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Diisopropylethylamine → N-[4-[(3aR,6aR)-5-methyl-2,3,3a,4,6,6a-hexahydropyrrolo[3,2-c]pyrrol-1-yl]-2-methoxy-5-nitrophenyl]-5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine

HRID 1842699
ノート
印刷プレビュー

反応式

HRID 1842699 の反応式
[CH3:1][N:2]1[CH2:6][C@@H:5]2[NH:7][CH2:8][CH2:9][C@@H:4]2[CH2:3]1.[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.CCN(C(C)C)C(C)C>FC(F)(F)CO>[CH3:1][N:2]1[CH2:6][C@@H:5]2[N:7]([C:21]3[C:22]([N+:24]([O-:26])=[O:25])=[CH:23][C:18]([NH:17][C:14]4[N:13]=[C:12]([C:30]5[CH:31]=[N:32][N:33]6[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=56)[C:11]([Cl:10])=[CH:16][N:15]=4)=[C:19]([O:28][CH3:29])[CH:20]=3)[CH2:8][CH2:9][C@@H:4]2[CH2:3]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 44221716(3aR,6aR)-5-Methyloctahydropyrrolo[3,4-b]pyrrole2 回HCID 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 71270223N-[4-[(3aR,6aR)-5-methyl-2,3,3a,4,6,6a-hexahydropyrrolo[3,2-c]pyrrol-1-yl]-2-methoxy-5-nitrophenyl]-5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine収率 49.6%

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

(3aR,6aR)-5-Methyl-2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,2-c]pyrrole (Intermediate 37, 91 mg, 0.72 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, 250 mg, 0.60 mmol) and DIPEA (0.334 mL, 1.93 mmol) in 2,2,2-trifluoroethanol (3 mL) and the mixture was heated at 140° C. in a microwave for 0.5 h. The mixture was then absorbed onto silica. Purification by FCC, eluting with 2% 7N methnaolic ammonia in CH2Cl2 gave material that was concentrated in vacuo and dissolved in CH3OH. The resulting solution was absorbed onto an SCX column and the column was washed with CH3OH then eluted with 7N methanolic ammonia. Appropriate fractions were concentrated in vacuo to give the title compound (155 mg, 49%) as a orange/red gummy solid; 1H NMR: (CDCl3) 1.89 (1H, dd), 2.04-2.19 (1H, m), 2.24 (3H, s), 2.30-2.39 (1H, m), 2.40-2.57 (2H, m), 2.68 (1H, t), 2.98-3.11 (1H, m), 3.23 (1H, t), 3.51-3.63 (1H, m), 3.97 (3H, s), 4.36-4.48 (1H, m), 6.46 (1H, s), 6.90-7.02 (1H, m), 7.31-7.43 (2H, m), 8.38 (1H, s), 8.48 (1H, dd), 8.53-8.57 (1H, m), 8.82 (1H, s), 8.93 (1H, s); m/z: ES+ MH+ 521.45.

後処理

  1. customThe mixture was then absorbed onto silica
  2. customPurification by FCC
  3. washeluting with 2% 7N methnaolic ammonia in CH2Cl2
  4. customgave material that
  5. concentrationwas concentrated in vacuo
  6. dissolutiondissolved in CH3OH
  7. customThe resulting solution was absorbed onto an SCX column
  8. washthe column was washed with CH3OH
  9. washthen eluted with 7N methanolic ammonia
  10. concentrationAppropriate fractions were concentrated in vacuo

出典と根拠

ORDレコード
ord-f597bcdf3a204923bd9e9ed39b5a8790
出典データセット
uspto-grants-2015_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08946235B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート