Nitrogen → 5-(3-(4-chloropyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amine

HRID 634101Notes

Reaction equation

HRID 634101 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[O:15][C:14]([NH:16][CH2:17][C:18]4[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=4)=[N:13][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.[Cl:36][C:37]1[CH:42]=[CH:41][N:40]=[C:39]([Sn](CCCC)(CCCC)CCCC)[N:38]=1.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>[Cl:36][C:37]1[CH:42]=[CH:41][N:40]=[C:39]([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([C:11]4[O:15][C:14]([NH:16][CH2:17][C:18]5[CH:19]=[CH:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=5)=[N:13][N:12]=4)[CH:9]=3)[N:4]([S:26]([C:29]3[CH:30]=[CH:31][C:32]([CH3:33])=[CH:34][CH:35]=3)(=[O:27])=[O:28])[CH:3]=2)[N:38]=1

Participants

7

Reactant 3

HCID 947Nitrogen2×HCID 149763044-Chloro-2-(tributylstannyl)pyrimidineHCID 683283255-(3-iodo-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amine

Product 1

HCID 867250935-(3-(4-chloropyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amineYield 53.3%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
80 °C

Procedure

A solution of 5-(3-iodo-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amine (3.0 g, 5.20 mmol) and 4-chloro-2-(tributylstannyl)pyrimidine (2.5 g, 6.00 mmol) in DMF was bubbled with N2 for 15 min. To the above mixture was added CuI (476 mg; 2.50 mmol) and Pd(PPh3)4 (577 mg, 0.52 mmol) and N2 gas was bubbled for another 15 min. The reaction was heated at 80° C. for 1 h. The reaction was quenched with H2O and the resulting precipitate was filtered, washed with H2O and dried. The crude material was purified with silica gel chromatography (eluting with 30% EtOAc in Hex) to give 5-(3-(4-chloropyrimidin-2-yl)-1-tosyl-1H-indol-5-yl)-N-(4-methoxybenzyl)-1,3,4-oxadiazol-2-amine (1.6 g, 53.3%). MS (ESI, pos. ion) m/z: 586.6 (M+1); 1H-NMR (400 MHz, DMSO-d6): δ 8.96 (s, 1H), 8.91 (d, J=4 Hz, 1H), 8.62 (s, 1H), 8.35 (m, 1H), 8.17 (d, J=8 Hz, 1H), 8.10 (d, J=8 Hz, 2H), 7.91 (d, J=8 Hz, 1H), 7.65-7.62 (m, 2H), 7.45-7.43 (m, 6H), 7.33 (d, J=8 Hz, 2H), 6.90 (d, J=8 Hz, 2H), 4.38 (d, J=5.6 Hz, 2H), 3.72 (s, 3H), 2.33 (s, 3H).

Workup

  1. customwas bubbled for another 15 min
  2. customThe reaction was quenched with H2O
  3. filtrationthe resulting precipitate was filtered
  4. washwashed with H2O
  5. customdried
  6. customThe crude material was purified with silica gel chromatography (eluting with 30% EtOAc in Hex)

Sources & evidence

ORD record
ord-2edc13146d2f4260bcfd0538f1dea4e2
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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