Diisopropylethylamine → Ethyl 2-(4-tert-butoxycarbonylpiperazin-1-yl)-5-methylamino-thiazole-4-carboxylate

HRID 1775354ノート

反応式

HRID 1775354 の反応式
Br[C:2]1[S:3][C:4]([NH:12][CH3:13])=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[N:6]=1.[N:14]1([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.CCN(C(C)C)C(C)C>O1CCOCC1>[C:23]([O:22][C:20]([N:14]1[CH2:19][CH2:18][N:17]([C:2]2[S:3][C:4]([NH:12][CH3:13])=[C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[N:6]=2)[CH2:16][CH2:15]1)=[O:21])([CH3:26])([CH3:24])[CH3:25]

参加物

5

反応物 3

HCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 53613688Ethyl 2-bromo-5-(methylamino)-1,3-thiazole-4-carboxylate

生成物 1

HCID 89825828Ethyl 2-(4-tert-butoxycarbonylpiperazin-1-yl)-5-methylamino-thiazole-4-carboxylate収率 35.2%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

To a solution of ethyl 2-bromo-5-methylamino-thiazole-4-carboxylate (401 mg, 1.512 mmol) and tert-butyl piperazine-1-carboxylate (1.06 g, 5.69 mmol) in anhydrous dioxane (15 ml) was added DIPEA (2 ml, 11.5 mmol) and the reaction was heated at 100° C. in a sealed flask for 23 hours. The mixture was cooled to room temperature, partitioned between DCM and sat. sodium bicarbonate solution and the phases were separated. The aqueous layer was extracted twice with DCM and the combined organic layers were dried (sodium sulfate) and concentrated under reduced pressure. The residue was purified by column chromatography (silica, gradient from 10 to 70% ethyl acetate in n-heptane) to yield 197 mg of a white solid (0.532 mmol, yield 35%) MS (multi-mode) m/z=371.2 [M+1]+.

後処理

  1. temperatureThe mixture was cooled to room temperature
  2. custompartitioned between DCM and sat. sodium bicarbonate solution
  3. customthe phases were separated
  4. extractionThe aqueous layer was extracted twice with DCM
  5. dry with materialthe combined organic layers were dried (sodium sulfate)
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography (silica, gradient from 10 to 70% ethyl acetate in n-heptane)

出典と根拠

ORDレコード
ord-17f9f95bb6a346e9a3b2526fc373f2b1
出典データセット
uspto-grants-2016_02
特許番号
US09260441B2

反応ノート

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