1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (R)-3-{4-[1-(4-cyclohexylphenyl)-3-(3-methoxy-5-trifluoromethylphenyl)ureidomethyl]benzoylamino}-2-hydroxypropionic acid ethyl ester

HRID 967628Notes

Reaction equation

HRID 967628 reaction equation
C1([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[CH:13]([NH:23][C:24]([NH:26][C:27]2[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:30]=[C:29]([O:37][CH3:38])[CH:28]=2)=[O:25])[C:14]2[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][CH:15]=2)CCCCC1.[CH:39]1[CH:40]=[CH:41][C:42]2N(O)N=N[C:43]=2[CH:44]=1.CCN=C=NCCCN(C)C.[CH2:60]([O:62][C:63](=[O:68])[C@H:64]([OH:67])[CH2:65][NH2:66])[CH3:61]>CN(C=O)C.C(OCC)(=O)C.O>[CH2:60]([O:62][C:63](=[O:68])[C@H:64]([OH:67])[CH2:65][NH:66][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]=[C:31]([C:33]([F:34])([F:35])[F:36])[CH:30]=[C:29]([O:37][CH3:38])[CH:28]=2)=[O:25])[C:8]2[CH:9]=[CH:10][C:11]([CH:39]3[CH2:40][CH2:41][CH2:42][CH2:43][CH2:44]3)=[CH:12][CH:7]=2)=[CH:15][CH:16]=1)[CH3:61]

Participants

8

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 223111384-[1-(Cyclohexylphenyl)-3-(3-methoxy-5-trifluoromethylphenyl)ureidomethyl]benzoic acidHCID 54263093ethyl (2R)-3-amino-2-hydroxypropanoate

Product 1

HCID 67483036(R)-3-{4-[1-(4-cyclohexylphenyl)-3-(3-methoxy-5-trifluoromethylphenyl)ureidomethyl]benzoylamino}-2-hydroxypropionic acid ethyl esterYield 99.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

4-[1-(Cyclohexylphenyl)-3-(3-methoxy-5-trifluormethylphenyl)ureidomethyl]benzoic acid (420 mg, 0.8 mmol) was dissolved in DMF (10 mL), and then HOBt (160 mg, 1.2 mmol) and EDAC (230 mg, 1.2 mmol) were added. The reaction mixture was allowed to stand for 30 min, then (R)-isoserine ethyl ester (260 mg, 1.2 mmol) and dissopropylethylamine (210 mL, 1.2 mmol) dissolved in DMF (5 mL) were added and the reaction mixture was stirred at room temperature for 16 hours. Water (50 mL) and ethyl acetate (100 mL) were added and the organic phase was washed with water (5×50 mL), dried (magnesium sulphate), filtered and evaporated in vacuo. The residue was purified by column chromatography on silica gel, eluting with a mixture of heptane and ethyl acetate (1:3) to afford 510 mg of (R)-3-{4-[1-(4-cyclohexylphenyl)-3-(3-methoxy-5-trifluoromethylphenyl)ureidomethyl]benzoylamino}-2-hydroxypropionic acid ethyl ester as an amorphous solid.

Workup

  1. additionwere added
  2. washthe organic phase was washed with water (5×50 mL)
  3. dry with materialdried (magnesium sulphate)
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe residue was purified by column chromatography on silica gel
  7. washeluting with a mixture of heptane and ethyl acetate (1:3)

Sources & evidence

ORD record
ord-5828315428a943eb9238a822a9c4c7bf
Source dataset
uspto-grants-2005_10
Patent number
US06953812B2

Reaction notes

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