Sodium Carbonate → N2-(4-{4-amino-1-[3-(1H-1-imidazolyl)propyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide

HRID 898024ノート

反応式

HRID 898024 の反応式
[N:1]1([CH2:6][CH2:7][CH2:8][N:9]2[C:13]3=[N:14][CH:15]=[N:16][C:17]([NH2:18])=[C:12]3[C:11](I)=[N:10]2)[CH:5]=[CH:4][N:3]=[CH:2]1.[CH3:20][O:21][C:22]1[CH:27]=[C:26](B2OC(C)(C)C(C)(C)O2)[CH:25]=[CH:24][C:23]=1[NH:37][C:38]([C:40]1[N:41]([CH3:49])[C:42]2[C:47]([CH:48]=1)=[CH:46][CH:45]=[CH:44][CH:43]=2)=[O:39].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>[NH2:18][C:17]1[N:16]=[CH:15][N:14]=[C:13]2[N:9]([CH2:8][CH2:7][CH2:6][N:1]3[CH:5]=[CH:4][N:3]=[CH:2]3)[N:10]=[C:11]([C:26]3[CH:25]=[CH:24][C:23]([NH:37][C:38]([C:40]4[N:41]([CH3:49])[C:42]5[C:47]([CH:48]=4)=[CH:46][CH:45]=[CH:44][CH:43]=5)=[O:39])=[C:22]([O:21][CH3:20])[CH:27]=3)[C:12]=12

参加物

7

反応物 3

HCID 10340Sodium CarbonateHCID 223469111-[3-(1H-1-imidazolyl)propyl]-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amineHCID 22347095N-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-methyl-1H-indole-2-carboxamide

生成物 1

HCID 22346894N2-(4-{4-amino-1-[3-(1H-1-imidazolyl)propyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide収率 49.4%

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 1-[3-(1H-1-imidazolyl)propyl]-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.086 g, 0.233 mmol) in ethylene glycol dimethyl ether (4 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 (0.104 g, 0.256 mmol), tetrakis(triphenylphosphine)palladium (0.016 g, 0.014 mmol), and a solution of sodium carbonate (0.059 g, 0.56 mmol) in water (2 mL). The reaction mixture was stirred for 24 h at 80° C. The organic solvent was removed under reduced pressure and dichloromethane (25 mL) was added. The layers were partitioned and the aqueous layer was extracted with dichloromethane (100 mL). The combined organic layers were dried over magnesium sulfate, filtered and evaporated under reduced pressure. The crude material was purified by flash chromatography on silica gel using a step-wise gradient of 5% methanol in dichloromethane to 50% methanol in dichloromethane on a 10 g ISCO column. The column afforded 0.06 g (49%) of pure N2-(4-{4-amino-1-[3-(1H-1-imidazolyl)propyl]-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), 8.278 (s, 1H), 8.1324-8.1121 (d, 1H, J=8.12 Hz), 7.744-7.699 (m, 2H), 7.6-7.579 (d, 1H, J=8.4 Hz), 7.365-7.283 (m, 5H), 7.172-7.135 (m, 1H), 6.939 (s, 1H), 4.36-4.326 (m, 2H), 4.079-4.019 (m, 5H), 3.964 (s, 3H), 2.324-2.309 (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 2.25 min (100%), MH+ 522.3.

後処理

  1. customThe organic solvent was removed under reduced pressure and dichloromethane (25 mL)
  2. additionwas added
  3. customThe layers were partitioned
  4. extractionthe aqueous layer was extracted with dichloromethane (100 mL)
  5. dry with materialThe combined organic layers were dried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe crude material was purified by flash chromatography on silica gel using a step-wise gradient of 5% methanol in dichloromethane to 50% methanol in dichloromethane on a 10 g ISCO column

出典と根拠

ORDレコード
ord-0529633c05344d5db3d2fdde0dc5099f
出典データセット
uspto-grants-2005_07
特許番号
US06921763B2

反応ノート

読み込み中…