Pyridine → Ethyl 2-(3-(4-methoxyphenylamino)-3-oxopropanamido)-2-methyl-4-oxo-4-p-tolylbutanoate

HRID 1629786Notes

Reaction equation

HRID 1629786 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:15])[CH2:11][C:12]([OH:14])=O)=[CH:5][CH:4]=1.ClC(N(C)C)=C(C)C.[NH2:24][C:25]([CH3:41])([CH2:31][C:32](=[O:40])[C:33]1[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][CH:34]=1)[C:26]([O:28][CH2:29][CH3:30])=[O:27].N1C=CC=CC=1>C(Cl)Cl.CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([NH:9][C:10](=[O:15])[CH2:11][C:12]([NH:24][C:25]([CH3:41])([CH2:31][C:32](=[O:40])[C:33]2[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][CH:34]=2)[C:26]([O:28][CH2:29][CH3:30])=[O:27])=[O:14])=[CH:7][CH:8]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 116585393-(4-Methoxyanilino)-3-oxopropanoic acidHCID 86685876Ethyl 2-amino-2-methyl-4-oxo-4-p-tolylbutanoate

Product 1

HCID 86685878Ethyl 2-(3-(4-methoxyphenylamino)-3-oxopropanamido)-2-methyl-4-oxo-4-p-tolylbutanoateYield 88%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of Intermediate 6B (0.388 g, 1.855 mmol) in DCM (10 mL) under argon was added 1-chloro-N,N,2-trimethylprop-1-en-1-amine (0.293 g, 2.192 mmol) and the reaction mixture was stirred at rt for 20 min. A solution of Intermediate 102B (0.4204 g, 1.686 mmol) in DCM (1.000 mL) followed by pyridine (0.409 mL, 5.06 mmol) were added and the reaction mixture was stirred at rt for 2.5 h. The reaction mixture was concentrated to give a dark oil which was dissolved in EtOAc (15 mL) and washed with water (5 mL). The organic phase was dried over MgSO4, filtered, and concentrated. The residue was purified by silica gel chromatography (80 g silica gel) to provide the desired product (0.650 g, 88%) as an orange oil. LCMS Anal. Calc'd for C24H28N2O6 440.19, found [M+H] 441.2. 1H NMR (500 MHz, CDCl3) δ 7.83 (d, J=8.25 Hz, 2H), 7.24 (d, J=7.98 Hz, 2H), 4.14 (dd, J=7.15, 2.75 Hz, 2H), 3.65 (d, J=17.61 Hz, 1H), 3.20 (d, J=17.61 Hz, 1H), 2.40 (s, 3H), 2.18-2.27 (m, 2H), 1.39 (s, 3H), 1.19 (t, J=7.01 Hz, 3H).

Workup

  1. additionwere added
  2. stirringthe reaction mixture was stirred at rt for 2.5 h
  3. concentrationThe reaction mixture was concentrated
  4. customto give a dark oil which
  5. washwashed with water (5 mL)
  6. dry with materialThe organic phase was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography (80 g silica gel)

Sources & evidence

ORD record
ord-9361725ad8e14fada796a39538ec69d0
Source dataset
uspto-grants-2014_07
Patent number
US08791091B2

Reaction notes

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