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1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (S)-2-(benzyloxy)-N'-(4-(4-chlorophenyl)-5-(4-cyanophenyl)-1-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-6-oxo-1,6-dihydropyridazin-3-yl)propanehydrazide

HRID 1661109
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1661109
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([NH:14][NH2:15])=[N:12][N:11]([CH2:16][C:17]3[C:18]([CH3:27])=[N:19][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:21][CH:22]=3)[C:10](=[O:28])[C:9]=2[C:29]2[CH:36]=[CH:35][C:32]([C:33]#[N:34])=[CH:31][CH:30]=2)=[CH:4][CH:3]=1.[CH2:37]([O:44][C@@H:45]([CH3:49])[C:46](O)=[O:47])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>CCOC(C)=O.C1COCC1>[CH2:37]([O:44][C@@H:45]([CH3:49])[C:46]([NH:15][NH:14][C:13]1[C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)=[C:9]([C:29]2[CH:30]=[CH:31][C:32]([C:33]#[N:34])=[CH:35][CH:36]=2)[C:10](=[O:28])[N:11]([CH2:16][C:17]2[C:18]([CH3:27])=[N:19][C:20]([C:23]([F:25])([F:26])[F:24])=[CH:21][CH:22]=2)[N:12]=1)=[O:47])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1
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Komponenten

8

Edukt 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 11298298(S)-2-(benzyloxy)propanoic acidHCID 671287294-(5-(4-Chlorophenyl)-6-hydrazinyl-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-3-oxo-2,3-dihydropyridazin-4-yl)benzonitrile

Produkt 1

HCID 67129291
(S)-2-(benzyloxy)-N'-(4-(4-chlorophenyl)-5-(4-cyanophenyl)-1-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-6-oxo-1,6-dihydropyridazin-3-yl)propanehydrazide
Ausbeute 76,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a round bottom flask was added 4-(5-(4-chlorophenyl)-6-hydrazinyl-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-3-oxo-2,3-dihydropyridazin-4-yl)benzonitrile (70 mg, 0.1367 mmol), prepared as described in Example 2B, (S)-2-(benzyloxy)propanoic acid (25 mg, 0.1367 mmol), EDAC (30 mg, 0.15 mmol), HOBT (20.3 mg, 0.15 0 mmol), THF (5 ml) and diisopropyl ethyl amine (19.4 mg, 0.15 mmol). The reaction was stirred at rt for 5 hr. After this time, the reaction was diluted with EtOAc (40 ml). The resulting solution was extracted with water (2×20 ml), and saturated NaCl (20 ml). The organic layer was dried over MgSO4, filtered and concentrated. The crude product was purified by silica gel column chromatography (4 g silica gel) eluting with a gradient of 0%-60% EtOAc/Hex to give product (S)-2-(benzyloxy)-N′-(4-(4-chlorophenyl)-5-(4-cyanophenyl)-1-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-6-oxo-1,6-dihydropyridazin-3-yl)propanehydrazide as a beige solid (70 mg, 76% yield).

Aufarbeitung

  1. customprepared
  2. extractionThe resulting solution was extracted with water (2×20 ml), and saturated NaCl (20 ml)
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by silica gel column chromatography (4 g silica gel)
  7. washeluting with a gradient of 0%-60% EtOAc/Hex

Quellen und Nachweise

ORD-Eintrag
ord-9e6e136347c2418a9dc409c14a576c78
Quelldatensatz
uspto-grants-2011_10
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08030306B2

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