Diisopropylethylamine → (R)-tert-butyl 4-((2-bromo-7-carbamoylimidazo[1,2-b]pyridazin-8-yl)amino)-3,3-dimethylpiperidine-1-carboxylate

HRID 1487328ノート

反応式

HRID 1487328 の反応式
[Br:1][C:2]1[N:3]=[C:4]2[C:9](Cl)=[C:8]([C:11]([NH2:13])=[O:12])[CH:7]=[N:6][N:5]2[CH:14]=1.[NH2:15][C@@H:16]1[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][C:17]1([CH3:30])[CH3:29].CCN(C(C)C)C(C)C>CN(C=O)C>[Br:1][C:2]1[N:3]=[C:4]2[C:9]([NH:15][C@@H:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][C:17]3([CH3:30])[CH3:29])=[C:8]([C:11](=[O:12])[NH2:13])[CH:7]=[N:6][N:5]2[CH:14]=1

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 68945318(R)-Tert-butyl 4-amino-3,3-dimethylpiperidine-1-carboxylateHCID 899954732-Bromo-8-chloro-imidazo[1,2-b]pyridazine-7-carboxamide

生成物 1

HCID 89995471(R)-tert-butyl 4-((2-bromo-7-carbamoylimidazo[1,2-b]pyridazin-8-yl)amino)-3,3-dimethylpiperidine-1-carboxylate収率 88.5%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
90 °C

実験手順

To a solution of 2-bromo-8-chloroimidazo[1,2-b]pyridazine-7-carboxamide (170 mg, 0.617 mmol) and (R)-tert-butyl 4-amino-3,3-dimethylpiperidine-1-carboxylate (144 mg, 0.633 mmol) in DMF (1543 μl) was added DIEA (237 μl, 1.358 mmol). The reaction was heated at 90° C. for 2 hours. After cooling to room temperature, the reaction mixture was partitioned between water and ethyl acetate (100 ml). The ethyl acetate layer was washed with water (3×100 ml), dried with sodium sulfate, filtered, and concentrated under reduced pressure. The crude solid was purified via flash chromatography (ISCO silica gel column, 0-10% MeOH-DCM) to afford (R)-tert-butyl 4-((2-bromo-7-carbamoylimidazo[1,2-b]pyridazin-8-yl)amino)-3,3-dimethylpiperidine-1-carboxylate (255 mg, 0.546 mmol, 88% yield) as a faint yellow solid. ESI-MS (analytical LCMS Method A): m/z 467.0 ([M+H]+). HPLC (analytical HPLC Method A) Rt: 3.413 min.

後処理

  1. temperatureAfter cooling to room temperature
  2. customthe reaction mixture was partitioned between water and ethyl acetate (100 ml)
  3. washThe ethyl acetate layer was washed with water (3×100 ml)
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude solid was purified via flash chromatography (ISCO silica gel column, 0-10% MeOH-DCM)

出典と根拠

ORDレコード
ord-7c640fddc5b544929ceef4c15469be55
出典データセット
uspto-grants-2016_08
特許番号
US09428511B2

反応ノート

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