Sodium Bicarbonate → 4-({1-[2-(4-cyanophenyl)ethyl]-4-hydroxypiperidin-4-ylmethyl}methylamino)-N-(tetrahydropyran-2-yloxy)benzamide

HRID 1727095ノート

反応式

HRID 1727095 の反応式
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][NH2:8].[C:9]([C:11]1[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][N:19]2[CH2:24][CH2:23][C:22]([CH2:26][N:27]([CH3:37])[C:28]3[CH:36]=[CH:35][C:31]([C:32](O)=[O:33])=[CH:30][CH:29]=3)([OH:25])[CH2:21][CH2:20]2)=[CH:13][CH:12]=1)#[N:10].Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.C(=O)([O-])O.[Na+]>CN(C)C=O.O>[C:9]([C:11]1[CH:12]=[CH:13][C:14]([CH2:17][CH2:18][N:19]2[CH2:20][CH2:21][C:22]([CH2:26][N:27]([CH3:37])[C:28]3[CH:36]=[CH:35][C:31]([C:32]([NH:8][O:7][CH:2]4[CH2:3][CH2:4][CH2:5][CH2:6][O:1]4)=[O:33])=[CH:30][CH:29]=3)([OH:25])[CH2:23][CH2:24]2)=[CH:15][CH:16]=1)#[N:10]

参加物

8

反応物 5

HCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 12986481UP9V9DB2RD

生成物 1

HCID 866033454-({1-[2-(4-cyanophenyl)ethyl]-4-hydroxypiperidin-4-ylmethyl}methylamino)-N-(tetrahydropyran-2-yloxy)benzamide収率 61.9%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒2 回

実験手順

A solution of O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (0.36 g) in anhydrous dimethylformamide (5 mL) was added dropwise to a solution of the compound (0.80 g) obtained in Example 1, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.47 g) and 1-hydroxybenzotriazole monohydrate (0.39 g) in anhydrous dimethylformamide (20 mL) under cooling with ice-water under nitrogen atmosphere, followed by stirring at the same temperature for twenty minutes and further stirring at room temperature for two days. After adding water, the mixture was treated with saturated aqueous sodium hydrogen carbonate solution to be adjusted to pH 8 and was extracted with ethyl acetate. The combined organic layer was sequentially washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, the residue was purified by silica gel column chromatography (eluent; ethyl acetate:methanol=4:1), was crystallized from ether to yield the titled compound (620 mg) as crystals.

後処理

  1. stirringfurther stirring at room temperature for two days
  2. extractionwas extracted with ethyl acetate
  3. washThe combined organic layer was sequentially washed with water and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was removed under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (eluent; ethyl acetate:methanol=4:1)
  7. customwas crystallized from ether

出典と根拠

ORDレコード
ord-713d2f67dcac45d287ecf15a9492fe24
出典データセット
uspto-grants-2009_02
特許番号
US07494987B2

反応ノート

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