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

HRID 1288885노트

반응식

HRID 1288885 반응식
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]

참가 물질

7

반응물 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, 화합물

생성물 1

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

시약·촉매·용매 1

HCID 176Acetic Acid용매

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온도
50 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-498350bde5ed4f2987a3daccd99a7b73
출처 데이터셋
uspto-grants-1998_05
특허 번호
US05747498

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