Nitrogen → 5-(3-(6-isopropoxypyridin-2-yl)-1H-indol-5-yl)-1,2,4-oxadiazol-3-amine

HRID 634272Notes

Reaction equation

HRID 634272 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[O:15][N:14]=[C:13]([NH2:16])[N:12]=3)[CH:9]=2)[NH:4][CH:3]=1.[CH:17]([O:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([Sn](CCCC)(CCCC)CCCC)[N:22]=1)([CH3:19])[CH3:18].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:17]([O:20][C:21]1[N:22]=[C:23]([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([C:11]4[O:15][N:14]=[C:13]([NH2:16])[N:12]=4)[CH:9]=3)[NH:4][CH:3]=2)[CH:24]=[CH:25][CH:26]=1)([CH3:19])[CH3:18]

Participants

7

Reactant 3

HCID 947Nitrogen2×HCID 68328272HCID 68328272, compoundHCID 683286192-Isopropoxy-6-(tributylstannyl)pyridine

Product 1

HCID 683567385-(3-(6-isopropoxypyridin-2-yl)-1H-indol-5-yl)-1,2,4-oxadiazol-3-amineYield 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

To a solution of 5-(3-iodo-1H-indol-5-yl)-1,2,4-oxadiazol-3-amine (0.3 g, 0.92 mmol) and 2-isopropoxy-6-(tributylstannyl)pyridine (0.471 g, 1.1 mmol) in DMF (10 mL) was bubbled with N2 gas for 15 min. To the mixture was added CuI (0.140 g, 0.73 mmol) and Pd(PPh3)4 (0.100 g, 0.092 mmol) and N2 gas was bubbled for another 15 min. The reaction was heated at 90° C. for 1 h. The reaction mixture was cooled to RT, and quenched with water (100 mL) and extracted in EtOAc (2×100 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated. The residue was purified with preparative HPLC (eluent: 30-70% MeCN in water with 0.01% TFA) to afford 5-(3-(6-isopropoxypyridin-2-yl)-1H-indol-5-yl)-1,2,4-oxadiazol-3-amine (0.01 g, 7%) as a white solid. MS (ESI, pos. ion) m/z: 336.2 (M+1); 1H-NMR (400 MHz, CD3OD): δ 9.36 (s, 1H), 7.99 (s, 1H), 7.89 (d, J=8.4 Hz, 1H), 7.64 (m, 2H), 7.37 (d, J=7.6 Hz, 1H), 6.52 (d, J=8.4 Hz, 1H), 5.65 (m, 1H), 1.51 (d, J=6.0 Hz, 6H).

Workup

  1. customwas bubbled for another 15 min
  2. temperatureThe reaction mixture was cooled to RT
  3. customquenched with water (100 mL)
  4. extractionextracted in EtOAc (2×100 mL)
  5. dry with materialThe organic layer was dried over anhydrous Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified with preparative HPLC (eluent: 30-70% MeCN in water with 0.01% TFA)

Sources & evidence

ORD record
ord-778534f2e819478da1c3910fefc89d8c
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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