Nitrogen → tert-butyl (3-(3-(6-(isopropylamino)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,2,4-thiadiazol-5-yl)carbamate

HRID 634266Notes

Reaction equation

HRID 634266 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][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[S:13][N:12]=3)[CH:9]=2)[N:4]([S:24]([C:27]2[CH:33]=[CH:32][C:30]([CH3:31])=[CH:29][CH:28]=2)(=[O:26])=[O:25])[CH:3]=1.[CH:34]([NH:37][C:38]1[CH:43]=[N:42][CH:41]=[C:40]([Sn](CCCC)(CCCC)CCCC)[N:39]=1)([CH3:36])[CH3:35].N#N>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:34]([NH:37][C:38]1[N:39]=[C:40]([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([C:11]4[N:15]=[C:14]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:20])([CH3:21])[CH3:22])[S:13][N:12]=4)[CH:9]=3)[N:4]([S:24]([C:27]3[CH:28]=[CH:29][C:30]([CH3:31])=[CH:32][CH:33]=3)(=[O:26])=[O:25])[CH:3]=2)[CH:41]=[N:42][CH:43]=1)([CH3:36])[CH3:35]

Participants

7

Reactant 3

HCID 947NitrogenHCID 68328197N-isopropyl-6-(tributylstannyl)pyrazin-2-amineHCID 86725113tert-butyl 3-(3-iodo-1-tosyl-1H-indol-5-yl)-1,2,4-thiadiazol-5-ylcarbamate

Product 1

HCID 86725115tert-butyl (3-(3-(6-(isopropylamino)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,2,4-thiadiazol-5-yl)carbamateYield 81%

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

A mixture of tert-butyl (3-(3-iodo-1-tosyl-1H-indol-5-yl)-1,2,4-thiadiazol-5-yl)carbamate (0.6 g, 1.0 mmol) and N-isopropyl-6-(tributylstannyl)pyrazin-2-amine (0.429 g, 1.0 mmol) in DMF (10 mL) was bubbled N2 gas for 15 min. To the mixture was added CuI (95 mg, 0.5 mmol.) and Pd(PPh3)4 (12 mg, 0.1 mmol) and N2 gas was bubbled for another 15 min. The reaction was heated at 90° C. for 1 h. The mixture was quenched with H2O (10 mL) and extracted with CHCl3 (2×25 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude was purified by neutral alumina column chromatography (eluent: 20% EtOAc in petroleum ether) to give tert-butyl (3-(3-(6-(isopropylamino)pyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-1,2,4-thiadiazol-5-yl)carbamate (0.49 g, 81%). MS (ESI, pos. ion) m/z: 606.1 (M+1).

Workup

  1. customwas bubbled N2 gas for 15 min
  2. customwas bubbled for another 15 min
  3. customThe mixture was quenched with H2O (10 mL)
  4. extractionextracted with CHCl3 (2×25 mL)
  5. dry with materialThe organic layer was dried over anhydrous Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe crude was purified by neutral alumina column chromatography (eluent: 20% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-b1b8f7a2fd7d4f85a4da0cee7e948883
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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