Sodium Carbonate → HCID 178488202、化合物

HRID 432315ノート

反応式

HRID 432315 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]([C@H:12]2[CH2:17][CH2:16][C@@H:15]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[CH2:14][CH2:13]2)[N:3]=1.[CH3:25][O:26][C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][C:32]=1[N:33]([CH3:44])[C:34](=[O:43])[CH2:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=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]([C@H:12]3[CH2:17][CH2:16][C@@H:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[CH2:14][CH2:13]3)[N:3]=[C:2]([C:29]3[CH:30]=[CH:31][C:32]([N:33]([CH3:44])[C:34](=[O:43])[CH2:35][CH2:36][C:37]4[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=4)=[C:27]([O:26][CH3:25])[CH:28]=3)[C:10]=12

参加物

7

反応物 3

HCID 10340Sodium CarbonateHCID 223472033-Methoxy-4-[methyl(3-phenylpropanoyl)amino]phenylboronic acidHCID 178481014HCID 178481014、化合物

生成物 1

HCID 178488202HCID 178488202、化合物収率 10%

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
85 °C

実験手順

A solution of cis-3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.293 g, 0.664 mmol) in ethylene glycol dimethyl ether (10 mL) was treated with 3-methoxy-4-[methyl(3-phenylpropanoyl)amino]phenylboronic acid (0.290 g, 0.730 mmol), tetrakis(triphenylphosphine)palladium (0.046 g, 0.040 mmol), and a solution of sodium carbonate (0.169 g, 1.59 mmol) in water (5 mL). The reaction mixture was stirred over night at 85° C. under a nitrogen atmosphere. The solvent was removed under reduced pressure, and ethyl acetate was added to the aqueous layer. The layers were partitioned, and the aqueous layer was extracted with ethyl acetate (150 mL). The combined organic layers were washed with water and brine, dried over magnesium sulfate, filtered, and evaporated under reduced pressure. The crude product was purified by flash chromatography on silica gel using 4% methanol in dichloromethane, 8% methanol in dichloromethane, and then 12% methanol in dichloromethane as eluent. A second column using a Supelco flash chromatography silica gel column using 30% methanol in dichloromethane afforded 0.037 g (10%) of cis-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-N1-methyl-3-phenylpropanamide. 1H NMR (CDCl3, 400 MHz) δ 8.374 (s, 1H), 7.315-7.312 (m, 1H), 7.285-7.213 (m, 3H), 7.174-7.087 (m, 4H), 5.795 (br, s, 2H), 4.965-4.922 (m, 1H), 3.892 (s, 3H), 3.213 (s, 3H), 2.948-2.918 (m, 2H), 2.667 (m, 6H), 2.455-2.349 (m, 10H), 2.25-2.15 (m, 2H), 1.867-1.845 (m, 2H), 1.718-1.710 (m, 2H); HPLC Waters 2690 Alliance HPLC (Symmetry Shield RP18 3.5 μm, 2.1×50 mm; 5%-95% acetonitrile-0.1 M ammonium acetate over 15 min, 0.5 mL/min) Rt 4.947 min (98%).

後処理

  1. customThe solvent was removed under reduced pressure, and ethyl acetate
  2. additionwas added to the aqueous layer
  3. customThe layers were partitioned
  4. extractionthe aqueous layer was extracted with ethyl acetate (150 mL)
  5. washThe combined organic layers were washed with water and brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customThe crude product was purified by flash chromatography on silica gel using 4% methanol in dichloromethane, 8% methanol in dichloromethane

出典と根拠

ORDレコード
ord-eb08315a702d4f0a9104725571dc83e2
出典データセット
uspto-grants-2003_12
特許番号
US06660744B1

反応ノート

読み込み中…