Trifluoroacetic acid → HCID 17984396, compound

HRID 1181081Notes

Reaction equation

HRID 1181081 reaction equation
C[O:2][C:3](=[O:29])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][CH2:14][C:15]2[N:16]=[C:17]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[O:18][C:19]=2[CH3:20])=[C:8]([CH2:27][NH2:28])[CH:7]=1.FC(F)(F)C(O)=O.C(N(CC)CC)C.[Cl:44][C:45]1[S:46][C:47]([Cl:53])=[CH:48][C:49]=1[C:50](Cl)=[O:51].CNCCNC>C(Cl)Cl.C(Cl)Cl.CO.CO>[Cl:44][C:45]1[S:46][C:47]([Cl:53])=[CH:48][C:49]=1[C:50]([NH:28][CH2:27][C:8]1[CH:7]=[C:6]([CH2:5][CH2:4][C:3]([OH:2])=[O:29])[CH:11]=[CH:10][C:9]=1[O:12][CH2:13][CH2:14][C:15]1[N:16]=[C:17]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:18][C:19]=1[CH3:20])=[O:51]

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8070N,N'-DimethylethylenediamineHCID 8471TriethylamineHCID 27770842,5-Dichlorothiophene-3-carbonyl chlorideHCID 58979451HCID 58979451, compound2×

Product 1

HCID 17984396HCID 17984396, compoundYield 26%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×HCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
55 °C

Procedure

General Parallel Synthesis Procedure: 3-{3-Aminomethyl-4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenyl}-propionic acid methyl ester: trifluoroacetic acid salt (565 mg, 1.1 mmol) was dissolved in CH2Cl2 (25 mL) and washed with saturated NaHCO3 solution (15 mL). The organic layer was dried (NaSO4), filtered, and concentrated to 3-{3-aminomethyl-4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenyl}-propionic acid methyl ester (368 mg, 0.93 mmol, 84%). A portion of this free base (26 mg, 0.071 mmol) in CH2Cl2 (0.5 mL) was treated with triethylamine (0.075 mL, 0.54 mmol) then 2,5-dichloro-thiophene-3-carbonyl chloride (0.049 mL, 0.22 mmol). The reaction mixture was shaken overnight and dimethylethylenediamine (0.15 mL, 1.4 mmol) was added. The reaction mixture was shaken for 2 h and passed through an SCX column (1 g, equilibrated with 2 mL MeOH then 2 mL MeOH/CH2Cl2 1/1). The methyl ester-amide product was eluted with MeOH/CH2Cl2 (1:1, 10 mL) and concentrated. The residue was dissolved in THF (2 mL) and MeOH (2 mL) and treated with 5N NaOH (1 mL). The solution was heated at 55° C. for 2.5 h, cooled, and acidified with 5N HCl (1.5 mL). The mixture was transferred to a ChemElute cartridge and eluted with CH2Cl2. The solvent was removed under a stream of N2. The crude product was dried under vacuum and purified by mass-directed HPLC to give the title compound as a foam (9.9 mg, 26%).) MS (ESI) m/z 559.1 (M+H)+.

Workup

  1. customGeneral Parallel Synthesis Procedure
  2. washwashed with saturated NaHCO3 solution (15 mL)
  3. dry with materialThe organic layer was dried (NaSO4)
  4. filtrationfiltered
  5. stirringThe reaction mixture was shaken for 2 h
  6. washThe methyl ester-amide product was eluted with MeOH/CH2Cl2 (1:1, 10 mL)
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in THF (2 mL)
  9. additionMeOH (2 mL) and treated with 5N NaOH (1 mL)
  10. temperaturecooled
  11. washeluted with CH2Cl2
  12. customThe solvent was removed under a stream of N2
  13. dry with materialThe crude product was dried under vacuum
  14. custompurified by mass-directed HPLC

Sources & evidence

ORD record
ord-5eccf88a33954ff19dff456e44820bbd
Source dataset
uspto-grants-2007_10
Patent number
US07282501B2

Reaction notes

Loading…