Hydrochloric Acid → (R)-4-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-6-methoxy-N-(piperidin-3-yl)pyrimidin-2-amine

HRID 1529425ノート

反応式

HRID 1529425 の反応式
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[C:18]1[CH:23]=[C:22]([O:24][CH3:25])[N:21]=[C:20]([NH:26][C@@H:27]2[CH2:32][CH2:31][CH2:30][N:29](C(OC(C)(C)C)=O)[CH2:28]2)[N:19]=1.Cl>O1CCOCC1>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[C:18]1[CH:23]=[C:22]([O:24][CH3:25])[N:21]=[C:20]([NH:26][C@@H:27]2[CH2:32][CH2:31][CH2:30][NH:29][CH2:28]2)[N:19]=1

参加物

4

反応物 2

HCID 313Hydrochloric AcidHCID 67959910(R)-tert-butyl 3-((4-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)amino)piperidine-1-carboxylate

生成物 1

HCID 67959825(R)-4-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-6-methoxy-N-(piperidin-3-yl)pyrimidin-2-amine収率 22%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒2 回

反応条件

温度
90 °C

実験手順

To solution of (R)-tert-butyl 3-((4-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)amino)piperidine-1-carboxylate (130 mg, 0.243 mmol) in dioxane (2 mL) was added HCl in dioxane (4 M, 2 mL) and the mixture was heated at 90° C. for overnight. The reaction was quenched with aq.NaHCO3 and extracted with EtOAc. The organic layer was dried (Na2SO4), filtered and concentrated. The residue was washed with 50% EtOAc in petroleum ether to give (R)-4-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-6-methoxy-N-(piperidin-3-yl)pyrimidin-2-amine (22 mg, 22%). MS (ESI, pos. ion) m/z: 436.1 (M+1); 1H-NMR (400 MHz DMSO-d6): δ ppm: 11.78 (brs, 1H) 8.66 (s, 1H), 8.25 (s, 1H), 7.54 (d, J=8.4 Hz, 1H), 7.41-7.46 (m, 1H), 7.21-7.22 (m, 3H), 6.70 (s, 1H), 6.48 (s, 1H), 3.80-3.83 (brs, 4H), 2.89-2.99 (m, 1H), 2.33-2.41 (m, 2H), 1.98-1.99 (m, 2H), 1.43-1.50 (m, 2H), 1.12-1.24 (m, 2H).

後処理

  1. customThe reaction was quenched with aq
  2. extractionNaHCO3 and extracted with EtOAc
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. washThe residue was washed with 50% EtOAc in petroleum ether

出典と根拠

ORDレコード
ord-e90774d126fa47fcb47e3575745769b3
出典データセット
uspto-grants-2015_07
特許番号
US09090593B2

反応ノート

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