Tyramine → bis-(2-Chloroethyl)amino-4-hydroxyphenylaminomethanone

HRID 351132Notes

Reaction equation

HRID 351132 reaction equation
[Cl:1][CH2:2][CH2:3][N:4]([C:8]([O:10]C1C=CC([N+]([O-])=O)=CC=1)=O)[CH2:5][CH2:6][Cl:7].C([N:22](CC)CC)C.NCC[C:30]1[CH:35]=[CH:34][C:33]([OH:36])=[CH:32][CH:31]=1>CN(C)C=O>[Cl:1][CH2:2][CH2:3][N:4]([C:8]([NH:22][C:30]1[CH:31]=[CH:32][C:33]([OH:36])=[CH:34][CH:35]=1)=[O:10])[CH2:5][CH2:6][Cl:7]

Participants

5

Reactant 3

HCID 5610TyramineHCID 8471TriethylamineHCID 21091238HCID 21091238, compound

Product 1

HCID 21091234bis-(2-Chloroethyl)amino-4-hydroxyphenylaminomethanoneYield 73.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

27 (860 mg, 2.8 mmol) was dissolved in dimethylformamide (20 mL) and triethylamine (0.9 mL, 5.6 mmol) was added. The mixture was stirred at reflux for 30 minutes and tyramine (0.76 mg, 5.6 mmol) was added. The mixture was heated under reflux for a further 6 hours and then concentrated in vacuo. Purification by column chromatography (silica gel, dichloromethane then methanol) gave prodrug 28 as an orange/brown oil (571 mg, 67%). νmax 3400, 1660, 1444, 1380, 1145/cm−1; δ 1H (400 MHz, CDCl3) 2.61 (2H, t, J 3.72 Hz, 4,CH2Ar), 3.17–3.22 (10H, m, ArCH2CH2, 2×CH2CH2Cl), 6.67 (2H, d, J 5.7 Hz, 2×ArH), 6.9 (2H, d, J 5.7 Hz, 2×ArH), 7.82 (1H, brs, NH); 13C (100 MHz, CDCl3), 30.1 (CH2), 43.1 (CH2), 43.4 (CH2), 44.2 (CH2), 46.2 (CH2), 46.7 (CH2), 115.9 (2×CH), 130 (2×CH), 130.1 (C), 155.6 (C), 161.5 (C). m/z (Cl) 269 (87%), 224 (50), 138 (100), 121 (45), 108 (35).

Workup

  1. temperatureat reflux for 30 minutes
  2. temperatureThe mixture was heated
  3. temperatureunder reflux for a further 6 hours
  4. concentrationconcentrated in vacuo
  5. customPurification by column chromatography (silica gel, dichloromethane

Sources & evidence

ORD record
ord-a71cd880610b44c88f22b0347a7adb5c
Source dataset
uspto-grants-2007_02
Patent number
US07183319B2

Reaction notes

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