2-Phenylpropionic acid → N-(2-{1-[2-(2,5-dimethyl-phenyl)-acetyl]-piperidin-4-yl}-thiazol-4-yl)-2-phenyl-propionamide

HRID 1042059Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1042059
[C:1]1([CH:7]([CH3:11])[C:8]([OH:10])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[NH2:48][C:49]1[N:50]=[C:51]([CH:54]2[CH2:59][CH2:58][N:57]([C:60](=[O:70])[CH2:61][C:62]3[CH:67]=[C:66]([CH3:68])[CH:65]=[CH:64][C:63]=3[CH3:69])[CH2:56][CH2:55]2)[S:52][CH:53]=1>C(#N)C>[CH3:69][C:63]1[CH:64]=[CH:65][C:66]([CH3:68])=[CH:67][C:62]=1[CH2:61][C:60]([N:57]1[CH2:56][CH2:55][CH:54]([C:51]2[S:52][CH:53]=[C:49]([NH:48][C:8](=[O:10])[CH:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH3:11])[N:50]=2)[CH2:59][CH2:58]1)=[O:70]

Komponenten

6

Edukt 4

HCID 102962-Phenylpropionic acidHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 669555241-[4-(4-Amino-thiazol-2-yl)-piperidin-1-yl]-2-(2,5-dimethyl-phenyl)-ethanone

Produkt 1

HCID 66956445N-(2-{1-[2-(2,5-dimethyl-phenyl)-acetyl]-piperidin-4-yl}-thiazol-4-yl)-2-phenyl-propionamideAusbeute 13,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

To a solution of (rac.)-2-phenylpropionic acid (46 mg, 0.30 mmol) and diisopropylethylamine (0.15 mL, 0.9 mmol) in acetonitrile (2 mL) is added benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (322 mg, 0.73 mmol) at RT. After stirring 30 min at RT, 1-[4-(4-amino-thiazol-2-yl)-piperidin-1-yl]-2-(2,5-dimethyl-phenyl)-ethanone (100 mg, 0.30 mmol) is added to the reaction mixture. After stirring overnight at RT, the solvent is evaporated and the residue is purified by flash chromatography on silica gel (ethylacetate/cyclohexane 1:1) to give N-(2-{1-[2-(2,5-dimethyl-phenyl)-acetyl]-piperidin-4-yl}-thiazol-4-yl)-2-phenyl-propionamide (Compound No. I.g.141, 19 mg, 13.4%). 1H-NMR (400 MHz, CDCl3): δ=1.46-1.39 (m, 1H), 1.52 (d, 3H), 1.68-1.56 (m, 1H), 1.89-1.83 (m, 1H), 2.01-1.97 (m, 1H), 2.15 (s, 3H), 2.19 (s, 3H), 2.73-2.67 (m, 1H), 3.18-2.92 (m, 2H), 3.59 (s, 2H), 3.68-3.63 (q, 1H), 3.78-3.71 (m, 1H), 4.65-4.62 (m, 1H), 6.91-6.82 (m, 2H), 7.02-6.98 (m, 1H), 7.31-7.15 (m, 5H), 7.42 (s, 1H), 8.05 (br, 1H). MS: m/z=462 (M+1).

Aufarbeitung

  1. stirringAfter stirring overnight at RT
  2. customthe solvent is evaporated
  3. customthe residue is purified by flash chromatography on silica gel (ethylacetate/cyclohexane 1:1)

Quellen und Nachweise

ORD-Eintrag
ord-05cd72285c7b4eb6b7440034de06883b
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08557821B2

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