Benzaldehyde → HCID 11653129, compound

HRID 2224700Notes

Reaction equation

HRID 2224700 reaction equation
[NH2:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]2[CH:19]=[CH:18][C:14]([C:15]([NH2:17])=[O:16])=[CH:13][N:12]=2)=[CH:6][CH:5]=1.[CH:20](=O)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>CO>[CH2:20]([NH:1][CH2:2][CH2:3][C:4]1[CH:5]=[CH:6][C:7]([NH:10][C:11]2[CH:19]=[CH:18][C:14]([C:15]([NH2:17])=[O:16])=[CH:13][N:12]=2)=[CH:8][CH:9]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

4

Reactant 2

HCID 240BenzaldehydeHCID 59717859HCID 59717859, compound

Product 1

HCID 11653129HCID 11653129, compoundYield 8.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Combine 6-[4-(2-amino-ethyl)-phenylamino]-nicotinamide (200 mg, 0.78 mmol) (step 2, Example 16), benzaldehyde (83 mg, 0.78 mmol), 3 Å molecular sieves (0.2 g), and methanol (10 mL) and stir overnight at room temperature. Filter off the sieves then add sodium borohydride (0.4 mg) to the reaction and stirred at room temperature for 4 hours. Add water (20 mL) then extract with dicholormethane (3×50 mL). Dry the dichloromethane extracts with sodium chloride/magnesium sulfate, filter, then concentrate on a rotary evaporator to yield 0.2 g of the crude product. The crude product is purified by flash column chromatography on silica gel eluting with 10% conc. ammonium hydroxide in ethanol and chloroform to yield 6-[4-(2-Benzylamino-ethyl)-phenylamino]-nicotinamide (24 mg): 1H NMR (MeOD, 300.00 MHz): 8.66 (d, 1H, J=1.8 Hz), 8.00 (dd, 1H, J=9.0, 2.4 Hz), 7.55-7.15 (m, 10H), 6.81 (d, 1H, J=8.8 Hz), 3.80 (s, 2H), 3.38 (m, 1H), 2.84 (m, 5H); m/z=347.01(M+1); HPLC=95% @ 5.54 minutes (5/95 to 95/5 ACN/(0.1% TFA in water) over 10 minutes, Zorbax SB-Phenyl 4.6 mm×15 cm×5 micron, λ=254 nM.

Workup

  1. filtrationFilter off the sieves
  2. customadd sodium borohydride (0.4 mg) to the reaction
  3. extractionAdd water (20 mL) then extract with dicholormethane (3×50 mL)
  4. dry with materialDry the dichloromethane
  5. filtrationfilter
  6. concentrationconcentrate on a rotary evaporator
  7. customto yield 0.2 g of the crude product
  8. customThe crude product is purified by flash column chromatography on silica gel eluting with 10% conc. ammonium hydroxide in ethanol and chloroform

Sources & evidence

ORD record
ord-64bc0ff0aa2c4381a374ff227a0b69a2
Source dataset
uspto-grants-2008_05
Patent number
US07378448B2

Reaction notes

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