Triethylamine → 2-[2-(2,5-Dimethyl-phenyl)-acetyl]-5-methoxy-[1,2,5]triazepane-1-carboxylic acid ethyl ester

HRID 924604Notes

Reaction equation

HRID 924604 reaction equation
Cl.[CH2:2]([O:4][C:5]([N:7]1[CH2:13][CH2:12][N:11]([O:14][CH3:15])[CH2:10][CH2:9][NH:8]1)=[O:6])[CH3:3].C(N(CC)CC)C.[CH3:23][C:24]1[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][C:25]=1[CH2:31][C:32](Cl)=[O:33]>CN(C)C1C=CN=CC=1.O1CCCC1>[CH2:2]([O:4][C:5]([N:7]1[CH2:13][CH2:12][N:11]([O:14][CH3:15])[CH2:10][CH2:9][N:8]1[C:32](=[O:33])[CH2:31][C:25]1[CH:26]=[C:27]([CH3:30])[CH:28]=[CH:29][C:24]=1[CH3:23])=[O:6])[CH3:3]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 22561615(2,5-Dimethylphenyl)acetyl chlorideHCID 867199195-Methoxy-[1,2,5]triazepane-1-carboxylic acid ethyl ester hydrochloride salt

Product 1

HCID 867199182-[2-(2,5-Dimethyl-phenyl)-acetyl]-5-methoxy-[1,2,5]triazepane-1-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
2.5 °C

Procedure

To a solution of 5-methoxy-[1,2,5]triazepane-1-carboxylic acid ethyl ester hydrochloride salt (1.33 g, 4.84 mmol), triethylamine (1.68 ml, 1.22 g, 12.07 mmol) and a catalytic amount of 4-dimethylaminopyridine in tetrahydrofuran (20 ml) at 0-5° C. was added a solution of (2,5-dimethyl-phenyl)-acetyl chloride (0.93 g, 5.09 mmol) in tetrahydrofuran (5 ml) dropwise. The suspension was stirred at 0-5° C. for one hour, and at room temperature for 4 hours. The solvent was evaporated, the residue diluted with ethyl acetate (50 ml) and water (20 ml), the layers separated and the aqueous phase extracted with ethyl acetate (2×25 ml). The combined organic layers were washed with water (2×20 ml) and brine (20 ml), dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate 2:1). Yield: 1.1 g of 2-[2-(2,5-dimethyl-phenyl)-acetyl]-5-methoxy-[1,2,5]triazepane-1-carboxylic acid ethyl ester (compound P3.3) as a viscous oil. 1H-NMR (400 MHz, CD3OD): δ 1.14-1.39 (br m, 3H), 2.18 (s, 3H), 2.26 (s, 3H), 2.83-3.09 (br m, 4H), 3.13-3.32 (br m, 2H), 3.48 (s, 3H), 3.62 (br s, 2H), 3.78-4.32 (br m, overlapping signals, total 4H), 6.91 (s, 1H), 6.95 (d, J=7.8 Hz, 1H), 7.03 (d, J=7.8 Hz, 1H) ppm.

Workup

  1. waitat room temperature for 4 hours
  2. customThe solvent was evaporated
  3. additionthe residue diluted with ethyl acetate (50 ml) and water (20 ml)
  4. customthe layers separated
  5. extractionthe aqueous phase extracted with ethyl acetate (2×25 ml)
  6. washThe combined organic layers were washed with water (2×20 ml) and brine (20 ml)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate 2:1)

Sources & evidence

ORD record
ord-e380b1e375d0458182d6a2a0d5d85cd1
Source dataset
uspto-grants-2016_03
Patent number
US09282743B2

Reaction notes

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