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

HRID 1727095노트

반응식

HRID 1727095 반응식
[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]

참가 물질

8

반응물 5

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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매2회

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-713d2f67dcac45d287ecf15a9492fe24
출처 데이터셋
uspto-grants-2009_02
특허 번호
US07494987B2

반응 노트

불러오는 중…