Diisopropylethylamine → 3-{2-Ethyl-4-[5-(4-isobutyl-5-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-propionic acid

HRID 1676116ノート

反応式

HRID 1676116 の反応式
[CH2:1]([C:5]1[CH:6]=[C:7]([C:11]([OH:13])=O)[S:8][C:9]=1[CH3:10])[CH:2]([CH3:4])[CH3:3].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH2:45]([C:47]1[CH:52]=[C:51]([C:53](=[NH:56])[NH:54]O)[CH:50]=[C:49]([CH3:57])[C:48]=1[CH2:58][CH2:59][C:60]([OH:62])=[O:61])[CH3:46]>C(Cl)Cl>[CH2:45]([C:47]1[CH:52]=[C:51]([C:53]2[N:54]=[C:11]([C:7]3[S:8][C:9]([CH3:10])=[C:5]([CH2:1][CH:2]([CH3:3])[CH3:4])[CH:6]=3)[O:13][N:56]=2)[CH:50]=[C:49]([CH3:57])[C:48]=1[CH2:58][CH2:59][C:60]([OH:62])=[O:61])[CH3:46]

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 594978744-Isobutyl-5-methylthiophene-2-carboxylic acidHCID 178436623HCID 178436623、化合物

生成物 1

HCID 594978783-{2-Ethyl-4-[5-(4-isobutyl-5-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-propionic acid収率 15.6%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of 4-isobutyl-5-methyl-thiophene-2-carboxylic acid (126 mg, 637 μmol) in DCM (5 mL), DIPEA (249 mg, 1.93 mmol) is added followed TBTU (202 mg, 628 μmol). The mixture is stirred at rt for 30 min before 3-[2-ethyl-4-(N-hydroxycarbamimidoyl)-6-methyl-phenyl]-propionic acid (159 mg, 637 μmol) is added. The mixture is stirred at rt for 16 h before it is diluted with DCM, washed with 1 N aq. HCl solution, dried over Na2SO4, filtered and concentrated. The residue is dissolved in toluene (20 mL) and the reaction mixture is stirred at 110° C. for 18 h. The solvent is evaporated and the crude product is purified by CC on silica gel eluting with DCM containing 5% of methanol to give 3-{2-ethyl-4-[5-(4-isobutyl-5-methyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenyl}-propionic acid (41 mg) as a beige solid; LC-MS: tR=1.17 min, [M+1]+=413.30; 1H NMR (CDCl3): δ 0.94 (d, J=6.4 Hz, 6H), 1.30 (t, J=7.6 Hz, 3H), 1.84-1.96 (m, 1H), 2.43 (s, 3H), 2.45 (s, 3H), 2.46-2.60 (m, 4H), 2.75 (q, J=7.3 Hz, 2H), 3.02-3.12 (m, 2H), 7.66 (s, 1H), 7.79 (s, 1H), 7.81 (s, 1H).

後処理

  1. additionis added
  2. washwashed with 1 N aq. HCl solution
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe residue is dissolved in toluene (20 mL)
  7. stirringthe reaction mixture is stirred at 110° C. for 18 h
  8. customThe solvent is evaporated
  9. customthe crude product is purified by CC on silica gel eluting with DCM containing 5% of methanol

出典と根拠

ORDレコード
ord-1248438485bb46a09e9892942582811a
出典データセット
uspto-grants-2011_08
特許番号
US08003800B2

反応ノート

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