Diisopropylethylamine → 4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-{(1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-[(4-fluorophenyl)methyl]ethyl}-5-methyl-2-furancarboxamide

HRID 1961246Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1961246
[Cl:1][C:2]1[CH:3]=[N:4][N:5]([CH3:16])[C:6]=1[C:7]1[CH:8]=[C:9]([C:13]([OH:15])=O)[O:10][C:11]=1[CH3:12].[NH2:17][C@@H:18]([CH2:31][C:32]1[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=1)[CH2:19][N:20]1[C:28](=[O:29])[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21]1=[O:30].CC(OC(N[C@H](C(O)=O)CC1C=CC=CC=1C(F)(F)F)=O)(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:3]=[N:4][N:5]([CH3:16])[C:6]=1[C:7]1[CH:8]=[C:9]([C:13]([NH:17][C@@H:18]([CH2:31][C:32]2[CH:33]=[CH:34][C:35]([F:38])=[CH:36][CH:37]=2)[CH2:19][N:20]2[C:28](=[O:29])[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:21]2=[O:30])=[O:15])[O:10][C:11]=1[CH3:12]

Komponenten

7

Edukt 5

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 2761473Boc-2-(trifluoromethyl)-L-phenylalanineHCID 578264484-(4-chloro-1-methyl-1H-pyrazol-5-yl)-5-methyl-2-furancarboxylic acidHCID 670661152-[(2S)-2-amino-3-(4-fluorophenyl)propyl]-1H-isoindole-1,3(2H)-dione

Produkt 1

HCID 578267684-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-{(1S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-[(4-fluorophenyl)methyl]ethyl}-5-methyl-2-furancarboxamideAusbeute 67 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6212ChloroformLösungsmittel

Versuchsvorschrift

To a 50 mL round-bottomed flask was added 4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-5-methyl-2-furancarboxylic acid (248 mg, 0.97 mmol) [prepared according to the procedure of Example 184], 2-[(2S)-2-amino-3-(4-fluorophenyl)propyl]-1H-isoindole-1,3(2H)-dione (321 mg, 0.96 mmol) [prepared according to the procedure of Preparation 6, except substituting N-{[(1,1-dimethylethyl)oxy]carbonyl}-4-fluoro-L-phenylalanine (4.95 g, 17.5 mmol) for N-{[(1,1-dimethylethyl)oxy]carbonyl}-2-(trifluoromethyl)-L-phenylalanine] and PyBrop (557 mg, 1.19 mmol) in chloroform (9.5 mL). DIEA (840 μL, 4.81 mmol) was added and the reaction stirred overnight at room temperature. The mixture was adsorbed onto silica and purified via column chromatography (25-70% EtOAc/Hex) affording the title compound (167 mg, 0.26 mmol, 67%): LC-MS (ES) m/z=521 (M+H)+.

Aufarbeitung

  1. customprepared
  2. customprepared
  3. customaccording to the procedure of Preparation 6
  4. custompurified via column chromatography (25-70% EtOAc/Hex)

Quellen und Nachweise

ORD-Eintrag
ord-4352c66cfb95408a9d8798d64bbd20ff
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08410158B2

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