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

HRID 1727095Notes

Reaction equation

HRID 1727095 reaction equation
[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]

Participants

8

Reactant 5

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-713d2f67dcac45d287ecf15a9492fe24
Source dataset
uspto-grants-2009_02
Patent number
US07494987B2

Reaction notes

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