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

HRID 57902Notes

Reaction equation

HRID 57902 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]2[CH:8]=[N:9][N:10]([C:11]3[N:16]=[C:15]([N:17]4[CH2:22][CH2:21][CH2:20][C@H:19]([NH:23][C:24](=[O:26])[OH:25])[CH2:18]4)[C:14]([C:27]#[N:28])=[CH:13][CH:12]=3)[C:4]=2[CH:3]=1.C[Sn](C)(C)[C:31]1[CH:36]=[N:35][CH:34]=[C:33]([CH3:37])[N:32]=1>>[C:27]([C:14]1[C:15]([N:17]2[CH2:22][CH2:21][CH2:20][C@H:19]([NH:23][C:24](=[O:26])[O:25][C:5]([CH3:8])([CH3:6])[CH3:4])[CH2:18]2)=[N:16][C:11]([N:10]2[C:4]3[CH:3]=[C:2]([C:31]4[CH:36]=[N:35][CH:34]=[C:33]([CH3:37])[N:32]=4)[N:7]=[CH:6][C:5]=3[CH:8]=[N:9]2)=[CH:12][CH:13]=1)#[N:28]

Participants

3

Reactant 2

HCID 86707041Trimethyl-(6-methylpyrazin-2-yl)stannaneHCID 86707095[(3S)-1-[6-(6-chloropyrazolo[4,3-c]pyridin-1-yl)-3-cyano-2-pyridyl]-3-piperidyl]carbamic acid

Product 1

HCID 86707094tert-butyl N-[(3S)-1-[3-cyano-6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-3-piperidyl]carbamateYield 188.1%

Conditions

Temperature
150 °C

Procedure

A mixture of [(3S)-1-[6-(6-chloropyrazolo[4,3-c]pyridin-1-yl)-3-cyano-2-pyridyl]-3-piperidyl]carbamic acid (0.5166 mmol; 205.5 mg), trimethyl-(6-methylpyrazin-2-yl)stannane (0.7749 mmol; 199.1 mg), and palladium(0)tetrakis (triphenylphosphine); (0.05166 mmol; 59.8 mg) in N,N-Dimethylacetamide (12 mL) was purged with Argon. The reaction mixture was sealed in a pressure vial and heated at 150° C. for 2 hours. The mixture was cooled to room temperature, and then partitioned between EtOAc and water. The organic layer was concentrated and the residue was purified on silica eluted with 0 to 5% MeOH in DCM to afford tert-butyl N-[(3S)-1-[3-cyano-6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-3-piperidyl]carbamate as a yellow solid (248.6 mg, 94%).

Workup

  1. custom(0.05166 mmol; 59.8 mg) in N,N-Dimethylacetamide (12 mL) was purged with Argon
  2. customThe reaction mixture was sealed in a pressure vial
  3. temperatureThe mixture was cooled to room temperature
  4. custompartitioned between EtOAc and water
  5. concentrationThe organic layer was concentrated
  6. customthe residue was purified on silica
  7. washeluted with 0 to 5% MeOH in DCM

Sources & evidence

ORD record
ord-a311348f05c94eb38dfd7e00120e5e58
Source dataset
uspto-grants-2016_09
Patent number
US09434725B2

Reaction notes

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