Sodium hydride → 4-(7-Methoxy-thiazolo[5,4-d]pyrimidin-2-ylcarbamoyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 550809ノート

反応式

HRID 550809 の反応式
[CH3:1][O:2][C:3]1[C:4]2[N:11]=[C:10]([NH2:12])[S:9][C:5]=2[N:6]=[CH:7][N:8]=1.[H-].[Na+].C(N(CC)C(C)C)(C)C.[C:24]([O:28][C:29]([N:31]1[CH2:36][CH2:35][N:34]([C:37](Cl)=[O:38])[CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25]>O1CCCC1>[C:24]([O:28][C:29]([N:31]1[CH2:32][CH2:33][N:34]([C:37](=[O:38])[NH:12][C:10]2[S:9][C:5]3[N:6]=[CH:7][N:8]=[C:3]([O:2][CH3:1])[C:4]=3[N:11]=2)[CH2:35][CH2:36]1)=[O:30])([CH3:27])([CH3:25])[CH3:26]

参加物

6

反応物 4

HCID 24758Sodium hydrideHCID 81531DiisopropylethylamineHCID 11334154Tert-butyl 4-(chlorocarbonyl)piperazine-1-carboxylateHCID 574765977-Methoxy-[1,3]thiazolo[5,4-d]pyrimidin-2-amine

生成物 1

HCID 590119304-(7-Methoxy-thiazolo[5,4-d]pyrimidin-2-ylcarbamoyl)-piperazine-1-carboxylic acid tert-butyl ester収率 74.5%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
50 °C

実験手順

A solution of 7-methoxy-thiazolo[5,4-d]pyrimidin-2-ylamine (3.5 g, 19.2 mmol) in tetrahydrofuran (100 mL) was treated with sodium hydride (60% in mineral oil, 2.3 g, 57 mmol) at 25° C. A slight evolution of gas was observed. The resulting purple slurry was warmed to 50° C. for 1 h. At this time, the reaction was cooled to 25° C. and was treated with N,N-diisopropylethylamine (10 mL, 57 mmol). The resulting mixture was stirred at 25° C. for 30 min. The mixture was then treated with a solution of 4-chlorocarbonyl-piperazine-1-carboxylic acid tert-butyl ester (4.73 g, 19 mmol) in tetrahydrofuran (20 mL) over a 10 min period. The reaction was stirred at 50° C. overnight. At this time, the reaction was concentrated in vacuo, diluted with methanol (100 mL) and absorbed onto silica gel (6 g). The silica gel was divided into two equal lots. ISCO chromatography (330 g, Silica, gradient elution 5/95 methanol/methylene chloride) afforded 4-(7-methoxy-thiazolo[5,4-d]pyrimidin-2-ylcarbamoyl)-piperazine-1-carboxylic acid tert-butyl ester (5.58 g, 74%) as an off-white solid; LRMS for C16H22N6O4S (M+H)+ at m/z=395. The NMR spectrum obtained on the sample is compatible with its structure.

後処理

  1. temperatureAt this time, the reaction was cooled to 25° C.
  2. stirringThe reaction was stirred at 50° C. overnight
  3. concentrationAt this time, the reaction was concentrated in vacuo
  4. additiondiluted with methanol (100 mL)
  5. customabsorbed onto silica gel (6 g)
  6. washISCO chromatography (330 g, Silica, gradient elution 5/95 methanol/methylene chloride)

出典と根拠

ORDレコード
ord-2ca2cb42ee384d328e68a8ad24956132
出典データセット
uspto-grants-2011_05
特許番号
US07947692B2

反応ノート

読み込み中…