Cesium carbonate → tert-Butyl 1-(6-(4-cyanophenyl)-4,5-dimethylpyridazin-3-yl)piperidin-4-yl(methyl)carbamate

HRID 1890761Notes

Reaction equation

HRID 1890761 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]([CH3:22])[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:10][CH2:9]2)=[C:4]([CH3:23])[C:3]=1[CH3:24].[C:25]([C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1)#[N:26].C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O>[C:25]([C:27]1[CH:32]=[CH:31][C:30]([C:2]2[N:7]=[N:6][C:5]([N:8]3[CH2:13][CH2:12][CH:11]([N:14]([CH3:22])[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:10][CH2:9]3)=[C:4]([CH3:23])[C:3]=2[CH3:24])=[CH:29][CH:28]=1)#[N:26]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27343264-Cyanophenylboronic acidHCID 58486430HCID 58486430, compound

Product 1

HCID 58486412tert-Butyl 1-(6-(4-cyanophenyl)-4,5-dimethylpyridazin-3-yl)piperidin-4-yl(methyl)carbamateYield 94.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Heat a mixture of tert-butyl 1-(6-chloro-4,5-dimethylpyridazin-3-yl)piperidin-4-yl(methyl)carbamate (1.5 g, 4.23 mmol), 4-cyanophenylboronic acid (932 mg, 6.34 mmol), Cs2CO3 (5.51 g, 16.9 mmol) and (SP-4-1)-bis[bis(1,1-dimethylethyl)(4-methoxyphenyl)phosphine-κP]dichloro-palladium (29 mg, 0.042 mmol) in a mixture of 1,4-dioxane (30 mL) and H2O (10 mL) under N2 at 90° C. overnight. Partition the reaction mixture between EtOAc and H2O with dissolved NaHCO3. Separate the layers, and extract the aqueous layer with EtOAc. Combine the organic layers, dry over Na2SO4, filter, and concentrate under reduced pressure. Purify the residue by flash silica gel chromatography (gradient of 0 to 2% 2 M NH3/MeOH in CH2Cl2) to provide the title compound as a yellow solid (1.68 g, 94%). ES/MS m/z 422.2 (M+1).

Workup

  1. temperatureHeat
  2. customPartition the reaction mixture between EtOAc and H2O with dissolved NaHCO3
  3. customSeparate the layers
  4. extractionextract the aqueous layer with EtOAc
  5. dry with materialdry over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate under reduced pressure
  8. customPurify the residue by flash silica gel chromatography (gradient of 0 to 2% 2 M NH3/MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-9f8835368ba143b09314403810ccd57c
Source dataset
uspto-grants-2013_08
Patent number
US08507490B2

Reaction notes

Loading…