Diisopropylethylamine → 2-(4-{4-[(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)amino]-5-methoxy-2-nitrophenyl}piperazin-1-yl)-N,N-dimethylacetamide

HRID 1842717

反応式

HRID 1842717 の反応式
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][N:40]([CH3:50])[C:41](=[O:49])[CH2:42][N:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1>FC(F)(F)CO>[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[C:19]([O:28][CH3:29])=[CH:20][C:21]([N:46]3[CH2:45][CH2:44][N:43]([CH2:42][C:41]([N:40]([CH3:50])[CH3:39])=[O:49])[CH2:48][CH2:47]3)=[C:22]([N+:24]([O-:26])=[O:25])[CH:23]=2)=[N:15][CH:16]=1

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 2758642N,N-dimethyl-2-(piperazin-1-yl)acetamideHCID 712393485-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine2 回

生成物 1

HCID 712407892-(4-{4-[(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)amino]-5-methoxy-2-nitrophenyl}piperazin-1-yl)-N,N-dimethylacetamide収率 83%

試薬・触媒・溶媒 1

HCID 64092,2,2-Trifluoroethanol溶媒

反応条件

温度
140 °C

実験手順

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, 207 mg, 0.5 mmol) and N,N-dimethyl-2-piperazin-1-ylacetamide (86 mg, 0.50 mmol) in 2,2,2-trifluoroethanol (2.5 mL). The mixture was heated in a microwave at 140° C. for 1 h then cooled to r.t. The mixture was purified directly by ion exchange chromatography, using an SCX column and eluting with 7M methanolic ammonia to provide crude product after concentration of appropriate fractions. Further purification by FCC, eluting with 0-5% CH3OH in CH2Cl2 gave the title compound (234 mg, 83%) as an orange foam; 1H NMR: (CDCl3) 2.71-2.78 (4H, m), 2.97 (3H, s), 3.09 (3H, s), 3.11-3.18 (4H, m), 3.26 (2H, s), 3.99 (3H, s), 6.66 (1H, s), 6.97 (1H, td), 7.35-7.42 (1H, m), 7.52 (1H, s), 8.41 (1H, s), 8.49 (1H, d), 8.56 (1H, d), 8.92 (1H, s), 9.02 (1H, s); m/z: ES+ MH+ 566.52.

後処理

  1. temperaturethen cooled to r.t
  2. customThe mixture was purified directly by ion exchange chromatography
  3. washeluting with 7M methanolic ammonia
  4. customto provide crude product after concentration of appropriate fractions
  5. customFurther purification by FCC
  6. washeluting with 0-5% CH3OH in CH2Cl2

出典と根拠

ORDレコード
ord-a55d8c16b2d444b493a7419950fd6f77
出典データセット
uspto-grants-2015_02
特許番号
US08946235B2

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