Hydrochloric Acid → ZD 7114 hydrochloride

HRID 1110719Notes

Reaction equation

HRID 1110719 reaction equation
C[CH:2]([O:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH2:15][NH:16][CH2:17][CH:18]([OH:27])[CH2:19][O:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:9][CH:8]=1)[C:3]([O-:5])=O.[CH3:28][O:29][CH2:30][CH2:31][NH2:32].CCOCC.[ClH:38]>ClCCl>[ClH:38].[OH:27][C@H:18]([CH2:19][O:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH2:17][NH:16][CH2:15][CH2:14][O:13][C:10]1[CH:11]=[CH:12][C:7]([O:6][CH2:2][C:3]([NH:32][CH2:31][CH2:30][O:29][CH3:28])=[O:5])=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 80182-MethoxyethylamineHCID 22154110HCID 22154110, 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.; αS =-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,3 H,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-056abeb01acf4e92a9ebb57f43c12378
Source dataset
uspto-grants-1990_12
Patent number
US04977148

Reaction notes

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