Tyramine → di-(2-Chloroethyl)amino4-hydroxyphenethyl(methyl)aminomethanone

HRID 351134

Reaktionsgleichung

Reaktionsgleichung von HRID 351134
Cl.[Cl:2][CH2:3][CH2:4][NH:5][CH2:6][CH2:7][Cl:8].C([N:11]([CH2:14]C)[CH2:12][CH3:13])C.ClC([O:19]C)=S.ClCCNCCCl.NC[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([OH:37])=[CH:33][CH:32]=1>ClCCl.C(OCC)(=O)C>[Cl:2][CH2:3][CH2:4][N:5]([N:11]([C:12]([CH2:13][CH2:30][C:31]1[CH:36]=[CH:35][C:34]([OH:37])=[CH:33][CH:32]=1)=[O:19])[CH3:14])[CH2:6][CH2:7][Cl:8]

Komponenten

8

Edukt 5

HCID 5610TyramineHCID 8471TriethylamineHCID 9533Bis(2-chloroethyl)amineHCID 522769Bis(2-chloroethyl)amine hydrochlorideHCID 554404Methyl chloromethanethioate

Produkt 1

HCID 69423149di-(2-Chloroethyl)amino4-hydroxyphenethyl(methyl)aminomethanoneAusbeute 19,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

bis-(2-Chloroethyl)amine hydrochloride 26 (200 mg, 1.1 mmol) was dissolved in dichloromethane (15 mL) and triethylamine (0.45 mL, 3.3 mmol) was added. The mixture was stirred for 5 minutes at ambient temperature and methyl chlorothioformate (1.32 mmol) was added. The mixture was stirred until no bis-(2-chloroethyl)amine remained by TLC (ethyl acetate). N-mehty tyramine (322 mg, 2.1 mmol) was added and the mixture was heated under reflux for 4 hours. The mixture was allowed to cool, purified by dry flash column chromatography (silica gel, dichloromethane 200 mL) and concentrated in vacuo to yield prodrug 29 as an orange/brown oil (68 mg, 18%). νmax 3400, 1660, 1444, 1380, 1145/cm−1; δ 1H (400 MHz, CDCl3) 2.32 (3H, s, CH3) 2.60 (2H, t, J 3.72 Hz, 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), 43.3 (CH2), 44.1 (CH2), 44.2 (CH2), 45.2 (CH2), 46.5 (CH3) 46.6 (CH2), 115.9 (2×CH), 130 (2×CH), 130.1 (C), 155.6 (C), 161.5 (C). m/z (Cl) 283 (87%), 238 (50) 152 (100), 121 (45), 108 (35).

Aufarbeitung

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 4 hours
  3. temperatureto cool
  4. custompurified
  5. dry with materialby dry flash column chromatography (silica gel, dichloromethane 200 mL)
  6. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-9997450ebd0a49618ad905f90a8c0a4d
Quelldatensatz
uspto-grants-2007_02
Patentnummer
US07183319B2

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