Triethylamine → 4-Methyl-5-(1,2-dioxo-4-methyl-3-cyclobuten-3-yl)amino-3-(3-methanesulfonyloxypropyl)indole

HRID 441098Notes

Reaction equation

HRID 441098 reaction equation
[CH3:1][C:2]1[C:10]([NH:11][C:12]2[C:13](=[O:18])[C:14](=[O:17])[C:15]=2[CH3:16])=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([CH2:19][CH2:20][CH2:21][OH:22])=[CH:5][NH:6]2.C(N(CC)CC)C.[CH3:30][S:31](Cl)(=[O:33])=[O:32]>C(#N)C.C1COCC1.C(OCC)(=O)C>[CH3:1][C:2]1[C:10]([NH:11][C:12]2[C:13](=[O:18])[C:14](=[O:17])[C:15]=2[CH3:16])=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([CH2:19][CH2:20][CH2:21][O:22][S:31]([CH3:30])(=[O:33])=[O:32])=[CH:5][NH:6]2

Participants

6

Reactant 3

HCID 8471Triethylamine2×HCID 31297Methanesulfonyl chloride2×HCID 224056854-Methyl-5-(1,2-dioxo-4-methyl-3-cyclobuten-3-yl)amino-3-(3-hydroxypropyl)indole

Product 1

HCID 224057024-Methyl-5-(1,2-dioxo-4-methyl-3-cyclobuten-3-yl)amino-3-(3-methanesulfonyloxypropyl)indoleYield 91%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 22177404Acetonitrile tetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To an ice-cold suspension of 4-methyl-5-(1,2-dioxo-4-methyl-3-cyclobuten-3-yl)amino-3-(3-hydroxypropyl)indole (0.235 g, 0.79 mmol) in 5 mL of acetonitrile-THF (4:1) was added triethylamine (0.132 mL, 0.95 mmol), followed by methanesulfonyl chloride (0.074 mL, 0.95 mmol). The mixture was stirred at 0° C. for 2 h and then the cooling bath was removed and stirring continued at room temperature for 17 h. Another 0.026 mL (0.19 mmol) of triethylamine and 0.015 mL (0.19 mmol) of methanesulfonyl chloride were then added and stirring was continued for 30 min. The resulting mixture was diluted with ethyl acetate, washed (H2O×2; brine), dried (Na2SO4) and evaporated to give a gum. This material was chromatographed (SiO2 /ethyl acetate-dichloromethane, 1:1) to give to give the title compound (0.270 g, 91%) as an off-white foam. An analytical sample was obtained by crystallization from ether to give an off-white solid, mp 130°-131° C. (dec): IR (KBr) 3240 (br), 1792, 1727, 1590, 1330, 920 cm-1 ; 1H NMR (DMSO-d6, 200 MHz) δ 11.01 (br s, 0.75H), 10.95 (br s, 0.25H), 10.58 (s, 0.75H), 10.31 (s, 0.25H), 7.23-7.13 (m, 2H), 6.94 (d, J=8.5 Hz, 0.75H), 6.88 (d, J=8.6 Hz, 0.25H), 4.29 (t, J=6.3 Hz, 2H), 3.19 (s, 3H), 2.96 (m, 2H), 2.50 (s, 3H), 2.24 (s, 0.75H), 2.02 (m, 2H), 1.56 (s, 2.25H). Anal. Calcd for C18H20N2O5S: C, 57.43; H, 5.36; N, 7.44. Found: C, 57.16; H, 5.00; N, 7.34.

Workup

  1. customthe cooling bath was removed
  2. stirringstirring
  3. waitcontinued at room temperature for 17 h
  4. stirringstirring
  5. waitwas continued for 30 min
  6. washwashed (H2O×2; brine)
  7. dry with materialdried (Na2SO4)
  8. customevaporated
  9. customto give a gum
  10. customThis material was chromatographed (SiO2 /ethyl acetate-dichloromethane, 1:1)
  11. customto give

Sources & evidence

ORD record
ord-ecd77dfe1c0c4afa85a8a25c19c6238c
Source dataset
uspto-grants-1996_05
Patent number
US05521188

Reaction notes

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