Triethylamine → 5-[3,3-dimethyl-1-(methylsulfonyl)-2,3-dihydro-1H-indol-5-yl]-1-methyl-1H-pyrrole-2-carbonitrile

HRID 2353452Notes

Reaction equation

HRID 2353452 reaction equation
Cl.[CH3:2][C:3]1([CH3:20])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]3[N:16]([CH3:17])[C:15]([C:18]#[N:19])=[CH:14][CH:13]=3)[CH:10]=2)[NH:5][CH2:4]1.C(N(CC)CC)C.[CH3:28][S:29](Cl)(=[O:31])=[O:30]>C(Cl)Cl.C(OCC)(=O)C>[CH3:2][C:3]1([CH3:20])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]3[N:16]([CH3:17])[C:15]([C:18]#[N:19])=[CH:14][CH:13]=3)[CH:10]=2)[N:5]([S:29]([CH3:28])(=[O:31])=[O:30])[CH2:4]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 68426111HCID 68426111, compound

Product 1

HCID 250035415-[3,3-dimethyl-1-(methylsulfonyl)-2,3-dihydro-1H-indol-5-yl]-1-methyl-1H-pyrrole-2-carbonitrileYield 63.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-(3,3-dimethyl-2,3-dihydro-1H-indol-5-yl)-1-methyl-1H-pyrrole-2-carbonitrile hydrochloride (288 mg, 1.0 mmol) was dissolved in methylene chloride (5 mL) and triethylamine (0.43 mL, 3.0 mmol) was added. The mixture was treated with methanesulfonyl chloride (0.078 mL, 1.1 mmol) and stirred for 3 hours. The mixture was diluted with ethyl acetate, washed with water, 2N HCl, water, brine, dried over anhydrous magnesium sulfate, and concentrated. The crude product was purified via Isco chromatography (the Redisep® column, silica, gradient 10-60% ethyl acetate in hexane) to afford 5-[3,3-dimethyl-1-(methylsulfonyl)-2,3-dihydro-1H-indol-5-yl]-1-methyl-1H-pyrrole-2-carbonitrile (0.21 g). MS (EI) m/z 329.8; HPLC purity 100.0% at 210-370 nm, 9.5 min.; the Xterra® RP18 column, 3.5μ, 150×4.6 mm column, 1.2 mL/min, 85/15-5/95 (Ammonium formate buffer pH=3.5 acetonitrile+MeOH) for 10 minutes, hold 4 minutes.

Workup

  1. washwashed with water, 2N HCl, water, brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. concentrationconcentrated
  4. customThe crude product was purified via Isco chromatography (the Redisep® column, silica, gradient 10-60% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-6a20784f0dd24de296d237e2c5090ff5
Source dataset
uspto-grants-2010_07
Patent number
US07750038B2

Reaction notes

Loading…