Triethylamine → 3-(4-Ethylthio-5-(4-methyl-1,2-dioxocyclobut-3-en-3-yl)amino-3-indolyl)1-propanol

HRID 441101Notes

Reaction equation

HRID 441101 reaction equation
[NH2:1][C:2]1[C:3]([S:15][CH2:16][CH3:17])=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][CH2:13][OH:14].Cl[C:19]1[C:20](=[O:25])[C:21](=[O:24])[C:22]=1[CH3:23].CCN(CC)CC.[K+].[Br-]>CN(C=O)C.O>[CH2:16]([S:15][C:3]1[C:2]([NH:1][C:19]2[C:20](=[O:25])[C:21](=[O:24])[C:22]=2[CH3:23])=[CH:10][CH:9]=[C:8]2[C:4]=1[C:5]([CH2:11][CH2:12][CH2:13][OH:14])=[CH:6][NH:7]2)[CH3:17]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 253877Potassium BromideHCID 126143603-Chloro-4-methylcyclobut-3-ene-1,2-dioneHCID 224056733-(5-Amino-4-ethylthio-3-indolyl)-1-propanol

Product 1

HCID 224057163-(4-Ethylthio-5-(4-methyl-1,2-dioxocyclobut-3-en-3-yl)amino-3-indolyl)1-propanol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
23 °C

Procedure

A mixture of 3-(5-amino-4-ethylthio-3-indolyl)-1-propanol (0.93 g, 3.7 mmol), 3-chloro-4-methyl-1,2-dioxocyclobut-3-ene (0.58 g, 4.4 mmol) and Et3N (0.62 ml, 4.4 mmol) in DMF (50 ml) was stirred at 23° C. for 50 h before adding water (200 ml). The aqueous solution was extracted with EtOAc (3×75 ml). The organic extracts were washed with water (50 ml), dried (MgSO4) and concentrated in vacuo. The crude material was purified on silica gel dry column using first a mixture of CH2Cl2 :EtOAc (1:4) and then EtOAc:Et3N (49:1). Appropriate fractions were concentrated in vacuo leaving yellow crystals, 0.815 g, m.p. 119° C., 64%. 1H NMR (DMSO-d6) δ (ppm): 11.17, 11.11, 10.80 and 10.51 (4 br s, 2H indolic NH, and 5-NH), 7.4 (br s, 1H), 7.26 (s, 1H), 7.07 (d, J=8.2 Hz, 1H), 4.40 (t, J=5.2 Hz, 1H, OH), 3.46 (t, J=3.5 Hz, 2H after D2O exchange), 2.95-3.10 (m, 2H, CH2CH2CH2O), 2.66 (br s, 2H, CH3CH 2 S), 2.26 (br s, 1H, CH3 on dioxocyclobutene), 1.7-1.9 (m, 2H, CH2CH2CH2O), 1.59 (br s, 2H, CH3 on dioxocyclobutene), 0.9-1.1 (m, 3H, CH3CH2S). IR (KBr) n:3420, 3300-3000, 1775, 1728, 1620, 1580 and 1400 cm-1. Anal. calcd. for: C18H20N2O3S: C 62.77; H 5.85; N 8.13; S 9.31. Found: C 62.75; H 5.85; N 8.20; S 9.25.

Workup

  1. extractionThe aqueous solution was extracted with EtOAc (3×75 ml)
  2. washThe organic extracts were washed with water (50 ml)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified on silica gel
  6. customdry column
  7. additiona mixture of CH2Cl2 :EtOAc (1:4)
  8. concentrationAppropriate fractions were concentrated in vacuo
  9. customleaving yellow crystals, 0.815 g, m.p. 119° C., 64%

Sources & evidence

ORD record
ord-a0ab3789bf444a6594190f96e100947e
Source dataset
uspto-grants-1996_05
Patent number
US05521188

Reaction notes

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