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

HRID 967635Notes

Reaction equation

HRID 967635 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:33])[N:10]([CH2:23][C:24]2[CH:32]=[CH:31][C:27]([C:28](O)=[O:29])=[CH:26][CH:25]=2)[C:11]2[CH:16]=[CH:15][C:14]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)=[CH:13][CH:12]=2)[CH:5]=[CH:6][CH:7]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.Cl.[CH2:56]([O:58][C:59](=[O:64])[C@H:60]([OH:63])[CH2:61][NH2:62])[CH3:57].C(N(CC)C(C)C)(C)C>CN(C=O)C.C(OCC)(=O)C>[CH2:56]([O:58][C:59](=[O:64])[C@H:60]([OH:63])[CH2:61][NH:62][C:28](=[O:29])[C:27]1[CH:31]=[CH:32][C:24]([CH2:23][N:10]([C:11]2[CH:12]=[CH:13][C:14]([CH:17]3[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]3)=[CH:15][CH:16]=2)[C:9]([NH:8][C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Br:1])[CH:3]=2)=[O:33])=[CH:25][CH:26]=1)[CH3:57]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 223110904-[3-(3-Bromophenyl)-1-(4-cyclohexylphenyl)ureidomethyl]benzoic acidHCID 86586063(R)-isoserine ethyl ester hydrochloride

Product 1

HCID 67483100(R)-3-{4-[3-(3-bromophenyl)-1-(4-cyclohexylphenyl)ureidomethyl]benzoylamino}-2-hydroxypropionic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

4-[3-(3-Bromophenyl)-1-(4-cyclohexylphenyl)ureidomethyl]benzoic acid (0.20 g, 0.39 mmol) was dissolved in DMF (2.5 mL) and EDAC (0.12 g, 0.6 mmol) and HOBt (0.089 mg, 0.6 mmol) were added and the mixture was stirred at room temperature for 10 min. (R)-Isoserine ethyl ester hydrochloride (0.10 g, 0.6 mmol) and N,N-diisopropylethylamine (130 μL) dissolved in DMF (2.5 mL) were added and the resulting mixture was stirred at room temperature for 16 hours. The mixture was added ethyl acetate (70 mL) and washed with water (2×100 mL), the organic phase was dried with sodium sulphate and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with a mixture of ethyl acetate:n-heptane (1:2) containing 10% acetic acid. This afforded 100 mg of (R)-3-{4-[3-(3-bromophenyl)-1-(4-cyclohexylphenyl)ureidomethyl]benzoylamino}-2-hydroxypropionic acid ethyl ester. HPLC-MS (Method B): m/z=624 (M+1); Rt=5.33 min.

Workup

  1. additionwere added
  2. washwashed with water (2×100 mL)
  3. dry with materialthe organic phase was dried with sodium sulphate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography on silica gel eluting with a mixture of ethyl acetate:n-heptane (1:2)
  6. additioncontaining 10% acetic acid

Sources & evidence

ORD record
ord-6ee439e2eced467384c1dbc71b34cbb6
Source dataset
uspto-grants-2005_10
Patent number
US06953812B2

Reaction notes

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