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1-Hydroxybenzotriazole → 3-[3-(3-Methyl-1-{2-[4-(3-o-tolyl-ureido)-phenyl]-acetylamino}-butyl)-isoxazol-5-yl]-propionic acid methyl ester

HRID 381514
ノート
印刷プレビュー

反応式

HRID 381514 の反応式
[C:1]1([CH3:21])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8](=[O:20])[NH:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][C:17]([OH:19])=O)=[CH:12][CH:11]=1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Br.[CH3:54][O:55][C:56](=[O:70])[CH2:57][CH2:58][C:59]1[O:63][N:62]=[C:61]([CH:64]([NH2:69])[CH2:65][CH:66]([CH3:68])[CH3:67])[CH:60]=1>C(Cl)Cl.O>[CH3:54][O:55][C:56](=[O:70])[CH2:57][CH2:58][C:59]1[O:63][N:62]=[C:61]([CH:64]([NH:69][C:17](=[O:19])[CH2:16][C:13]2[CH:12]=[CH:11][C:10]([NH:9][C:8]([NH:7][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=3[CH3:21])=[O:20])=[CH:15][CH:14]=2)[CH2:65][CH:66]([CH3:68])[CH3:67])[CH:60]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66052544-((((2-Methylphenyl)amino)carbonyl)amino)benzeneacetic acidHCID 696929213-[3-(1-Amino-3-methyl-butyl)-isoxazol-5-yl]-propionic acid methyl ester hydrobromide

生成物 1

HCID 18682368
3-[3-(3-Methyl-1-{2-[4-(3-o-tolyl-ureido)-phenyl]-acetylamino}-butyl)-isoxazol-5-yl]-propionic acid methyl ester
収率 51.1%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒3 回

実験手順

To a stirred solution of [4-(3-o-tolyl-ureido)-phenyl]-acetic acid (305 mg, 1.07 mmol), DIEA (1.3 ml), HOBT (120 mg, 0.89 mmol) and EDCl (170 mg, 0.89 mmol) in CH2Cl2 (8 ml) at room temperature was added a solution of 3-[3-(1-amino-3-methyl-butyl)-isoxazol-5-yl]-propionic acid methyl ester hydrobromide (272 mg, 0.85 mmol) in CH2Cl2 (12 ml). After stirring for 16 h at room temperature the mixture was diluted with CH2Cl2 (20 ml) and poured into water. The layers were separated and the aqueous layer was extracted with CH2Cl2 (20 ml×3). The combined organics were dried over MgSO4; filtered; and concentrated under reduced pressure. The residue was purified by Flash 40 chromatography using a silica gel column and eluting with 65% EtOAc/hexane to give 220 mg of the title compound as a white amorphous solid. MP 153-4° C.; MS [M+ 1]+507.2; 1H nmr (400 MHz, CDCl3) δ0.88 (d, J=6.4 Hz, 6H), 1.53-1.66 (m, 3H), 2.21 (s, 3H), 2.66 (t, J=7.6 Hz, 2H), 3.00 (t, J=7.6 Hz, 2H), 3.49 (s, 2H), 3.68 (s, 3H), 5.15 (dt, J=6.2 and 8.7 Hz, 1H), 5.85 (s, 1H), 6.11 (d, J=8.5 Hz, 1H), 6.65 (s, 1H), 7.00 (s, 1H), 7.05-7.24 (m, 7H), 7.53 (d, 1H); Anal. calcd. for C28H34N4O5: C (66.39), H (6.76), N (11.05). Found: C (66.29), H (7.11), N (11.11).

後処理

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with CH2Cl2 (20 ml×3)
  3. dry with materialThe combined organics were dried over MgSO4
  4. filtrationfiltered
  5. concentrationand concentrated under reduced pressure
  6. customThe residue was purified by Flash 40 chromatography
  7. washeluting with 65% EtOAc/hexane

出典と根拠

ORDレコード
ord-0d53ac1c26c54a43bcf60910858991fd
出典データセット
uspto-grants-2001_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US06306887B1

反応ノート

読み込み中…

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