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

HRID 967647노트

반응식

HRID 967647 반응식
[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

참가 물질

9

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-3779697e55bc46d894c261d878daf07c
출처 데이터셋
uspto-grants-2005_10
특허 번호
US06953812B2

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