Ethyl orthoformate → 2-cyano-N-(2,4-dichloro-5-methoxyphenyl)-3-{4-methoxy-3-[3-(4-methylpiperazin-1-yl)-propoxy]-phenylamino}-acrylamide

HRID 1593787

Reaktionsgleichung

Reaktionsgleichung von HRID 1593787
[C:1]([CH2:3][C:4]([NH:6][C:7]1[CH:12]=[C:11]([O:13][CH3:14])[C:10]([Cl:15])=[CH:9][C:8]=1[Cl:16])=[O:5])#[N:2].[CH2:17](OC(OCC)OCC)C.[CH3:27][O:28][C:29]1[CH:34]=[CH:33][C:32]([NH2:35])=[CH:31][C:30]=1[O:36][CH2:37][CH2:38][CH2:39][N:40]1[CH2:45][CH2:44][N:43]([CH3:46])[CH2:42][CH2:41]1>C(O)(C)C>[C:1]([C:3](=[CH:17][NH:35][C:32]1[CH:33]=[CH:34][C:29]([O:28][CH3:27])=[C:30]([O:36][CH2:37][CH2:38][CH2:39][N:40]2[CH2:45][CH2:44][N:43]([CH3:46])[CH2:42][CH2:41]2)[CH:31]=1)[C:4]([NH:6][C:7]1[CH:12]=[C:11]([O:13][CH3:14])[C:10]([Cl:15])=[CH:9][C:8]=1[Cl:16])=[O:5])#[N:2]

Komponenten

5

Edukt 3

HCID 31214Ethyl orthoformateHCID 160991782-cyano-N-(2,4-dichloro-5-methoxyphenyl)acetamideHCID 589997944-Methoxy-3-[3-(4-methylpiperazin-1-yl)propoxy]aniline

Produkt 1

HCID 693108472-cyano-N-(2,4-dichloro-5-methoxyphenyl)-3-{4-methoxy-3-[3-(4-methylpiperazin-1-yl)-propoxy]-phenylamino}-acrylamideAusbeute 93 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3776IsopropanolLösungsmittel2×

Versuchsvorschrift

To a suspension of 2-cyano-N-(2,4-dichloro-5-methoxyphenyl)acetamide (1.75 g, 6.75 mmol) in 8.2 mL of iso-propanol was added triethylorthoformate (1.5 g, 10.1 mmol). The mixture was heated to reflux. After 20 minutes, 4-methoxy-3-[3-(4-methyl-piperazin-1-yl)-propoxy]-phenylamine in 20 mLs of iso-propanol was added dropwise so as to maintain reflux. After 26 hours, the reaction was cooled to room temperature and the suspended solids were filtered. The solids were rinsed with iso-propanol until effluent was colorless. The yellow solid was dried in vacuo to give 3.45 g (93%) of 2-cyano-N-(2,4-dichloro-5-methoxyphenyl)-3-{4-methoxy-3-[3-(4-methylpiperazin-1-yl)-propoxy]-phenylamino}-acrylamide as a mixture of isomers. 1H NMR (300 MHz, CDCl3) δ 11.35 (br d, 1H), 8.17 (m, 2H), 7.76 (d, 1H), 7.41 (s, 1H), 6.88 (m, 1H) 6.69 (m, 2H), 4.10 (t, J=7 Hz, 2H), 3.96 (s, 3H), 3.87 (s, 3), 2.55 (t, J=7 Hz, 2H), 2.48 (m, 8H), 2.29 (s, 3H), 2.06 (m, 2H); MS (ES) m/z548.1 (M+)

Aufarbeitung

  1. temperatureThe mixture was heated to reflux
  2. temperatureto maintain
  3. temperaturereflux
  4. waitAfter 26 hours
  5. filtrationthe suspended solids were filtered
  6. washThe solids were rinsed with iso-propanol until effluent
  7. customThe yellow solid was dried in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-fc9bbdfc89d94943949400054f3b3c39
Quelldatensatz
uspto-grants-2007_11
Patentnummer
US07297795B2

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