Veratrylamine → 2-Chloro-N-(3,4-dimethoxybenzyl)-5-(3,5-dimethylphenyl)nicotinamide

HRID 1675937Notes

Reaction equation

HRID 1675937 reaction equation
[Cl:1][C:2]1[N:10]=[CH:9][C:8]([C:11]2[CH:16]=[C:15]([CH3:17])[CH:14]=[C:13]([CH3:18])[CH:12]=2)=[CH:7][C:3]=1[C:4]([OH:6])=O.[CH3:19][O:20][C:21]1[CH:22]=[C:23]([CH:26]=[CH:27][C:28]=1[O:29][CH3:30])[CH2:24][NH2:25].F[P-](F)(F)(F)(F)F.ClC(=[N+]1CCCC1)N1CCCC1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[Cl:1][C:2]1[N:10]=[CH:9][C:8]([C:11]2[CH:16]=[C:15]([CH3:17])[CH:14]=[C:13]([CH3:18])[CH:12]=2)=[CH:7][C:3]=1[C:4]([NH:25][CH2:24][C:23]1[CH:26]=[CH:27][C:28]([O:29][CH3:30])=[C:21]([O:20][CH3:19])[CH:22]=1)=[O:6]

Participants

6

Reactant 4

HCID 79832VeratrylamineHCID 81531DiisopropylethylamineHCID 27366521-(Chloro-1-pyrrolidinylmethylene)pyrrolidinium HexafluorophosphateHCID 532227192-Chloro-5-(3,5-dimethylphenyl)nicotinic acid

Product 1

HCID 585390332-Chloro-N-(3,4-dimethoxybenzyl)-5-(3,5-dimethylphenyl)nicotinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of 2-chloro-5-(3,5-dimethylphenyl)nicotinic acid (1-2, 0.200 g, 0.764 mmol, 1 equiv) and 3,4-dimethoxybenzylamine (0.319g, 1.91 mmol, 2.50 equiv) in DMF (5 mL) was added 1-(chloro-1-pyrrolidinylmethylene)-pyrrolidinium hexafluorophosphate (PyClu, 0.383 mg, 1.15 mmol, 1.51 equiv), and diisopropylethylamine (0.667 mL, 3.82 mmol, 5.00 equiv). The resulting mixture was stirred at 23° C. for 20 hours. The reaction mixture was filtered and purified via reverse phase liquid chromatography (H2O/CH3CN gradient w/0.1% TFA present). The desired fractions were partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate (2×50 mL). The combined organic layers were washed with brine then dried over sodium sulfate and concentrated to give 2-chloro-N-(3,4-dimethoxybenzyl)-5-(3,5-dimethylphenyl)nicotinamide (1-3) as a white powder. LRMS m/z (M+H) 262.3 found, 262.1 required.

Workup

  1. filtrationThe reaction mixture was filtered
  2. custompurified via reverse phase liquid chromatography (H2O/CH3CN gradient w/0.1% TFA present)
  3. customThe desired fractions were partitioned between saturated aqueous sodium bicarbonate solution and ethyl acetate (2×50 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialthen dried over sodium sulfate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-178b94cecd2e4acf83cc76c9de739989
Source dataset
uspto-grants-2011_08
Patent number
US08003797B2

Reaction notes

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