Water → HCID 59743501, compound

HRID 1947002Notes

Reaction equation

HRID 1947002 reaction equation
[CH2:1]([S:8][C:9]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:10]=1[CH:11]=[CH:12][NH:13]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:21]1[N:26]=[C:25]([Cl:27])[CH:24]=[CH:23][N:22]=1.O>CN(C=O)C>[CH2:1]([S:8][C:9]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:10]=1[CH:11]=[CH:12][N:13]2[C:21]1[N:26]=[C:25]([Cl:27])[CH:24]=[CH:23][N:22]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 775312,4-DichloropyrimidineHCID 24971563HCID 24971563, compound

Product 1

HCID 59743501HCID 59743501, compoundYield 14%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

4-Benzylsulfanyl-1H-indole (5.00 g, 21 mmol) (Can. J. Chem. 1962, 40, 511) was slowly added to a suspension of NaH (60% dispersion in mineral oil, 1.37 g, 34 mmol) in DMF (40 mL) at 0° C. The reaction mixture was stirred for 15 min until the gas evolution ceased, then 2,4-di-chloropyrimidine (3.03 g, 20 mmol) was added portionwise, followed by an additional aliquot of DMF (10 mL). The resulting mixture was slowly warmed to RT, then poured onto a slurry of ice and water and extracted with EtOAc. The organic layer was washed twice with a mixture of water and brine, dried over Na2SO4, filtered and evaporated under reduced pressure. The crude residue was purified by flash chromatography (EtOAc/hexanes, gradient from 10:90 to 50:50) to give 4-benzylsulfanyl-1-(4-chloropyrimidin-2-yl)-1H-indole (979 mg, 14% yield) as a pale-yellow waxy solid and a mixture of 4-benzylsulfanyl-1-(2-chloropyrimidin-4-yl)-1H-indole and the bisubstituted product (691 mg) after precipitation from DCM/EtOAc. This mixture was repurified by flash chromatography (EtOAc/hexanes, 20:80) to give 4-benzylsulfanyl-1-(2-chloropyrimidin-4-yl)-1H-indole (270 mg, 4% yield) as an off-white solid. MS=352 [M+H]+; MP=159.0-161.2° C.

Workup

  1. extractionextracted with EtOAc
  2. washThe organic layer was washed twice with a mixture of water and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customThe crude residue was purified by flash chromatography (EtOAc/hexanes, gradient from 10:90 to 50:50)

Sources & evidence

ORD record
ord-6a3a8e63f3d14ceba46853e2ec6b1d56
Source dataset
uspto-grants-2013_03
Patent number
US08399462B2

Reaction notes

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