Hydrochloric Acid → ZD 7114 hydrochloride

HRID 1651126Notes

Reaction equation

HRID 1651126 reaction equation
[OH:1][CH:2]([CH2:20][O:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH2:3][NH:4][CH2:5][CH2:6][O:7][C:8]1[CH:19]=[CH:18][C:11]([O:12][CH2:13][C:14]([O:16]C)=O)=[CH:10][CH:9]=1.[CH3:28][O:29][CH2:30][CH2:31][NH2:32].CCOCC.[ClH:38]>ClCCl>[ClH:38].[OH:1][C@H:2]([CH2:20][O:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH2:3][NH:4][CH2:5][CH2:6][O:7][C:8]1[CH:9]=[CH:10][C:11]([O:12][CH2:13][C:14]([NH:32][CH2:31][CH2:30][O:29][CH3:28])=[O:16])=[CH:18][CH:19]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 80182-MethoxyethylamineHCID 132305HCID 132305, compound

Product 1

HCID 9890216ZD 7114 hydrochloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(-)-Methyl 4-[2-(2-hydroxy-3-phenoxypropylamino)ethoxy]phenoxyacetate (44.0 g) (the same starting material as in Example 2) and 2-methoxyethylamine (30 ml) were heated together on a steam-bath for 24 hours. The mixture was cooled and evaporated under reduced pressure to give an oily residue. This was dissolved in dichloromethane (200 ml) and treated with a solution of ether saturated with hydrogen chloride. The solvent was evaporated and the residual solid crystallised from a mixture of methanol and ethyl acetate to give (S)-4-[2-(2-hydroxy-3-phenoxypropylamino)ethoxy]-N-(2-methoxyethyl)phenoxyacetamide hydrochloride (39.2 g), m.p. 171°-3° C.; αD =-10.7° (c=1.0; methanol); microanalysis: found C, 58.1; H, 7.0; N, 6.0; Cl, 7.9%; required for C22H31ClN2O6 : C, 58.1; H, 6.9; N, 6.2; Cl 7.8%: NMR (DMSO-d6) 3.1(m,1H, CHCH2NH); 3.24(s, 3H,OCH3); 3.24-3.45(m,7H,CHCH2NHCH2 ; NHCH2CH2OCH3); 4.0(m,2H, ArOCH2CHOH); 4.2-4.35(m,3H,CHOH; CH2CH2OAr); 5.95(d,1H,OH); 6.85-7.05(m,7H,Ar); 7.3(m,2H,Ar); 8.15(t,1H, CONHCH2); 9.16 and 9.35 (broad peaks, 2H, NH2+).

Workup

  1. temperaturewere heated together on a steam-bath for 24 hours
  2. temperatureThe mixture was cooled
  3. customevaporated under reduced pressure
  4. customto give an oily residue
  5. customThe solvent was evaporated
  6. customthe residual solid crystallised from a mixture of methanol and ethyl acetate

Sources & evidence

ORD record
ord-c833be35e4444e50ba30f65e285e0347
Source dataset
uspto-grants-1990_05
Patent number
US04927836

Reaction notes

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