Dichloromethane → HCID 178419806, compound

HRID 1887082Notes

Reaction equation

HRID 1887082 reaction equation
[N-:1]=[N+:2]=[N-:3].[Na+].[NH4+].[Cl-].C(OC([N:14]1[CH2:19][CH2:18][CH:17]([O:20][C:21]2[C:22]([C:31]#[N:32])=[C:23]3[C:28](=[CH:29][CH:30]=2)[CH:27]=[N:26][CH:25]=[CH:24]3)[CH2:16][CH2:15]1)=O)(C)(C)C.ClCCl>CN(C=O)C>[NH:14]1[CH2:19][CH2:18][CH:17]([O:20][C:21]2[C:22]([C:31]3[NH:32][N:3]=[N:2][N:1]=3)=[C:23]3[C:28](=[CH:29][CH:30]=2)[CH:27]=[N:26][CH:25]=[CH:24]3)[CH2:16][CH2:15]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 25517Ammonium Chloride2×HCID 33557Sodium AzideHCID 576468544-(5-Cyano-isoquinolin-6-yloxy)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 178419806HCID 178419806, compoundYield 13.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
160 °C

Procedure

Under argon atmosphere 78 mg (1.2 mmol) of NaN3 and 64 mg (1.2 mmol) of NH4Cl were added to a solution of 35 mg (0.1 mmol) 4-(5-Cyano-isoquinolin-6-yloxy)-piperidine-1-carboxylic acid tert-butyl ester (15) in 1 mL of DMF. The mixture was heated to approximately 160° C. and 7 bar pressure for 3 h in a microwave reactor (CEM Discovery). After cooling to room temperature aqueous NH4Cl-solution and dichloromethane was added. The mixture was filtered through a phase separation cartridge and the aqueous layer was washed twice with dichloromethane. The organic layers were combined and the solvents were distilled off. The remainder was subjected to preparative HPLC to yield 4 mg (8%) of compound 32 as trifluoroacetate. LCMS Method # 3, retention time 0.90 min, detected mass 297.04 [M+H]+

Workup

  1. additionwas added
  2. filtrationThe mixture was filtered through a phase separation cartridge
  3. washthe aqueous layer was washed twice with dichloromethane
  4. distillationthe solvents were distilled off

Sources & evidence

ORD record
ord-0290d0850b204ee3924367b902fbd12f
Source dataset
uspto-grants-2013_08
Patent number
US08501736B2

Reaction notes

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