Cesium carbonate → tert-butyl N-[(3S)-1-[3-cyclopropyl-6-[6-(5-ethyl-3-pyridyl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-3-piperidyl]carbamate

HRID 57836Notes

Reaction equation

HRID 57836 reaction equation
Cl[C:2]1[C:3]([N:25]2[CH2:30][CH2:29][CH2:28][C@H:27]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:26]2)=[N:4][C:5]([N:8]2[C:16]3[CH:15]=[C:14]([C:17]4[CH:18]=[N:19][CH:20]=[C:21]([CH2:23][CH3:24])[CH:22]=4)[N:13]=[CH:12][C:11]=3[CH:10]=[N:9]2)=[CH:6][CH:7]=1.C(P(C12CC3CC(CC(C3)C1)C2)[C:44]12[CH2:53]C3CC(CC(C3)[CH2:45]1)C2)CCC.C(=O)([O-])[O-].[Cs+].[Cs+]>O.C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:53]1([C:2]2[C:3]([N:25]3[CH2:30][CH2:29][CH2:28][C@H:27]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:36])([CH3:35])[CH3:37])[CH2:26]3)=[N:4][C:5]([N:8]3[C:16]4[CH:15]=[C:14]([C:17]5[CH:18]=[N:19][CH:20]=[C:21]([CH2:23][CH3:24])[CH:22]=5)[N:13]=[CH:12][C:11]=4[CH:10]=[N:9]3)=[CH:6][CH:7]=2)[CH2:44][CH2:45]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneHCID 86707036tert-butyl N-[(3S)-1-[3-chloro-6-[6-(5-ethyl-3-pyridyl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-3-piperidyl]carbamate

Product 1

HCID 86707042tert-butyl N-[(3S)-1-[3-cyclopropyl-6-[6-(5-ethyl-3-pyridyl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-3-piperidyl]carbamateYield 248.6%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of tert-butyl N-[(3S)-1-[3-chloro-6-[6-(5-ethyl-3-pyridyl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-3-piperidyl]carbamate (0.0801 mmol; 42.8 mg), potassium cyclopropyl trifluoroborate (0.120 mmol; 18.3 mg), butyldi-1-adamantylphosphine (0.0240 mmol; 9.07 mg), cesium carbonate (0.240 mmol; 78.3 mg) and palladium (II) acetate (0.0160 mmol; 3.60 mg) in Water (0.5 mL) and Toluene (4.5 mL) was purged with Argon for 1 minute. The reaction mixture in a pressure tube was stirred at 105° C. for 3 days. The layers were separated. The organic later was concentrated. The residue was purified on silica eluted with 0 to 5% MeOH in DCM to afford tert-butyl N-[(3S)-1-[3-cyclopropyl-6-[6-(5-ethyl-3-pyridyl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-3-piperidyl]carbamate (32.2 mg, 74%).

Workup

  1. customwas purged with Argon for 1 minute
  2. customThe layers were separated
  3. concentrationThe organic later was concentrated
  4. customThe residue was purified on silica
  5. washeluted with 0 to 5% MeOH in DCM

Sources & evidence

ORD record
ord-4d77363e400c47958329ff2fdebc5423
Source dataset
uspto-grants-2016_09
Patent number
US09434725B2

Reaction notes

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