Hydrochloric Acid → HCID 69296658, compound

HRID 2054594Notes

Reaction equation

HRID 2054594 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[C:11](=[O:17])[CH2:12][CH2:13][C:14]([OH:16])=[O:15].[H-].[Na+].[CH3:20][N:21]([CH3:32])[C:22]1[N:27]=[C:26]([N:28]([CH3:30])[CH3:29])[N:25]=[C:24](Cl)[N:23]=1.Cl>CN(C)C=O.O>[CH3:29][N:28]([CH3:30])[C:26]1[N:27]=[C:22]([N:21]([CH3:32])[CH3:20])[N:23]=[C:24]([N:7]2[C:8]3[C:4](=[CH:3][C:2]([Br:1])=[CH:10][CH:9]=3)[C:5]([C:11](=[O:17])[CH2:12][CH2:13][C:14]([OH:16])=[O:15])=[CH:6]2)[N:25]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 5415186-Chloro-N~2~,N~2~,N~4~,N~4~-tetramethyl-1,3,5-triazine-2,4-diamineHCID 43152055HCID 43152055, compound

Product 1

HCID 69296658HCID 69296658, compoundYield 48.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Conditions

Temperature
70 °C

Procedure

A solution of 4-(5-bromo-1H-indol-3-yl)-4-oxobutyric acid (148 mg, 0.5 mmol) in anhydrous dimethylformamide (5 mL) was added dropwise to a stirred suspension of sodium hydride (95%, 50 mg, 2.0 mmol) in dimethylformamide (5 mL). After 30 mins, a solution of N2,N2,N4,N4-tetramethyl-6-chloro-[1,3,5]-triazine-2,4-diamine (100 mg, 0.5 mmol) in dimethylformamide (5 mL) was added dropwise. The reaction mixture was stirred at 70° C. for 16 hours, cooled to room temperature and then poured carefully into water (20 mL), acidified to pH 4 with 0.5N hydrochloric acid and extracted with ethyl acetate (3×25 mL). The combined extract was washed with water, brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo. Purification by flash column chromatography (5% methanol in dichloromethane) afforded the title compound as a white solid (111 mg, 48%), Rf: 0.40 (10% methanol in dichloromethane); 1H NMR (DMSO-d6, 300 MHz) δ 8.96 (1H, s, ArH), 8.55 (1H, d, J=9 Hz, ArH), 8.33 (1H, d, J=2 Hz, ArH), 7.47 (1H, dd, J=9, 2 Hz, ArH), 3.22 (2H, t, J=7 Hz, CH2), 3.18 (6H, s, 2×Me), 3.12 (6H, s, 2×Me), 2.59 (2H, t, J=7 Hz, CH2); ESI-LCMS e/z calculated for C19H21BrN6O3 461.318, found 461 [M+H (79Br)]+, 463 [M+H (81Br)]+, 483 [M+Na (79Br)]+, 485 [M+Na (81Br)]+.

Workup

  1. temperaturecooled to room temperature
  2. extractionextracted with ethyl acetate (3×25 mL)
  3. extractionThe combined extract
  4. washwas washed with water, brine
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by flash column chromatography (5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-df004659aa674352ba22a0e45a38113e
Source dataset
uspto-grants-2008_02
Patent number
US07329680B2

Reaction notes

Loading…