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

HRID 470912노트

반응식

HRID 470912 반응식
[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

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 68546596N'-((2R,3S)-2-(3-chloro-7-cyanobenzo[b]thiophen-4-ylamino)-3-hydroxybutanoyl)-4-cyanobenzohydrazide

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-018a50e666064f1289ea914aa3fec175
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08629167B2

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