Methyl 4-oxobutyrate → 4-[(R)-2-{3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-5-[4-(5-trifluoromethyl-furan-2-ylmethyl)-piperazin-1-yl]-3,6-dihydro-2H-pyrimidin-1-yl}-1-(2-hydroxy-phenyl)-ethylamino]-butyric acid methyl ester

HRID 574259

Reaktionsgleichung

Reaktionsgleichung von HRID 574259
[NH2:1][C@H:2]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=1[OH:47])[CH2:3][N:4]1[C:9](=[O:10])[C:8]([N:11]2[CH2:16][CH2:15][N:14]([CH2:17][C:18]3[O:19][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:21][CH:22]=3)[CH2:13][CH2:12]2)=[C:7]([CH3:27])[N:6]([CH2:28][C:29]2[C:34]([C:35]([F:38])([F:37])[F:36])=[CH:33][CH:32]=[CH:31][C:30]=2[F:39])[C:5]1=[O:40].[CH3:48][O:49][C:50](=[O:55])[CH2:51][CH2:52][CH:53]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>>[CH3:48][O:49][C:50](=[O:55])[CH2:51][CH2:52][CH2:53][NH:1][C@H:2]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=1[OH:47])[CH2:3][N:4]1[C:9](=[O:10])[C:8]([N:11]2[CH2:16][CH2:15][N:14]([CH2:17][C:18]3[O:19][C:20]([C:23]([F:25])([F:24])[F:26])=[CH:21][CH:22]=3)[CH2:13][CH2:12]2)=[C:7]([CH3:27])[N:6]([CH2:28][C:29]2[C:34]([C:35]([F:38])([F:36])[F:37])=[CH:33][CH:32]=[CH:31][C:30]=2[F:39])[C:5]1=[O:40]

Komponenten

5

Edukt 4

HCID 83779Methyl 4-oxobutyrateHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 872853823-[(R)-2-amino-2-(2-hydroxy-phenyl)-ethyl]-1-(2-fluoro-6-trifluoromethyl-benzyl)-6-methyl-5-[4-(5-trifluoromethyl-furan-2-ylmethyl)-piperazin-1-yl]-1H-pyrimidine-2,4-dione

Produkt 1

HCID 872855474-[(R)-2-{3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-5-[4-(5-trifluoromethyl-furan-2-ylmethyl)-piperazin-1-yl]-3,6-dihydro-2H-pyrimidin-1-yl}-1-(2-hydroxy-phenyl)-ethylamino]-butyric acid methyl esterAusbeute 53 %

Versuchsvorschrift

To a solution of 3-[(R)-2-amino-2-(2-hydroxy-phenyl)-ethyl]-1-(2-fluoro-6-trifluoromethyl-benzyl)-6-methyl-5-[4-(5-trifluoromethyl-furan-2-ylmethyl)-piperazin-1-yl]-1H-pyrimidine-2,4-dione (15-1) (67 mg, 0.100 mmol) in 1,2-dicholoroethane (2 mL) were 4-oxo-butyric acid methyl ester (17 mg, 0.150 mmol) and sodium triacetoxyborohydride (42 mg, 0.200 mmol) in the order, followed by stirring at room temperature for 1.5 hrs. The solution was neutralized with an aqueous saturated sodium bicarbonate solution to separate an organic layer. After concentration of the organic layer, the residue was purified using silica gel chromatography(eluent: dichloromethane/methanol, 30/1) and dried in a vacuum to afford 40 mg of the compound as a colorless oil (yield 53%). 1H NMR (300 MHz, CDCl3) δ 1.79 (2H, m), 2.20-2.33 (4H, m), 2.32 (3H, s), 2.48 (2H, m), 2.60 (2H, t), 2.80 (2H, m), 3.58 (2H, m), 3.61 (2H, s), 3.63 (3H, s), 4.06-4.15 (2H, m), 4.42 (1H, dd), 5.42 (2H, dd), 6.30 (1H, d), 6.72-6.78 (3H, m), 7.06-7.15 (2H, m), 7.26 (1H, m), 7.41 (1H, m), 7.55 (1H, d)

Aufarbeitung

  1. customto separate an organic layer
  2. customAfter concentration of the organic layer, the residue was purified
  3. dry with materialdichloromethane/methanol, 30/1) and dried in a vacuum

Quellen und Nachweise

ORD-Eintrag
ord-38a6be038dec47a8aa0e6bec4a726cb2
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09034850B2

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