Water → Ethyl 4-(2-{(3,5-bis-trifluoromethyl-benzyl)-[2-(6-chloro-pyrimidin-4-yloxy)-5-trifluoromethyl-benzyl]-amino}-pyrimidin-5-yloxy)-butyrate

HRID 604133ノート

反応式

HRID 604133 の反応式
[F:1][C:2]([F:43])([F:42])[C:3]1[CH:4]=[C:5]([CH:35]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:37]=1)[CH2:6][N:7]([CH2:23][C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=1[OH:34])[C:8]1[N:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:10][N:9]=1.[H-].[Na+].[Cl:46][C:47]1[CH:52]=[C:51](Cl)[N:50]=[CH:49][N:48]=1.O>CN(C)C=O.C(OCC)(=O)C>[F:43][C:2]([F:1])([F:42])[C:3]1[CH:4]=[C:5]([CH:35]=[C:36]([C:38]([F:39])([F:40])[F:41])[CH:37]=1)[CH2:6][N:7]([CH2:23][C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=1[O:34][C:51]1[CH:52]=[C:47]([Cl:46])[N:48]=[CH:49][N:50]=1)[C:8]1[N:9]=[CH:10][C:11]([O:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:12][N:13]=1

参加物

7

反応物 4

HCID 962WaterHCID 24758Sodium hydrideHCID 709434,6-Dichloropyrimidine2 回HCID 86626825Ethyl 4-{2-[(3,5-bis-trifluoromethyl-benzyl)-(2-hydroxy-5-trifluoromethyl-benzyl)-amino]-pyrimidin-5-yloxy}-butyrate

生成物 1

HCID 86626879Ethyl 4-(2-{(3,5-bis-trifluoromethyl-benzyl)-[2-(6-chloro-pyrimidin-4-yloxy)-5-trifluoromethyl-benzyl]-amino}-pyrimidin-5-yloxy)-butyrate収率 68.9%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

Ethyl 4-{2-[(3,5-bis-trifluoromethyl-benzyl)-(2-hydroxy-5-trifluoromethyl-benzyl)-amino]-pyrimidin-5-yloxy}-butyrate (300 mg) is dissolved in N,N-dimethylformamide (5 ml) and thereto are added sodium hydride (60%) (29 mg) and 4,6-dichloro-pyrimidine (107 mg) under ice-cooling, and the mixture is stirred for 30 minutes, and the reaction solution is cooled to room temperature, and thereto is added 4,6-dichloro-pyrimidine (107 mg), and the mixture is stirred for 30 minutes. To the reaction solution are added water and ethyl acetate, and the mixture is separated, and the organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=49:1→17:1) to give ethyl 4-(2-{(3,5-bis-trifluoromethyl-benzyl)-[2-(6-chloro-pyrimidin-4-yloxy)-5-trifluoromethyl-benzyl]-amino}-pyrimidin-5-yloxy)-butyrate (244 mg). MS (m/z): 738/740 [M+H]+

後処理

  1. temperaturecooling
  2. stirringthe mixture is stirred for 30 minutes
  3. customthe mixture is separated
  4. washthe organic layer is washed with a saturated brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=49:1→17:1)

出典と根拠

ORDレコード
ord-c736762d4e974696ac5828d6c6588203
出典データセット
uspto-grants-2011_03
特許番号
US07906517B2

反応ノート

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