Water → N2-(4-{4-amino-1-[1-(2-methoxyethyl)tetrahydro-1H-3-pyrrolyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide

HRID 2056204ノート

反応式

HRID 2056204 の反応式
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:32]3[CH2:36][CH2:35][NH:34][CH2:33]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)[C:3]=12.[CH3:37][O:38][CH2:39][CH2:40]Br.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:32]3[CH2:36][CH2:35][N:34]([CH2:40][CH2:39][O:38][CH3:37])[CH2:33]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)[C:3]=12

参加物

6

反応物 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 809722-Bromoethyl methyl etherHCID 22346925N2-[4-(4-amino-1-tetrahydro-1H-3-pyrrolyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-methoxyphenyl]-1-methyl-1H-2-indolecarboxamide

生成物 1

HCID 22347052N2-(4-{4-amino-1-[1-(2-methoxyethyl)tetrahydro-1H-3-pyrrolyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide収率 29.3%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
65 °C

実験手順

A suspension of N2-[4-(4-amino-1-tetrahydro-1H-3-pyrrolyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-methoxyphenyl]-1-methyl-1H-2-indolecarboxamide (0.250 g, 0.518 mmol) in dimethylformamide (5 mL) was treated with 2-bromoethyl methyl ether (0.079 g, 0.569 mmol) and potassium carbonate (0.143 g, 1.04 mmol). The reaction mixture was stirred at 65° C. for 18 h under a nitrogen atmosphere. Water (25 mL) was added to the reaction mixture. The precipitate formed was filtered and dried on the lyophilizer. The crude material was purified by flash chromatography on silica gel using 10% methanol in dichloromethane (15 min), 15% methanol in dichloromethane (15 min), 20% methanol in dichloromethane (20 min) and 50% methanol in dichloromethane (5 min) as the eluent. The column afforded 0.082 g (29%) of pure N2-(4-{4-amino-1-[1-(2-methoxyethyl)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 9.447 (s, 1H), 8.265 (s, 1H), 8.1278-8.1075 (d, 1H, J=8.12 Hz), 7.7192-7.6993 (d, 1H, J=7.96 Hz), 7.5996-7.5799 (d, 1H, J=7.88 Hz), 7.349-7.295 (m, 4H), 7.172-7.133 (m, 1H), 5.42 (m, 1H), 4.042 (s, 3H), 3.96 (s, 3H), 3.479 (m, 2H), 3.266-3.258 (m, 3H), 2.95-2.60 (m, 4H), 2.332 (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 2.34 min (100%), MH+ 541.3.

後処理

  1. customThe precipitate formed
  2. filtrationwas filtered
  3. customdried on the lyophilizer
  4. customThe crude material was purified by flash chromatography on silica gel using 10% methanol in dichloromethane (15 min), 15% methanol in dichloromethane (15 min)
  5. custom20% methanol in dichloromethane (20 min) and 50% methanol in dichloromethane (5 min)

出典と根拠

ORDレコード
ord-3a089f9800cc4b6cb492b1e059c9c535
出典データセット
uspto-grants-2008_02
特許番号
US07332497B2

反応ノート

読み込み中…