Methanesulfonyl chloride → methanesulfonic acid 3-(3-cyano-1H-indol-4-yl)-3-phenyl-propyl ester

HRID 1716667Notes

Reaction equation

HRID 1716667 reaction equation
[OH:1][CH2:2][CH2:3][CH:4]([C:11]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:12]=1[C:13]([C:20]#[N:21])=[CH:14][NH:15]2)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH3:22][S:23](Cl)(=[O:25])=[O:24]>C1COCC1.C(Cl)Cl>[C:20]([C:13]1[C:12]2[C:16](=[CH:17][CH:18]=[CH:19][C:11]=2[CH:4]([C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:3][CH2:2][O:1][S:23]([CH3:22])(=[O:25])=[O:24])[NH:15][CH:14]=1)#[N:21]

Participants

4

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 673762644-(3-hydroxy-1-phenyl-propyl)-1H-indole-3-carbonitrile

Product 1

HCID 86612753methanesulfonic acid 3-(3-cyano-1H-indol-4-yl)-3-phenyl-propyl ester

Reagents, catalysts & solvents 1

HCID 21919333Tetrahydrofurane dichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° C. solution of 4-(3-hydroxy-1-phenyl-propyl)-1H-indole-3-carbonitrile LX (377 mg, 1.36 mmol) in THF/DCM (1/1, 22 ml) was added MsCl (105 μl, 1.36 mmol) dropwise. The mixture was stirred at 0° C. for 10 minutes, and TEA (226 μl, 1.62 mmol) was added dropwise. The resulting mixture was stirred at 0° C. for 2.5 hours, poured into ice/water, and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated affording methanesulfonic acid 3-(3-cyano-1H-indol-4-yl)-3-phenyl-propyl ester (not shown in above scheme) as a yellow oil. A solution of this crude mesylate in MeNH2 (33% in EtOH, 8.5 ml) was placed in a sealed tube and stirred at 100° C. for 45 minutes. The reaction mixture was concentrated, and the residue was partitioned between a saturated solution of NaHCO3 and EtOAc: The aqueous layer was extracted twice with EtOAc. The combined organic layers were dried over Na2SO4, filtered, concentrated, and purified via flash chromatography (DCM/MeOH/NH4OH) affording 4-(3-methylamino-1-phenyl-propyl)-1H-indole-3-carbonitrile LXI as a white foamy solid (346 mg). MS (M+H)=290.

Workup

  1. stirringThe resulting mixture was stirred at 0° C. for 2.5 hours
  2. extractionextracted with EtOAc
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-7ebd467153f941b2ad67a78aa3f7c30a
Source dataset
uspto-grants-2010_09
Patent number
US07803830B2

Reaction notes

Loading…