Sodium Carbonate → HCID 178428809、化合物

HRID 51539

反応式

HRID 51539 の反応式
I[C:2]1[C:10]2[C:9]([NH2:11])=[N:8][CH:7]=[N:6][C:5]=2[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)[CH:3]=1.[C:25]1([O:31][C:32]2[CH:37]=[CH:36][C:35](B3OC(C)(C)C(C)(C)O3)=[C:34]([CH3:47])[CH:33]=2)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.O>[CH3:47][C:34]1[CH:33]=[C:32]([O:31][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:37]=[CH:36][C:35]=1[C:2]1[C:10]2[C:9]([NH2:11])=[N:8][CH:7]=[N:6][C:5]=2[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)[CH:3]=1

参加物

6

反応物 3

HCID 10340Sodium CarbonateHCID 227364244,4,5,5-Tetramethyl-2-(2-methyl-4-phenoxyphenyl)-1,3,2-dioxaborolaneHCID 178480948HCID 178480948、化合物

生成物 1

HCID 178428809HCID 178428809、化合物収率 96.1%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

A mixture of trans-5-iodo-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine (0.347 g, 0.000788 mol), 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl phenyl ether (0.27 g, 0.000867 mol), tetrakis(triphenyl-phosphine)palladium(0) (0.054 g, 0.000047 mmol), and sodium carbonate (0.209 g, 0.00197 mol) in N,N-dimethylformamide (15 mL) and water (10 mL) was heated at 80° C. under an atmosphere of nitrogen for 16 hours. The mixture was allowed to cool to ambient temperature and the solvent removed under reduced pressure. The residue was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate. The water phase was further extracted with ethyl acetate and the combined organic extracts were dried over sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by flash chromatography on silica gel using triethylamine/dichloromethane (5:95) followed by methanol/triethylamine/ dichloromethane (3:5:92) as mobile phase to yield trans-5-(2-methyl-4-phenoxyphenyl)-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine (0.376 g, 0.000757 mol). Trans-5-(2-methyl-4-phenoxyphenyl)-7-[4-(4-methylpiperazino)-cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine (0.376 g, 0.000757 mol) was dissolved in refluxing ethanol (10 mL) and a preheated solution of maleic acid (0.264 g, 0.00227 mol) in ethanol (5 mL) was added. The mixture was refluxed for 15 minutes, cooled to ambient temperature and the precipitate collected by filtration, washed with cool ethanol and dried to give trans-5-(2-methyl-4-phenoxyphenyl)-7-[4-(4-methylpiperazino)-cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine trimaleate (0.153 g, 0.000181 mol): 1H NMR (DMSO-d6, 400 MHz) 8.22 (s, 1H), 7.42 (m, 3H), 7.25 (d, 1H), 7.17 (t, 1H), 7.09 (d, 2H), 7.02 (s, 1H), 6.89 (d, 1H), 6.16 (s, 6H), 4.58 (m, 1H), 3.3 (br, 9H), 2.68 (s, 3H), 2.22 (s, 3H), 2.01 (br, 6H), 1.57 (br, 2H) RP-HPLC (Hypersil C18, 5 μm, 250×4.6 mm; 25%-100% over 23 min with 0.1 M ammonium acetate, 1 mL/min) Rt 7.30 min. MS: MH+497.

後処理

  1. temperatureto cool to ambient temperature
  2. customthe solvent removed under reduced pressure
  3. customThe residue was partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate
  4. extractionThe water phase was further extracted with ethyl acetate
  5. dry with materialthe combined organic extracts were dried over sodium sulfate
  6. customThe solvent was removed under reduced pressure
  7. customthe residue was purified by flash chromatography on silica gel

出典と根拠

ORDレコード
ord-ebeb21a3975b4333a9dbc4e08e815258
出典データセット
uspto-grants-2004_03
特許番号
US06713474B2

関連ノート

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