Diisopropylethylamine → (E)-N-{(S)-2-[4-(4-Fluoro-benzoyl)-piperidin-1-yl]-1-hydroxymethyl-ethyl)-3-(5-cyano-2-methoxy-phenyl)-acrylamide

HRID 434304

Reaktionsgleichung

Reaktionsgleichung von HRID 434304
Cl.[NH2:2][C@H:3]([CH2:20][OH:21])[CH2:4][N:5]1[CH2:10][CH2:9][CH:8]([C:11]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)=[O:12])[CH2:7][CH2:6]1.C(N(C(C)C)CC)(C)C.[C:31]([C:33]1[CH:34]=[CH:35][C:36]([O:44][CH3:45])=[C:37](/[CH:39]=[CH:40]/[C:41](O)=[O:42])[CH:38]=1)#[N:32].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>ClCCl>[F:19][C:16]1[CH:15]=[CH:14][C:13]([C:11]([CH:8]2[CH2:7][CH2:6][N:5]([CH2:4][C@H:3]([NH:2][C:41](=[O:42])/[CH:40]=[CH:39]/[C:37]3[CH:38]=[C:33]([C:31]#[N:32])[CH:34]=[CH:35][C:36]=3[O:44][CH3:45])[CH2:20][OH:21])[CH2:10][CH2:9]2)=[O:12])=[CH:18][CH:17]=1

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 11458357(E)-3-(5-cyano-2-methoxy-phenyl)-acrylic acidHCID 68809497[1-((S)-2-Amino-3-hydroxy-propyl)-piperidin-4-yl]-(4-fluoro-phenyl)-methanone hydrochloride

Produkt 1

HCID 69986033(E)-N-{(S)-2-[4-(4-Fluoro-benzoyl)-piperidin-1-yl]-1-hydroxymethyl-ethyl)-3-(5-cyano-2-methoxy-phenyl)-acrylamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of [1-((S)-2-amino-3-hydroxy-propyl)-piperidin-4-yl]-(4-fluoro-phenyl)-methanone hydrochloride (1.8 g, 5.7 mmol) and diisopropylethylamine (2.0 ml, 11.4 mmol) in dichloromethane (45 ml) is added (E)-3-(5-cyano-2-methoxy-phenyl)-acrylic acid (1.1 g, 5.7 mmol) followed by 2-(1H benzotriazol-1-yl)-1,1,3,3,-tetramethyluronium tetrafluoroborate (1.83 g, 5.7 mmol). The reaction mixture is stirred at ambient temperature for 4.5 hours, then filtered and the filtrate washed with water (50 ml), saturated sodium bicarbonate solution (50 ml), water (50 ml) and brine (50 ml). The organic phase is dried over magnesium sulphate, the solvent evaporated and the residue purified by flash silica chromatography (dichloromethane:methanol; 98:2 to 92:8 elution gradient) to afford the product, [MH]+466.1.

Aufarbeitung

  1. filtrationfiltered
  2. washthe filtrate washed with water (50 ml), saturated sodium bicarbonate solution (50 ml), water (50 ml) and brine (50 ml)
  3. dry with materialThe organic phase is dried over magnesium sulphate
  4. customthe solvent evaporated
  5. customthe residue purified by flash silica chromatography (dichloromethane:methanol; 98:2 to 92:8 elution gradient)
  6. customto afford the product, [MH]+466.1

Quellen und Nachweise

ORD-Eintrag
ord-027795b7f3a748158af9e2b8b8b6ecbc
Quelldatensatz
uspto-grants-2003_12
Patentnummer
US06670379B2

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