Triethylamine → HCID 15745345, compound

HRID 359453Notes

Reaction equation

HRID 359453 reaction equation
[CH:1]([S:3]([CH2:6][CH3:7])(=[O:5])=[O:4])=[CH2:2].Br[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[CH:18]1[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([S:3](/[CH:6]=[CH:7]/[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[CH:18]1[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]1)(=[O:5])=[O:4])[CH3:2]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 74680(Ethylsulfonyl)etheneHCID 80271Tri-o-tolylphosphineHCID 157453445-bromo-3-(1-methylpiperidin-4-yl)-1H-indole

Product 1

HCID 15745345HCID 15745345, compoundYield 66.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of ethyl vinyl sulphone (600 mg), 5-bromo-3-(1-methyl-4-piperidinyl)-1H-indole (1.00 g), palladium acetate (50 mg), tri-o-tolylphosphine (244 mg) and triethylamine (700 mg) in dry dimethylformamide (10 ml) was stirred and heated at 100°-110° for 4 h. The dimethylformamide and triethylamine were removed in vacuo. The residual gum was chromatographed on silica (140 g; Merck 9385), using a mixture of dichloromethane, ethanol and ammonia (80:8:1) as the eluant, to give a gum (750 mg). The material was rechromatographed on silica (Merck 9385; 100 g), using a mixture of dichloromethane, ethanol and ammonia (90:8:1) as the eluant. Fractions containing mainly the product were combined and evaporated to give a gum. A few fractions contained small amounts of the pure product. These were kept separate, combined and evaporated. The residual gum was crystallised from a small amount of a mixture of ethyl acetate and cyclohexane. Some of the crystals were then used to seed the crystallisation of the main batch of the product, also from a mixture of ethyl acetate and cyclohexane. The two batches of solid product were combined and dried in vacuo to give the title compound (310 mg) as a powder, with m.p. 98°-102°.

Workup

  1. temperatureheated at 100°-110° for 4 h
  2. customThe dimethylformamide and triethylamine were removed in vacuo
  3. customThe residual gum was chromatographed on silica (140 g; Merck 9385)
  4. additiona mixture of dichloromethane, ethanol and ammonia (80:8:1) as the eluant

Sources & evidence

ORD record
ord-970aa2ae9c724eea9b6dc80247b59ce1
Source dataset
uspto-grants-1991_03
Patent number
US05001135

Reaction notes

Loading…