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

HRID 563321ノート

反応式

HRID 563321 の反応式
[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

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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, J=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).

後処理

  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

出典と根拠

ORDレコード
ord-67fd67bb4c3d4ddd9474d964843d075e
出典データセット
uspto-grants-2011_11
特許番号
US08067448B2

反応ノート

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