4-(N-Boc-amino)piperidine → tert-butyl 1-(6-(5-(2-chloro-6-fluorophenyl)-1-tosyl-1H-indol-3-yl)pyrazin-2-yl)piperidin-4-ylcarbamate

HRID 1529321Notes

Reaction equation

HRID 1529321 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([S:18]([C:21]1[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=1)(=[O:20])=[O:19])[CH:13]=[C:12]2[C:28]1[CH:33]=[N:32][CH:31]=[C:30](Cl)[N:29]=1.[NH:35]1[CH2:40][CH2:39][CH:38]([NH:41][C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45])[CH2:37][CH2:36]1>CS(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([S:18]([C:21]1[CH:22]=[CH:23][C:24]([CH3:25])=[CH:26][CH:27]=1)(=[O:19])=[O:20])[CH:13]=[C:12]2[C:28]1[N:29]=[C:30]([N:35]2[CH2:36][CH2:37][CH:38]([NH:41][C:42](=[O:48])[O:43][C:44]([CH3:46])([CH3:45])[CH3:47])[CH2:39][CH2:40]2)[CH:31]=[N:32][CH:33]=1

Participants

4

Reactant 2

HCID 7238334-(N-Boc-amino)piperidineHCID 867097705-(2-chloro-6-fluorophenyl)-3-(6-chloropyrazin-2-yl)-1-tosyl-1H-indole

Product 1

HCID 67960004tert-butyl 1-(6-(5-(2-chloro-6-fluorophenyl)-1-tosyl-1H-indol-3-yl)pyrazin-2-yl)piperidin-4-ylcarbamateYield 70.5%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A slurry of 5-(2-chloro-6-fluorophenyl)-3-(6-chloropyrazin-2-yl)-1-tosyl-1H-indole (Ref, 0.200 g, 0.390 mmol) and tert-butyl piperidin-4-ylcarbamate (Combi-blocks Inc., 0.313 g, 1.561 mmol) in 2 mL DMSO in a sealed tube was heated to 130° C. The solids dissolved and the reaction became a yellow solution. After 1 h, reaction was complete by LCMS. The reaction was cooled and partitioned between water and EtOAc. The organic layer was washed with water once, satd NaHCO3 once, satd NaCl once, and the organics were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was suspended in MeOH and filtered, rinsing 1×1 mL MeOH. The solid was collected and dried in vacuo to give tert-butyl 1-(6-(5-(2-chloro-6-fluorophenyl)-1-tosyl-1H-indol-3-yl)pyrazin-2-yl)piperidin-4-ylcarbamate (0.186 g, 0.275 mmol, 70.5% yield) as a light yellow solid. MS (ESI, pos. ion) m/z: 676 (M+1).

Workup

  1. dissolutionThe solids dissolved
  2. customreaction
  3. temperatureThe reaction was cooled
  4. custompartitioned between water and EtOAc
  5. washThe organic layer was washed with water once
  6. dry with materialthe organics were dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. filtrationfiltered
  10. washrinsing 1×1 mL MeOH
  11. customThe solid was collected
  12. customdried in vacuo

Sources & evidence

ORD record
ord-6e10a215222045239d831ab59ca3334f
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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