Triethylamine → Methyl-2-di(2chloroethyl)aminocarbonylamino-3-(4-hydroxyphenyl)proponoate

HRID 351135

반응식

HRID 351135 반응식
Cl.[Cl:2][CH2:3][CH2:4][NH:5][CH2:6][CH2:7][Cl:8].C(N(CC)CC)C.Cl[C:17]([O:19]C)=S.ClCCNCCCl.[CH3:28][O:29][C:30](=[O:41])[C@H:31]([CH2:33][C:34]1[CH:39]=[CH:38][C:37]([OH:40])=[CH:36][CH:35]=1)[NH2:32]>ClCCl.C(OCC)(=O)C>[CH3:28][O:29][C:30](=[O:41])[CH:31]([NH:32][C:17]([N:5]([CH2:6][CH2:7][Cl:8])[CH2:4][CH2:3][Cl:2])=[O:19])[CH2:33][C:34]1[CH:35]=[CH:36][C:37]([OH:40])=[CH:38][CH:39]=1

참가 물질

8

반응물 5

HCID 8471TriethylamineHCID 9533Bis(2-chloroethyl)amineHCID 70652Tyrosine Methyl EsterHCID 522769Bis(2-chloroethyl)amine hydrochlorideHCID 554404Methyl chloromethanethioate

생성물 1

HCID 85794014Methyl-2-di(2chloroethyl)aminocarbonylamino-3-(4-hydroxyphenyl)proponoate수율 69.6%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

실험 절차

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). Tyrosine methyl ester (411 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 30 as an orange/brown oil (278 mg, 60%). νmax 3400, 1740, 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), 2.64 (3H, s, CH3) 3.12–3.25 (9H, m, ArCH2CH, 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) 29.8 (CH2), 43.3 (CH2), 44.1 (CH2), 44.2 (CH2), 45.2 (CH2), 46.6 (CH2), 47.1 (CH3) 115.9 (2×CH), 130 (2×CH), 130.1 (C), 155.6 (C), 160.3 (C) 161.5 (C). m/z (Cl) 242 (72%), 227 (45), 183 (75) 152 (100), 121 (45), 108 (35).

후처리

  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

출처 및 근거

ORD 기록
ord-a8b09987c2ab4f76bf510fab36999a78
출처 데이터셋
uspto-grants-2007_02
특허 번호
US07183319B2

연결된 노트

불러오는 중…