Water → 2-{2-[4-(3-Ethynyl-phenylamino)-6-(2-methoxy-ethoxy)-quinazolin-7-yloxy]-ethylsulfanyl}-propionic acid ammonium salt

HRID 1288885ノート

反応式

HRID 1288885 の反応式
Cl.Cl[CH2:3][CH2:4][O:5][C:6]1[CH:15]=[C:14]2[C:9]([C:10]([NH:16][C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([C:23]#[CH:24])[CH:18]=3)=[N:11][CH:12]=[N:13]2)=[CH:8][C:7]=1[O:25][CH2:26][CH2:27][O:28][CH3:29].[C:30](O)(=[S:34])[CH:31](C)O.[OH-:36].[K+].O.CN([CH:42]=[O:43])C>C(O)(=O)C>[NH4+:11].[C:23]([C:19]1[CH:18]=[C:17]([NH:16][C:10]2[C:9]3[C:14](=[CH:15][C:6]([O:5][CH2:4][CH2:3][S:34][CH:30]([CH3:31])[C:42]([O-:43])=[O:36])=[C:7]([O:25][CH2:26][CH2:27][O:28][CH3:29])[CH:8]=3)[N:13]=[CH:12][N:11]=2)[CH:22]=[CH:21][CH:20]=1)#[CH:24]

参加物

7

反応物 5

HCID 962WaterHCID 6228DimethylformamideHCID 14797Potassium HydroxideHCID 18925049[7-(2-Chloro-ethoxy)-6-(2-methoxy-ethoxy)-quinazolin-4-yl]-(3-ethynyl-phenyl)-amine HydrochlorideHCID 178473673HCID 178473673、化合物

生成物 1

HCID 1317206302-{2-[4-(3-Ethynyl-phenylamino)-6-(2-methoxy-ethoxy)-quinazolin-7-yloxy]-ethylsulfanyl}-propionic acid ammonium salt収率 18%

試薬・触媒・溶媒 1

HCID 176Acetic Acid溶媒

反応条件

温度
50 °C

実験手順

The title product of Example 34 (150 mg, 0.34 mmol) was added to a solution of thiolactic acid (100 μL, 1.14 mmol) and KOH (150 mg, 2.7 mmol) in degassed DMF (5 mL)/H2O (0.5 mL). The reaction mixture was stirred at 50° C. under an atmosphere of N2 for 72 hours and then cooled to room temperature. The pH of the mixture was adjusted to about 4.0 with acetic acid and then partitioned between CHCl3 and brine. The organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by preparative RP18 HPLC utilizing a gradient of 15% to 100% CH3CN/pH 4.5, 50 mM ammonium acetate followed by lyophilization of the appropriate pure fractions to afford the title product (28 mg; 18%; M.P. 95°-103° C. (dec); LC-MS: 468 (MH+); anal. RP-HPLC RT: 3.57 min).

後処理

  1. temperaturecooled to room temperature
  2. custompartitioned between CHCl3 and brine
  3. washThe organic extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by preparative RP18 HPLC

出典と根拠

ORDレコード
ord-498350bde5ed4f2987a3daccd99a7b73
出典データセット
uspto-grants-1998_05
特許番号
US05747498

反応ノート

読み込み中…