Triethylamine → 1,5-Dimethyl-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid (4-benzylamino-6-morpholin-4-yl-pyridin-3-yl)-amide

HRID 930526Notes

Reaction equation

HRID 930526 reaction equation
[CH3:1][N:2]1[C:7](=[O:8])[C:6]([CH3:9])=[CH:5][C:4]([C:10]([OH:12])=O)=[CH:3]1.[CH2:13]([NH:20][C:21]1[CH:26]=[C:25]([N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)[N:24]=[CH:23][C:22]=1[NH2:33])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(N(CC)CC)C>C1COCC1>[CH2:13]([NH:20][C:21]1[CH:26]=[C:25]([N:27]2[CH2:28][CH2:29][O:30][CH2:31][CH2:32]2)[N:24]=[CH:23][C:22]=1[NH:33][C:10]([C:4]1[CH:5]=[C:6]([CH3:9])[C:7](=[O:8])[N:2]([CH3:1])[CH:3]=1)=[O:12])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 218859251,5-Dimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acidHCID 117892051N4-Benzyl-6-morpholin-4-yl-pyridine-3,4-diamine

Product 1

HCID 1178940391,5-Dimethyl-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid (4-benzylamino-6-morpholin-4-yl-pyridin-3-yl)-amide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N-Propylphosphonic acid anhydride, cyclic trimer (0.356 ml; 0.610 mmol) is added to a mixture of 1,5-dimethyl-6-oxo-1,6-dihydro-pyridine-3-carboxylic acid D1 (85.000 mg; 0.508 mmol), N4-Benzyl-6-morpholin-4-yl-pyridine-3,4-diamine E-2.3 (133.000 mg; 0.468 mmol) and triethylamine (0.176 ml; 1.271 mmol) in THF (3.000 ml). The reaction mixture is stirred overnight (16 h) at RT. The reaction is quenched with 1M NaOH (2 ml) and diluted with water, then extracted twice with ethyl acetate. The organic layer is dried over Na2SO4 and concentrated in vacuum. The residue is purified on silica chromatography Combiflash (Column: Redisep Rf, 12 g; gradient: DCM/MeOH=100%/0% to 90%/10%; flow rate=30 ml/min; 28 column volumes; detection wavelength: 254 nm). The product containing fractions are combined and concentrated under reduce pressure.

Workup

  1. customThe reaction is quenched with 1M NaOH (2 ml)
  2. additiondiluted with water
  3. extractionextracted twice with ethyl acetate
  4. dry with materialThe organic layer is dried over Na2SO4
  5. concentrationconcentrated in vacuum
  6. customThe residue is purified on silica chromatography Combiflash (Column: Redisep Rf, 12 g; gradient: DCM/MeOH=100%/0% to 90%/10%; flow rate=30 ml/min; 28 column volumes; detection wavelength: 254 nm)
  7. additionThe product containing fractions
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-e4382a4f11e143b3b8db53faf5300f66
Source dataset
uspto-grants-2016_03
Patent number
US09296748B2

Reaction notes

Loading…