Sodium hydride → HCID 59805853, compound

HRID 1429664Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[N:4][C:3]=1[NH2:12].[H-].[Na+].[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25](OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:10])([F:9])[F:11])[N:5]=[N:4][C:3]=1[NH:12][CH:25]1[CH2:26][CH2:27][N:22]([C:20]([O:19][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:21])[CH2:23][CH2:24]1

Participants

Conditions

Temperature: 85 °C

Procedure

To a stirred solution of D7 (1.6 g, 8.1 mmol) in dimethylformamide (50 ml) at 0° C., under nitrogen, was added NaH (60% in oil; 390 mg, 8.1 mmol) portionwise. The reaction mixture was stirred for 1 h, before 4-(toluene-4-sulfonyloxy)-piperidine-1-carboxylic acid tert-butyl ester (2.9 g, 8.1 mmol), dissolved in dimethylformamide (10 ml), was added dropwise. The reaction mixture was then heated between 80-90° C. for 6 hours. After cooling to room temperature, the solvents were evaporated in vacuo. The residue was dissolved in dichloromethane and washed with water. The organic layer was dried (MgSO4), filtered and the solvents were evaporated in vacuo. The crude product was purified by column chromatography (silica gel; 3% methanol in dichloromethane) to give D8 (1.1 g, 37%). C15H20ClF3N4O2 requires 380; Found 381 (MH+).

Workup

additionwas added dropwise
temperatureAfter cooling to room temperature
customthe solvents were evaporated in vacuo
dissolutionThe residue was dissolved in dichloromethane
washwashed with water
dry with materialThe organic layer was dried (MgSO4)
filtrationfiltered
customthe solvents were evaporated in vacuo
customThe crude product was purified by column chromatography (silica gel; 3% methanol in dichloromethane)

Sources & evidence

ORD record: ord-598af628c1884d0ab90cc477849a6af3
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08940743B2

Reaction notes

Loading…