Sodium Iodide → 3-[6-(Azetidine-1-carbonyl)pyridin-3-yl]oxy-5-(1-cyclobutyl-2-oxo-pyrrolidin-3-yl)oxy-N-(5-methylpyrazin-2-yl)benzamide

HRID 600519ノート

反応式

HRID 600519 の反応式
[N:1]1([C:5]([C:7]2[N:12]=[CH:11][C:10]([O:13][C:14]3[CH:15]=[C:16]([CH:31]=[C:32]([C:34](=[O:43])[NH:35][C:36]4[CH:41]=[N:40][C:39]([CH3:42])=[CH:38][N:37]=4)[CH:33]=3)[O:17][CH:18]([CH2:24][CH2:25]OS(C)(=O)=O)[C:19]([O:21]CC)=O)=[CH:9][CH:8]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1.[I-].[Na+].[CH:46]1([NH2:50])[CH2:49][CH2:48][CH2:47]1>C(#N)C>[N:1]1([C:5]([C:7]2[N:12]=[CH:11][C:10]([O:13][C:14]3[CH:33]=[C:32]([CH:31]=[C:16]([O:17][CH:18]4[CH2:24][CH2:25][N:50]([CH:46]5[CH2:49][CH2:48][CH2:47]5)[C:19]4=[O:21])[CH:15]=3)[C:34]([NH:35][C:36]3[CH:41]=[N:40][C:39]([CH3:42])=[CH:38][N:37]=3)=[O:43])=[CH:9][CH:8]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1

参加物

5

反応物 3

HCID 5238Sodium IodideHCID 75645CyclobutylamineHCID 86621533Ethyl 2-[3-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(5-methylpyrazin-2-yl)carbamoyl]phenoxy]-4-methylsulfonyloxy-butanoate2 回

生成物 1

HCID 249530143-[6-(Azetidine-1-carbonyl)pyridin-3-yl]oxy-5-(1-cyclobutyl-2-oxo-pyrrolidin-3-yl)oxy-N-(5-methylpyrazin-2-yl)benzamide収率 43%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
120 °C

実験手順

To a solution of ethyl 2-[3-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(5-methylpyrazin-2-yl)carbamoyl]phenoxy]-4-methylsulfonyloxy-butanoate (Intermediate 27) (250 mg, 0.41 mmol) in acetonitrile (5 mL), was added sodium iodide (62 mg, 0.41 mmol) and cyclobutylamine (70 μL, 0.81 mmol). The resulting mixture was heated in a microwave at 120° C. for 60 minutes. The solvent was evaporated under reduced pressure and the residue purified by flash chromatography eluting with 0-40% methanol in DCM to afford the product (95 mg, 43%). 1H NMR δ (300 MHz, CDCl3) 1.69-1.78 (2H, m), 2.13-2.23 (5H, m), 2.30-2.40 (2H, m), 2.55-2.64 (4H, m), 3.39-3.47 (1H, m), 3.57-3.64 (1H, m), 4.24 (2H t), 4.62-4.72 (3H, m), 4.91-4.96 (1H, m), 6.96 (1H, t), 7.22 (1H t), 7.36-7.40 (1H, m), 7.45 (1H, t), 8.09-8.13 (2H, m), 8.32 (1H, d), 8.61 (1H, s), 9.51 (1H, d); m/z 543 (M+H)+.

後処理

  1. customThe solvent was evaporated under reduced pressure
  2. customthe residue purified by flash chromatography
  3. washeluting with 0-40% methanol in DCM

出典と根拠

ORDレコード
ord-1af5cc8cc7c148cc81e3e8743dffcf80
出典データセット
uspto-grants-2011_03
特許番号
US07902200B2

反応ノート

読み込み中…