Diisopropylethylamine → N-(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-2-methoxy-N'-methyl-N'-(2-(4-methylpiperazin-1-yl)ethyl]-5-nitrobenzene-1,4-diamine

HRID 1842762

반응식

HRID 1842762 반응식
CCN(C(C)C)C(C)C.[Cl:10][C:11]1[C:12]([C:30]2[CH:31]=[N:32][N:33]3[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=23)=[N:13][C:14]([NH:17][C:18]2[CH:23]=[C:22]([N+:24]([O-:26])=[O:25])[C:21](F)=[CH:20][C:19]=2[O:28][CH3:29])=[N:15][CH:16]=1.[CH3:39][NH:40][CH2:41][CH2:42][N:43]1[CH2:48][CH2:47][N:46]([CH3:49])[CH2:45][CH2:44]1>CC(N(C)C)=O>[Cl:10][C:11]1[C:12]([C:30]2[CH:31]=[N:32][N:33]3[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=23)=[N:13][C:14]([NH:17][C:18]2[CH:23]=[C:22]([N+:24]([O-:26])=[O:25])[C:21]([N:40]([CH3:39])[CH2:41][CH2:42][N:43]3[CH2:48][CH2:47][N:46]([CH3:49])[CH2:45][CH2:44]3)=[CH:20][C:19]=2[O:28][CH3:29])=[N:15][CH:16]=1

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 14979290N-Methyl-2-(4-methylpiperazin-1-yl)ethan-1-amine3회HCID 712393485-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine2회

생성물 1

HCID 71240746N-(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)-2-methoxy-N'-methyl-N'-(2-(4-methylpiperazin-1-yl)ethyl]-5-nitrobenzene-1,4-diamine수율 67.4%

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

반응 조건

온도
140 °C

실험 절차

DIPEA (0.105 mL, 0.60 mmol) was added to a mixture of 5-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 20, 0.207 g, 0.5 mmol) and N-methyl-2-(4-methylpiperazin-1-yl)ethanamine (Intermediate 109, 0.079 g, 0.50 mmol) in DMA (5 mL). The mixture was heated in a microwave at 140° C. for 3 h. An additional portion of N-methyl-2-(4-methylpiperazin-1-yl)ethanamine (8 mg, 0.05 mmol) was added and the mixture was heated in a microwave at 140° C. for a further 1 h before being cooled to r.t. The mixture was then concentrated in vacuo and the residue was dissolved in CH3OH. Purification by ion exchange chromatography, using an SCX column and eluting with 1M methanolic ammonia provided crude material after concentration of appropriate fractions in vacuo. Further purification by FCC, eluting with 2-8% CH3OH in CH2Cl2 gave the title compound (0.186 g, 67%) as an orange foam; 1H NMR: (CDCl3) 2.26 (3H, s), 2.32-2.45 (4H, m), 2.45-2.57 (4H, m), 2.61 (2H, t), 2.89 (3H, s), 3.29 (2H, t), 3.98 (3H, s), 6.65 (1H, s), 6.93-7.00 (1H, m), 7.38 (1H, ddd), 7.44 (1H, s), 8.40 (1H, s), 8.49 (1H, d), 8.55 (1H, d), 8.91 (2H, d); m/z: ES+ MH+ 552.59.

후처리

  1. temperaturethe mixture was heated in a microwave at 140° C. for a further 1 h
  2. temperaturebefore being cooled to r.t
  3. concentrationThe mixture was then concentrated in vacuo
  4. dissolutionthe residue was dissolved in CH3OH
  5. customPurification by ion exchange chromatography
  6. washeluting with 1M methanolic ammonia
  7. customprovided crude material after concentration of appropriate fractions in vacuo
  8. customFurther purification by FCC
  9. washeluting with 2-8% CH3OH in CH2Cl2

출처 및 근거

ORD 기록
ord-61da6146b3b643aabc39ee47552bc3bb
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946235B2

연결된 노트

불러오는 중…