Diisopropylethylamine → 3-cyano-N-[(2S)-2-(4-fluorophenyl)pent-4-en-1-yl]-N-methyl-5,6,7,8-tetrahydronaphthalene-1-carboxamide

HRID 749450Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 749450
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([CH2:12][CH:13]=[CH2:14])[CH2:9][NH:10][CH3:11])=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[C:24]([C:26]1[CH:27]=[C:28]([C:36](Cl)=[O:37])[C:29]2[CH2:30][CH2:31][CH2:32][CH2:33][C:34]=2[CH:35]=1)#[N:25]>C(Cl)Cl>[C:24]([C:26]1[CH:27]=[C:28]([C:36]([N:10]([CH2:9][C@H:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[CH2:12][CH:13]=[CH2:14])[CH3:11])=[O:37])[C:29]2[CH2:30][CH2:31][CH2:32][CH2:33][C:34]=2[CH:35]=1)#[N:25]

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 15536023[(2S)-2-(4-Fluorophenyl)pent-4-en-1-yl]methylamineHCID 224526673-Cyano-5,6,7,8-tetrahydronaphthalene-1-carbonyl chloride

Produkt 1

HCID 689785133-cyano-N-[(2S)-2-(4-fluorophenyl)pent-4-en-1-yl]-N-methyl-5,6,7,8-tetrahydronaphthalene-1-carboxamideAusbeute 78,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

[(2S)-2-(4-Fluorophenyl)pent-4-en-1-yl]methylamine (see Bioorg. Med. Chem. Lett; 2001; 265-270; 300 mg, 1.55 mmol) was dissolved in CH2Cl2 (30 m]L) and to the resultant solution were added DIPEA (440 mg, 3.40 mmol) together with 3-cyano-5,6,7,8-tetrahydronaphthalene-1-carbonyl chloride (see WO 00/34243; 341 mg, 1.55 mmol). The mixture was stirred for 2 h at room temperature, diluted with CH2Cl2 (20 mL) and then washed with water, aqueous KHSO4 solution and finally with brine. The solution was dried over Na2SO4 and then the solvent was evaporated. The residue was chromatographed on silica gel using a mixture of heptane and ethyl acetate as eluent (7:3) and there was obtained 460 mg (78%) of 3-cyano-N-[(2S)-2-(4-fluorophenyl)pent-4-en-1-yl]-N-methyl-5,6,7,8-tetrahydronaphthalene-1-carboxamide as an oil. 1H NMR (400 MHz, CDCl3): 0.8-4.2 (cm, 16H), 4.8-5.1 (m, 2H), 5.6-5.8 (m, 1H), 6.7-7.4 (cm, 6H); LCMS: m/z 377 (M+1)+.

Aufarbeitung

  1. washwashed with water, aqueous KHSO4 solution and finally with brine
  2. dry with materialThe solution was dried over Na2SO4
  3. customthe solvent was evaporated
  4. customThe residue was chromatographed on silica gel using
  5. additiona mixture of heptane and ethyl acetate as eluent (7:3)

Quellen und Nachweise

ORD-Eintrag
ord-82c5437a078b48b7a47678055bc0e6cb
Quelldatensatz
uspto-grants-2008_07
Patentnummer
US07402581B2

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