2-Isopropoxy-6-(trimethylstannyl)pyrazine → 3-(3-(6-isopropoxypyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,2,4-oxadiazol-5-amine

HRID 634286Notes

Reaction equation

HRID 634286 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[N:15]=[C:14]([NH:16][CH:17]([CH3:19])[CH3:18])[O:13][N:12]=3)[CH:9]=2)[N:4]([S:20]([C:23]2[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=2)(=[O:22])=[O:21])[CH:3]=1.[CH:30]([O:33][C:34]1[CH:39]=[N:38][CH:37]=[C:36]([Sn](C)(C)C)[N:35]=1)([CH3:32])[CH3:31]>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:30]([O:33][C:34]1[N:35]=[C:36]([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([C:11]4[N:15]=[C:14]([NH:16][CH:17]([CH3:18])[CH3:19])[O:13][N:12]=4)[CH:9]=3)[N:4]([S:20]([C:23]3[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=3)(=[O:21])=[O:22])[CH:3]=2)[CH:37]=[N:38][CH:39]=1)([CH3:32])[CH3:31]

Participants

6

Reactant 2

HCID 683280402-Isopropoxy-6-(trimethylstannyl)pyrazineHCID 683287503-(3-iodo-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,2,4-oxadiazol-5-amine

Product 1

HCID 683287123-(3-(6-isopropoxypyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,2,4-oxadiazol-5-amineYield 43.7%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
90 °C

Procedure

Argon gas was bubbled through a solution of 3-(3-iodo-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,2,4-oxadiazol-5-amine (450 mg, 0.86 mmol) and 2-isopropoxy-6-(trimethylstannyl)pyrazine (311 mg, 1.03 mmol) in dry DMF (4.5 ml) for 15 min. To the mixture was added CuI (163 mg, 0.86 mmol) and Pd(PPh3)4 (99 mg, 0.086 mmol) and argon gas was further bubbled for additional 15 min. The reaction was heated at 90° C. for 1 h then cooled to RT. The reaction was quenched with ice cold water. The resulting suspension was filtered and washed with water. The solid was purified with basic alumina column chromatography (eluent: 20% EtOAc in petroleum ether) to give 3-(3-(6-isopropoxypyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,2,4-oxadiazol-5-amine (200 mg, 43.5%). MS (ESI, pos. ion) m/z: 533.3 (M+1).

Workup

  1. customwas further bubbled for additional 15 min
  2. temperaturethen cooled to RT
  3. customThe reaction was quenched with ice cold water
  4. filtrationThe resulting suspension was filtered
  5. washwashed with water
  6. customThe solid was purified with basic alumina column chromatography (eluent: 20% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-deda81e4034e4a0e942851c42cd673c4
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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