Triethylamine → HCID 57474450, compound

HRID 2043492Notes

Reaction equation

HRID 2043492 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][C:13]([OH:15])=O.Cl.[CH3:17][N:18](C)[CH2:19]CCN=C=NCC.ON1C2C=CC=CC=2N=N1.Cl.CNC.C(N(CC)CC)C>CN(C=O)C.CCCCCC.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][C:13]([N:18]([CH3:19])[CH3:17])=[O:15]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 10473Dimethylamine, hydrochlorideHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 184500383-(5-Bromo-1H-indol-3-yl)propanoic acid

Product 1

HCID 57474450HCID 57474450, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a 250 mL argon purged round bottom flask fitted with a magnetic stirbar containing a yellow solution of 5-bromo-indol-3-propionic acid (52) (3.00 g, 11.19 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (2.36 g, 12.31 mmol), 1-hydroxybenzotriazole (1.51 g, 11.17 mmol) and dimethylamine hydrochloride (912 mg, 11.19 mmol) in DMF (20 mL) was added triethylamine (4.7 mL, 25.83 mmol) resulting in the formation of a precipitate. The reaction was monitored by TLC (1:1 ethyl acetate, hexane). After 2 hours the argon purge needle was removed and additional dimethylamine hydrochloride added (0.3 eq). After a total of 20 hours, TLC revealed complete consumption of starting material. The reaction was diluted with water (40 mL) and ethyl acetate (40 mL). The reaction was transferred to a separatory funnel and the product was extracted into the organic layer. The organic layer was extracted again with water (20 mL) to remove the DMF, followed by 2 N NaOH (20 mL) and brine (15 mL). The yellow organic layer was dried over magnesium sulfate, filtered and concentrated to afford a white-pink solid. The product was purified by silica gel column chromatography (9:1 Ethyl acetate/hexanes) Yield: 1.407 g pure, compound 53, 1H NMR (DMSO) δ 11.00 (br s, NH), 7.68-7.67 (d, 1H, J=1.5), 7.31-7.28 (d, 1H, J=8.4 Hz), 7.72-7.14 (td, 2H, J=1.8, 8.4 Hz), 2.93-2.81 (m, 8 H), 2.64-2.59 (t, J=7.5 Hz, 2H).

Workup

  1. customTo a 250 mL argon purged round bottom flask fitted with a magnetic stirbar
  2. customresulting in the formation of a precipitate
  3. customAfter 2 hours the argon purge needle
  4. customwas removed
  5. additionadditional dimethylamine hydrochloride added (0.3 eq)
  6. customAfter a total of 20 hours, TLC
  7. customconsumption of starting material
  8. additionThe reaction was diluted with water (40 mL) and ethyl acetate (40 mL)
  9. customThe reaction was transferred to a separatory funnel
  10. extractionthe product was extracted into the organic layer
  11. extractionThe organic layer was extracted again with water (20 mL)
  12. customto remove the DMF
  13. dry with materialThe yellow organic layer was dried over magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customto afford a white-pink solid
  17. customThe product was purified by silica gel column chromatography (9:1 Ethyl acetate/hexanes) Yield: 1.407 g pure

Sources & evidence

ORD record
ord-38fbcb9cd0214a14892d4bf052047484
Source dataset
uspto-grants-2013_11
Patent number
US08586620B2

Reaction notes

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