1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (R)-3-{4-[1-(4-cyclohexylphenyl)-3-(4-trifluoromethylsulfanylphenyl)ureidomethyl]benzoylamino}-2-hydroxypropionic acid methyl ester

HRID 412446Notes

Reaction equation

HRID 412446 reaction equation
[CH:1]1([C:7]2[CH:12]=[CH:11][C:10]([CH:13]([NH:23][C:24]([NH:26][C:27]3[CH:32]=[CH:31][C:30]([S:33][C:34]([F:37])([F:36])[F:35])=[CH:29][CH:28]=3)=[O:25])[C:14]3[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][CH:15]=3)=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[CH3:60][O:61][C:62](=[O:67])[C@H:63]([OH:66])[CH2:64][NH2:65].C(N(C(C)C)CC)(C)C>CN(C=O)C.O.C(OCC)(=O)C>[CH3:60][O:61][C:62](=[O:67])[C@H:63]([OH:66])[CH2:64][NH:65][C:18](=[O:19])[C:17]1[CH:21]=[CH:22][C:14]([CH:13]([NH:23][C:24]([NH:26][C:27]2[CH:32]=[CH:31][C:30]([S:33][C:34]([F:37])([F:36])[F:35])=[CH:29][CH:28]=2)=[O:25])[C:10]2[CH:9]=[CH:8][C:7]([CH:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)=[CH:12][CH:11]=2)=[CH:15][CH:16]=1

Participants

9

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 223111524-[1-(4-Cyclohexylphenyl)-3-(4-trifluoromethylsulfanylphenyl)ureidomethyl]benzoic acidHCID 86590828(R)-methyl 3-amino-2-hydroxypropanoate hydrochloride

Product 1

HCID 67483231(R)-3-{4-[1-(4-cyclohexylphenyl)-3-(4-trifluoromethylsulfanylphenyl)ureidomethyl]benzoylamino}-2-hydroxypropionic acid methyl esterYield 86.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-[1-(4-Cyclohexylphenyl)-3-(4-trifluoromethylsulfanylphenyl)ureidomethyl]benzoic acid (0.32 g, 0.606 mmol) was dissolved in DMF (7 mL) and HOAt (0.10 g, 0.727 mmol) and EDAC (0.14 g, 0.727 mmol) were added. The mixture was stirred for 30 min. Then (R)-3-amino-2-hydroxypropionic acid methyl ester hydrochloride (0.14 g) and diisopropylethylamine (0.16 mL, 0.909 mmol) were added. The reaction was stirred overnight. The reaction mixture was transferred to a separatory funnel with ethyl acetate (30 mL) and water (15 mL) and extracted. The aqueous phase was extracted once more with ethyl acetate (15 mL) and the combined organic phases were washed with hydrochloric acid (0.2 N, 3×10 mL) and an aqueous solution of saturated sodium chloride (3×10 mL), dried over magnesium sulphate, filtered and concentrated in vacuo. The residue was purified on a column (silica gel, 30 g) using a mixture of ethyl acetate and n-heptane (200 mL, 40:60 and 450 mL 1:1) as eluent to afford 0.33 g of (R)-3-{4-[1-(4-cyclohexylphenyl)-3-(4-trifluoromethylsulfanylphenyl)ureidomethyl]benzoylamino}-2-hydroxypropionic acid methyl ester.

Workup

  1. stirringThe reaction was stirred overnight
  2. extractionextracted
  3. extractionThe aqueous phase was extracted once more with ethyl acetate (15 mL)
  4. washthe combined organic phases were washed with hydrochloric acid (0.2 N, 3×10 mL)
  5. dry with materialan aqueous solution of saturated sodium chloride (3×10 mL), dried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified on a column (silica gel, 30 g)
  9. additiona mixture of ethyl acetate and n-heptane (200 mL, 40:60 and 450 mL 1:1) as eluent

Sources & evidence

ORD record
ord-493dbb3a33b14d64aa4d247f9161c1dc
Source dataset
uspto-grants-2003_05
Patent number
US06562807B2

Reaction notes

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