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

反応式

HRID 574259 の反応式
[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]

参加物

5

反応物 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

生成物 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 ester収率 53%

実験手順

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)

後処理

  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

出典と根拠

ORDレコード
ord-38a6be038dec47a8aa0e6bec4a726cb2
出典データセット
uspto-grants-2015_05
特許番号
US09034850B2

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