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

HRID 967647ノート

反応式

HRID 967647 の反応式
[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

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-3779697e55bc46d894c261d878daf07c
出典データセット
uspto-grants-2005_10
特許番号
US06953812B2

反応ノート

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