Triethylamine → N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,6-dimethyl-7-oxo-1-(1-phenylethyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-3-carboxamide

HRID 1526973Notes

Reaction equation

HRID 1526973 reaction equation
[CH3:1][C:2]1[N:12]([CH:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH3:14])[C:5]2[C:6](=[O:11])[N:7]([CH3:10])[CH:8]=[CH:9][C:4]=2[C:3]=1[C:21](O)=[O:22].N[CH2:25][C:26]1[CH:31]=[C:30]([CH3:32])[NH:29][C:28](=[O:33])[C:27]=1[CH3:34].C[N:36](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C)C=O>[CH3:25][C:26]1[CH:31]=[C:30]([CH3:32])[NH:29][C:28](=[O:33])[C:27]=1[CH2:34][NH:36][C:21]([C:3]1[C:4]2[CH:9]=[CH:8][N:7]([CH3:10])[C:6](=[O:11])[C:5]=2[N:12]([CH:13]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH3:14])[C:2]=1[CH3:1])=[O:22]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 897416144-(aminomethyl)-3,6-dimethylpyridin-2(1H)-oneHCID 897417742,6-dimethyl-7-oxo-1-(1-phenylethyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-3-carboxylic acid

Product 1

HCID 117778868N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,6-dimethyl-7-oxo-1-(1-phenylethyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-3-carboxamideYield 53%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 2,6-dimethyl-7-oxo-1-(1-phenylethyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-3-carboxylic acid (200 mg, 0.64 mmol) and 4-(aminomethyl)-3,6-dimethylpyridin-2(1H)-one (118 mg, 0.78 mmol) in N,N-dimethylformamide (20 mL) was added o-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (365 mg, 0.96 mmol) and triethylamine (388 mg, 3.84 mmol) at room temperature. The resultant mixture was stirred at room temperature for 2 hours. Once starting material left was consumed, the reaction mixture was quenched with water (50 mL), and extracted with ethyl acetate (50 mL*3). The combined organic layers were washed with brine (100 mL*2), dried over anhydrous sodium sulfate, filtered and concentrated to give a residue. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=1:2) to give N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2.6-dimethyl-7-oxo-1-(1-phenylethyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridine-3-carboxamide (150 mg, 53%) as a white solid. LRMS (M+H+) m/z: calcd 444.22. found 444. HPLC purity (214 nm): 97%. 1H NMR (400 MHz, CD3OD): δ 7.22-7.13 (m, 4H), 7.01 (d, J=7.2 Hz, 2H), 6.69 (d, J=7.2 Hz, 1H), 5.99 (s, 1H), 4.35 (s, 2H), 3.50-3.21 (m, 4H), 2.26 (s, 3H), 2.13 (s, 3H), 2.06 (s, 3H), 1.82 (d, J=7.2 Hz, 3H).

Workup

  1. waitOnce starting material left
  2. customwas consumed
  3. customthe reaction mixture was quenched with water (50 mL)
  4. extractionextracted with ethyl acetate (50 mL*3)
  5. washThe combined organic layers were washed with brine (100 mL*2)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a residue
  10. customThe residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=1:2)

Sources & evidence

ORD record
ord-25cc0be23ef547e48101786ee781dca2
Source dataset
uspto-grants-2015_07
Patent number
US09085583B2

Reaction notes

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