Water → N,N'-Di-tert-Butoxycarbonyl-7-[1-(pyridin-4-ylmethyl)piperidin-4-ylmethoxy]-1,2,3,4-tetrahydroisoquinoline-2-carboxamidine

HRID 412563Notes

Reaction equation

HRID 412563 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([N:18]1[CH2:27][CH2:26][C:25]2[C:20](=[CH:21][C:22]([O:28][CH2:29][CH:30]3[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]3)=[CH:23][CH:24]=2)[CH2:19]1)=[N:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].Cl.[N:39]1[CH:44]=[CH:43][C:42]([CH2:45]Cl)=[CH:41][CH:40]=1.O>O1CCCC1.CN(C)C=O>[C:14]([O:13][C:11]([NH:10][C:9]([N:18]1[CH2:27][CH2:26][C:25]2[C:20](=[CH:21][C:22]([O:28][CH2:29][CH:30]3[CH2:35][CH2:34][N:33]([CH2:45][C:42]4[CH:43]=[CH:44][N:39]=[CH:40][CH:41]=4)[CH2:32][CH2:31]3)=[CH:23][CH:24]=2)[CH2:19]1)=[N:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[O:12])([CH3:17])([CH3:16])[CH3:15]

Participants

7

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 745704-(Chloromethyl)pyridinium chlorideHCID 60064218N,N'-ditert-butoxycarbonyl-7-(piperidin-4-ylmethoxy)-1,2,3,4-tetrahydroisoquinoline-2-carboxamidine

Product 1

HCID 69697137N,N'-Di-tert-Butoxycarbonyl-7-[1-(pyridin-4-ylmethyl)piperidin-4-ylmethoxy]-1,2,3,4-tetrahydroisoquinoline-2-carboxamidineYield 78.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of N,N′-di-tert-butoxycarbonyl-7-(piperidin-4-ylmethoxy)-1,2,3,4-tetrahydroisoquinoline-2-carboxamidine (100 mg) in a mixture of tetrahydrofuran (1 ml) and dimethylformamide (1 ml) were added 9.1N sodium hydroxide (0.068 ml) and 4-picolyl chloride hydrochloride (51 mg), and the mixture was stirred at 50° C. for 5 hours. After completion of the reaction, water was added and the mixture was extracted with ethyl acetate and was washed successively with water and saturated brine. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated. The obtained residue was purified by preparative thin layer chromatography (chloroform:methanol=20:1) and dried under reduced pressure to give the title compound (93 mg).

Workup

  1. additionwas added
  2. extractionthe mixture was extracted with ethyl acetate
  3. washwas washed successively with water and saturated brine
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. customthe solvent was evaporated
  6. customThe obtained residue was purified by preparative thin layer chromatography (chloroform:methanol=20:1)
  7. customdried under reduced pressure

Sources & evidence

ORD record
ord-da003b75361c4e87a060f889e10d4c8e
Source dataset
uspto-grants-2003_05
Patent number
US06562828B1

Reaction notes

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