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

HRID 1593787노트

반응식

HRID 1593787 반응식
[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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 3776Isopropanol용매2회

실험 절차

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+)

후처리

  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

출처 및 근거

ORD 기록
ord-fc9bbdfc89d94943949400054f3b3c39
출처 데이터셋
uspto-grants-2007_11
특허 번호
US07297795B2

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