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

HRID 57892Notes

Reaction equation

HRID 57892 reaction equation
Cl[C:2]1[C:3]([N:24]2[CH2:29][CH2:28][CH2:27][C@H:26]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:25]2)=[N:4][C:5]([N:8]2[C:16]3[CH:15]=[C:14]([C:17]4[CH:22]=[N:21][CH:20]=[C:19]([CH3:23])[N:18]=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:43]12[CH2:52]C3CC(CC(C3)[CH2:44]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:52]1([C:2]2[C:3]([N:24]3[CH2:29][CH2:28][CH2:27][C@H:26]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:34])[CH3:35])[CH2:25]3)=[N:4][C:5]([N:8]3[C:16]4[CH:15]=[C:14]([C:17]5[CH:22]=[N:21][CH:20]=[C:19]([CH3:23])[N:18]=5)[N:13]=[CH:12][C:11]=4[CH:10]=[N:9]3)=[CH:6][CH:7]=2)[CH2:43][CH2:44]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneHCID 86707081tert-butyl N-[(3S)-1-[3-chloro-6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-3-piperidyl]carbamate

Product 1

HCID 86707084tert-butyl N-[(3S)-1-[3-cyclopropyl-6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-3-piperidyl]carbamateYield 367%

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-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-3-piperidyl]carbamate (0.2225 mmol; 115.9 mg), potassium cyclopropyl trifluoroborate (0.3337 mmol; 50.90 mg), butyldi-1-adamantylphosphine (0.06674 mmol; 25.19 mg), cesium carbonate (0.6674 mmol; 217.4 mg) and palladium(II) acetate (0.04449 mmol; 9.994 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-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-3-piperidyl]carbamate (129 mg, ˜100%).

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-731bf0280233449eba7979106a5e691d
Source dataset
uspto-grants-2016_09
Patent number
US09434725B2

Reaction notes

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