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 1676116노트

반응식

HRID 1676116 반응식
[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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-1248438485bb46a09e9892942582811a
출처 데이터셋
uspto-grants-2011_08
특허 번호
US08003800B2

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