1,2-Dimethoxyethane → HCID 178480993、化合物

HRID 897507ノート

反応式

HRID 897507 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.CC1(C)C(C)(C)OB([C:33]2[CH:47]=[CH:46][C:36]([O:37][C:38]3[CH:45]=[CH:44][CH:43]=[CH:42][C:39]=3[C:40]#[N:41])=[CH:35][CH:34]=2)O1.COCCOC.O.C(=O)([O-])[O-].[Na+].[Na+]>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:33]3[CH:47]=[CH:46][C:36]([O:37][C:38]4[CH:45]=[CH:44][CH:43]=[CH:42][C:39]=4[C:40]#[N:41])=[CH:35][CH:34]=3)[C:10]=12

参加物

7

反応物 4

HCID 80711,2-DimethoxyethaneHCID 2735133Sodium Carbonate MonohydrateHCID 223467172-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]benzonitrileHCID 178481014HCID 178481014、化合物

生成物 1

HCID 178480993HCID 178480993、化合物収率 67.8%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒2 回HCID 962Water溶媒

反応条件

温度
85 °C

実験手順

A mixture of cis-3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (2.29 g, 5.19 mmol, 1 equiv), 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]benzonitrile (2.0 g, 6.2 mmol, 1.2 equiv), tetrakis(triphenylphosphine)palladium (0.329 g, 0.311 mmol, 0.06 equiv), DME (21 mL), and sodium carbonate monohydrate (1.54 g, 12.5 mmol, 2.4 equiv) in water (16 mL) was heated at 85° C. for 60 h. Additional tetrakis(triphenylphosphine)palladium (0.100 g, 0.02 equiv) was added and the reaction mixture was heated at 85° C. for 6.5 h. The reaction mixture was allowed to cool to ambient temperature and was partitioned between saturated aqueous sodium bicarbonate solution (25 mL) and EtOAc (25 mL). The organic extract was dried over MgSO4, filtered, and concentrated. The residue was triturated from Et2O and purified by column chromatography on silica gel (elution with 1 L of 5% MeOH/CH2Cl2, 1L of 10% MeOH/CH2Cl2, 1 L of 20% MeOH/CH2Cl2, and 1 L of 25% MeOH/CH2Cl2) to give cis-2-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenoxy)benzonitrile as a pale yellow solid (1.79 g, 3.52 mmol): 1H NMR (d6 DMSO, 400 MHz): δH 8.24 (1H, s), 7.94 (1H, d, J=7.7 Hz), 7.68-7.73 (3H, m), 7.31-7.34 (3H, m), 7.18 (1H, d, J=8.5 Hz), 4.78-4.83 (1H, m), 2.21-2.51 (11H, m), 2.19 (3H, s), 2.05-2.08 (2H, m), 1.56-1.71 (4H, m); RP-HPLC (Delta Pak C18, 5 μm, 300 Å, 15 cm; 5%-85% acetonitrile-0.1M ammonium acetate over 20 min, 1 mL/min) Rt 13.16 min. MS: MH+ 509.

後処理

  1. temperaturethe reaction mixture was heated at 85° C. for 6.5 h
  2. temperatureto cool to ambient temperature
  3. customwas partitioned between saturated aqueous sodium bicarbonate solution (25 mL) and EtOAc (25 mL)
  4. extractionThe organic extract
  5. dry with materialwas dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was triturated from Et2O
  9. custompurified by column chromatography on silica gel (elution with 1 L of 5% MeOH/CH2Cl2, 1L of 10% MeOH/CH2Cl2, 1 L of 20% MeOH/CH2Cl2, and 1 L of 25% MeOH/CH2Cl2)

出典と根拠

ORDレコード
ord-a76565be27b34bc2b9b9d3caccb08a66
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…