[CH:25]=3)[C:11]=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 22347095N-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-methyl-1H-indole-2-carboxamideHCID 223473313-iodo-1-tetrahydro-1H-3-pyrrolyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine hydrochloride

生成物 1

HCID 22346925N2-[4-(4-amino-1-tetrahydro-1H-3-pyrrolyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-methoxyphenyl]-1-methyl-1H-2-indolecarboxamide収率 77.1%

試薬・触媒・溶媒 3

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

反応条件

温度
80 °C

実験手順

A suspension of 3-iodo-1-tetrahydro-1H-3-pyrrolyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine hydrochloride (2.186 g, 5.96 mmol) in ethylene glycol dimethyl ether (50 mL) was treated with N2-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-methyl-1H-2-indolecarboxamide (2.66 g, 6.56 mmol), tetrakis(triphenylphosphine)palladium (0.413 g, 0.358 mmol), and a solution of sodium carbonate (2.65 g, 25.03 mmol) in water (25 mL). The reaction mixture was stirred for 24 h at 80° C. The organic solvent was removed under reduced pressure. Dichloromethane (100 mL) and 1N sodium hydroxide (50 mL) were added. The product precipitated out of the aqueous layer. The aqueous layer was evaporated under reduced pressure. The resulting solid was washed with copious amounts of dichloromethane and ethyl acetate. The organic solvent was removed under reduced pressure to give 2.218 g (77%) of pure N2-[4-(4-amino-1-tetrahydro-1H-3-pyrrolyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-methoxyphenyl]-1-methyl-1H-2-indolecarboxamide. 1H NMR (DMSO-d6, 400 MHz) δ 9.443 (s, 1H), 8.256 (s, 1H), 8.1168-8.0965 (d, 1H, J=8.12 Hz), 7.7181-7.6983 (d, 1H, J=7.92 Hz), 7.598-7.5778 (d, 1H, J=8.08 Hz), 7.349-7.291 (m, 4H), 7.171-7.132 (m, 1H), 5.332-5.313 (m, 1H), 4.041 (s, 3H), 3.96 (s, 3H), 3.224-3.058 (m, 3H), 2.926-2.910 (m, 1H), 2.213-2.158 (m, 2H); LCMS (Thermoquest AQA single-quad MS, Genesis C18 column, 3 μm particle size, 33×4.6 mm; 70% 50 mM ammonium acetate in water to 95% acetonitrile over 6 min, 0.8 to 0.5 mL/min) Rt 2.09 min (100%), MH+ 483.3.

後処理

  1. customThe organic solvent was removed under reduced pressure
  2. additionDichloromethane (100 mL) and 1N sodium hydroxide (50 mL) were added
  3. customThe product precipitated out of the aqueous layer
  4. customThe aqueous layer was evaporated under reduced pressure
  5. washThe resulting solid was washed with copious amounts of dichloromethane and ethyl acetate
  6. customThe organic solvent was removed under reduced pressure

出典と根拠

ORDレコード
ord-0217cc4b24fa4187bbb7862684696bf6
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

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