2-Isopropoxy-6-(tributylstannyl)pyridine → 5-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,2,4-thiadiazol-3-amine

HRID 634253Notes

Reaction equation

HRID 634253 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[S:15][N:14]=[C:13]([NH:16][CH2:17][C:18]4[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=4)[N:12]=3)[CH:9]=2)[N:4]([S:26]([C:29]2[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=2)(=[O:28])=[O:27])[CH:3]=1.[CH:36]([O:39][C:40]1[CH:45]=[CH:44][CH:43]=[C:42]([Sn](CCCC)(CCCC)CCCC)[N:41]=1)([CH3:38])[CH3:37]>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:36]([O:39][C:40]1[N:41]=[C:42]([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([C:11]4[S:15][N:14]=[C:13]([NH:16][CH2:17][C:18]5[CH:19]=[CH:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=5)[N:12]=4)[CH:9]=3)[N:4]([S:26]([C:29]3[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=3)(=[O:28])=[O:27])[CH:3]=2)[CH:43]=[CH:44][CH:45]=1)([CH3:38])[CH3:37]

Participants

6

Reactant 2

HCID 683286192-Isopropoxy-6-(tributylstannyl)pyridineHCID 683287145-(3-iodo-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,2,4-thiadiazol-3-amine

Product 1

HCID 683283525-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,2,4-thiadiazol-3-amineYield 43.4%

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 solution of 5-(3-iodo-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,2,4-thiadiazol-3-amine (0.8 g, 1.29 mmol) and 2-isopropoxy-6-(tributylstannyl)pyridine (0.83 g, 1.95 mmol) in DMF (8 mL) was bubbled with Argon for 15 min. To the above mixture was added CuI (0.124 g, 0.65 mmol) and Pd(PPh3)4 (0.15 g, 0.13 mmol) and argon gas was purged for another 15 min. The reaction was heated at 90° C. for 1 h. The mixture was treated with ice cold water (20 mL) to obtain off white precipitate. The precipitate was filtered, washed with H2O (20 mL) and dried. The solid was purified by basic alumina chromatography (eluent: 20% EtOAc in petroleum ether) to give 5-(3-(6-isopropoxypyridin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,2,4-thiadiazol-3-amine (0.35 g, 43%) as a white solid. MS (ESI, pos. ion) m/z: 625.2 (M+1); 1H-NMR (400 MHz, CDCl3): δ 9.02 (d, J=1.2 Hz, 1H), 8.10-8.08 (m, 2H), 7.96 (dd, J=8.8, 2.0 Hz, 1H), 7.83 (d, J=8.4 Hz, 2H), 7.64 (t, J=8.0 Hz, 1H), 7.34-7.24 (m, 2H) 4.62 (d, J=5.6 Hz, 2H), 3.80 (s, 3H), 2.35 (s, 3H), 1.46 (d, J=5.6 Hz, 6H).

Workup

  1. customwas purged for another 15 min
  2. additionThe mixture was treated with ice cold water (20 mL)
  3. customto obtain off white precipitate
  4. filtrationThe precipitate was filtered
  5. washwashed with H2O (20 mL)
  6. customdried
  7. customThe solid was purified by basic alumina chromatography (eluent: 20% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-64b58d684776456f85556c940f3c4a00
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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