Methanol → 4-((1R,2S)-2-hydroxy-1-(5-phenyl-1,3,4-oxadiazol-2-yl)propylamino)benzo[b]thiophene-7-carbonitrile

HRID 470861노트

반응식

HRID 470861 반응식
[C:1]([C:3]1[C:8]2[S:9][CH:10]=[CH:11][C:7]=2[C:6]([NH:12][C@H:13]([C@@H:26]([OH:28])[CH3:27])[C:14]([NH:16][NH:17][C:18](=O)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:15])=[CH:5][CH:4]=1)#[N:2].CCN(P1(N(C)CCCN1C)=NC(C)(C)C)CC.CO>C1COCC1>[OH:28][C@@H:26]([CH3:27])[C@@H:13]([NH:12][C:6]1[C:7]2[CH:11]=[CH:10][S:9][C:8]=2[C:3]([C:1]#[N:2])=[CH:4][CH:5]=1)[C:14]1[O:15][C:18]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[N:17][N:16]=1

참가 물질

5

반응물 3

HCID 887MethanolHCID 35138512-((1,1-Dimethylethyl)imino)-N,N-diethylhexahydro-1,3-dimethyl-2lambda5-1,3,2-diazaphosphorin-2-amineHCID 67006447N'-((2R,3S)-2-(7-cyanobenzo[b]thiophen-4-ylamino)-3-hydroxybutanoyl)benzohydrazide

생성물 1

HCID 670064574-((1R,2S)-2-hydroxy-1-(5-phenyl-1,3,4-oxadiazol-2-yl)propylamino)benzo[b]thiophene-7-carbonitrile수율 25.4%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of N′-((2R,3S)-2-(7-cyanobenzo[b]thiophen-4-ylamino)-3-hydroxybutanoyl)benzohydrazide (0.69 g, 1.75 mmol) in THF (100 mL) were added PS-BEMP (2.39 g, 5.27 mmol, ˜2.2 mmol/g) and p-TsCl (353 mg, 1.85 mmol) at room temperature. The mixture was stirred at room temperature for 14 h, then methanol (5 mL) was added to quench the reaction. The resin was filtered and washed with MeOH. The combined filtrate was concentrated to give a residue, which was purified by flash chromatography to afford the title compound 4-((1R,2S)-2-hydroxy-1-(5-phenyl-1,3,4-oxadiazol-2-yl)propylamino)benzo[b]thiophene-7-carbonitrile (167 mg, 25%) as a foam and the dehydration product 4-(1-(5-phenyl-1,3,4-oxadiazol-2-yl)prop-1-enylamino)benzo[b]thiophene-7-carbonitrile (33 mg, 5%). Title compound: 1H NMR (400 MHz, Acetone-d6, δ in ppm) 7.98 (m, 2H), 7.88 (d, J=5.7 Hz, 1H), 7.72 (d, 5.7 Hz, 1H), 7.63 (d, J=8.2 Hz, 1H), 7.51˜7.57 (m, 3H), 6.85 (d, J=8.2 Hz, 1H), 6.50 (d, J=8.4 Hz, 1H), 5.22 (dd, J=4.7, 8.4 Hz, 1H), 4.80 (b, 1H), 4.65 (m, 1H), 1.42 (d, J=6.4 Hz, 3H). Dehydration product: 1H NMR (400 MHz, Acetone-d6, δ in ppm) 8.05 (m, 2H), 7.95 (d, J=5.6 Hz, 1H), 7.78 (d, J=5.6 Hz, 1H), 7.55˜7.62 (m, 4H), 7.01 (q, J=7.1 Hz, 1H), 6.57 (d, J=8.4 Hz, 1H), 1.93 (d, J=7.1 Hz, 3H).

후처리

  1. customto quench
  2. customthe reaction
  3. filtrationThe resin was filtered
  4. washwashed with MeOH
  5. concentrationThe combined filtrate was concentrated
  6. customto give a residue, which
  7. customwas purified by flash chromatography

출처 및 근거

ORD 기록
ord-a3c01f51ffea482a8b8a6c2bfefd148e
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08629167B2

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