Methanol → 3-chloro-4-((1R,2S)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxypropylamino)benzo[b]thiophene-7-carbonitrile

HRID 470912ノート

反応式

HRID 470912 の反応式
[Cl:1][C:2]1[C:3]2[C:10]([NH:11][C@H:12]([C@@H:27]([OH:29])[CH3:28])[C:13]([NH:15][NH:16][C:17](=O)[C:18]3[CH:23]=[CH:22][C:21]([C:24]#[N:25])=[CH:20][CH:19]=3)=[O:14])=[CH:9][CH:8]=[C:7]([C:30]#[N:31])[C:4]=2[S:5][CH:6]=1.CCN(P1(N(C)CCCN1C)=NC(C)(C)C)CC.CO>C1COCC1>[Cl:1][C:2]1[C:3]2[C:10]([NH:11][C@@H:12]([C:13]3[O:14][C:17]([C:18]4[CH:19]=[CH:20][C:21]([C:24]#[N:25])=[CH:22][CH:23]=4)=[N:16][N:15]=3)[C@@H:27]([OH:29])[CH3:28])=[CH:9][CH:8]=[C:7]([C:30]#[N:31])[C:4]=2[S:5][CH:6]=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 68546596N'-((2R,3S)-2-(3-chloro-7-cyanobenzo[b]thiophen-4-ylamino)-3-hydroxybutanoyl)-4-cyanobenzohydrazide

生成物 1

HCID 685468493-chloro-4-((1R,2S)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxypropylamino)benzo[b]thiophene-7-carbonitrile収率 9.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of N′-((2R,3S)-2-(3-chloro-7-cyanobenzo[b]thiophen-4-ylamino)-3-hydroxybutanoyl)-4-cyanobenzohydrazide (0.83 g, 1.83 mmol) in THF (150 mL) was added PS-BEMP (2.5 g, 5.50 mmol, ˜2.2 mmol/g) and p-TsCl (383 mg, 2.00 mmol) at room temperature. The mixture was stirred at room temperature overnight, then methanol (5 mL) was added to quench the reaction. The resin was filtered and washed with MeOH (400 mL). The combined filtrate was concentrated to give a residue, which was purified by flash chromatography to afford the title compound 3-chloro-4-((1R,2S)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxypropylamino)benzo[b]thiophene-7-carbonitrile (75.2 mg, 9%). 1H NMR (400 MHz, Acetone-d6, δ in ppm) 8.20 (d, J=8.3 Hz, 2H), 8.00 (d, J=8.3 Hz, 2H), 7.75 (s, 1H), 7.68 (d, J=8.2 Hz, 1H), 7.65 (d, J=8.6 Hz, 1H), 6.81 (d, J=8.6 Hz, 1H), 5.28 (dd, J=2.4, 8.2 Hz, 1H), 4.93 (d, J=4.3 Hz, 1H), 4.72 (m, 1H), 1.50 (d, J=6.3 Hz, 3H).

後処理

  1. customto quench
  2. customthe reaction
  3. filtrationThe resin was filtered
  4. washwashed with MeOH (400 mL)
  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-018a50e666064f1289ea914aa3fec175
出典データセット
uspto-grants-2014_01
特許番号
US08629167B2

反応ノート

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