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

HRID 1869094Notes

Reaction equation

HRID 1869094 reaction equation
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]

Participants

7

Reactant 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, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
50 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-c550dd80b37d4e0b9ffb0c5bdfbeeeeb
Source dataset
uspto-grants-2009_12
Patent number
USRE041065E1

Reaction notes

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