Water → (R)-tert-butyl 3-(6-(5-(6-isopropoxy-pyrazin-2-yl)-1-tosyl-1H-indol-3-yl)pyrazin-2-ylamino)piperidine-1-carboxylate

HRID 1529312Notes

Reaction equation

HRID 1529312 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[CH:16]=[N:15][CH:14]=[C:13]([O:17][CH:18]([CH3:20])[CH3:19])[N:12]=3)[CH:9]=2)[N:4]([S:21]([C:24]2[CH:30]=[CH:29][C:27]([CH3:28])=[CH:26][CH:25]=2)(=[O:23])=[O:22])[CH:3]=1.C([Sn](CCCC)(CCCC)[C:36]1[N:41]=[C:40]([NH:42][C@@H:43]2[CH2:48][CH2:47][CH2:46][N:45]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[CH2:44]2)[CH:39]=[N:38][CH:37]=1)CCC.O>CN(C=O)C.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:18]([O:17][C:13]1[N:12]=[C:11]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[N:4]([S:21]([C:24]2[CH:25]=[CH:26][C:27]([CH3:28])=[CH:29][CH:30]=2)(=[O:22])=[O:23])[CH:3]=[C:2]3[C:36]2[N:41]=[C:40]([NH:42][C@@H:43]3[CH2:48][CH2:47][CH2:46][N:45]([C:49]([O:51][C:52]([CH3:53])([CH3:54])[CH3:55])=[O:50])[CH2:44]3)[CH:39]=[N:38][CH:37]=2)[CH:16]=[N:15][CH:14]=1)([CH3:20])[CH3:19]

Participants

7

Reactant 3

HCID 962WaterHCID 679596923-iodo-5-(6-isopropoxypyrazin-2-yl)-1-tosyl-1H-indoleHCID 86709769(R)-tert-butyl 3-(6-(tributylstannyl)pyrazin-2-ylamino)piperidine-1-carboxylate

Product 1

HCID 67959931(R)-tert-butyl 3-(6-(5-(6-isopropoxy-pyrazin-2-yl)-1-tosyl-1H-indol-3-yl)pyrazin-2-ylamino)piperidine-1-carboxylateYield 57%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

3-Iodo-5-(6-isopropoxypyrazin-2-yl)-1-tosyl-1H-indole (0.4 g, 0.753 mmol) and (R)-tert-butyl 3-(6-(tributylstannyl)pyrazin-2-ylamino)piperidine-1-carboxylate (0.51 g, 0.903 mmol) in DMF (10 mL) was purged with argon for 15 min and added CuI (225 mg, 1.18 mmol) and Pd(PPh3)4 (105 mg, 0.09 mmol). The reaction mixture was heated at 100° C. for 2 h and cooled to RT. To the reaction mixture was added water and precipitate was formed. The precipitate was collected by filtration, washed with water and dried overnight. The crude product was purified by chromatography (eluting with 50% EtOAc/hexane) to obtain (R)-tert-butyl 3-(6-(5-(6-isopropoxy-pyrazin-2-yl)-1-tosyl-1H-indol-3-yl)pyrazin-2-ylamino)piperidine-1-carboxylate (0.2 g, 57%). MS (ESI, pos. ion) m/z: 684 (M+1).

Workup

  1. temperaturecooled to RT
  2. customprecipitate was formed
  3. filtrationThe precipitate was collected by filtration
  4. washwashed with water
  5. customdried overnight
  6. customThe crude product was purified by chromatography (eluting with 50% EtOAc/hexane)

Sources & evidence

ORD record
ord-f43fb7b47dfc422eb492343264dd7b0f
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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