Sodium Bicarbonate → 5-{[2-(Pyrrolidin-1-yl)ethyl]sulfanyl}-1,3-thiazol-2-amine

HRID 559488ノート

反応式

HRID 559488 の反応式
C(=O)(O)[O-].[Na+].Br.Br[C:8]1[S:12][C:11]([NH2:13])=[N:10][CH:9]=1.[N:14]1([CH2:19][CH2:20][SH:21])[CH2:18][CH2:17][CH2:16][CH2:15]1>C(O)(C)C>[N:14]1([CH2:19][CH2:20][S:21][C:8]2[S:12][C:11]([NH2:13])=[N:10][CH:9]=2)[CH2:18][CH2:17][CH2:16][CH2:15]1

参加物

5

反応物 3

HCID 516892Sodium BicarbonateHCID 27238485-Bromothiazol-2-amine monohydrobromideHCID 211826982-(Pyrrolidin-1-yl)ethane-1-thiol

生成物 1

HCID 287826785-{[2-(Pyrrolidin-1-yl)ethyl]sulfanyl}-1,3-thiazol-2-amine収率 30.5%

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

反応条件

温度
60 °C

実験手順

Sodium bicarbonate ((1.232 kg, 14.7 mol) is added slowly in portions to a mixture of 5-bromo-thiazol-2-ylamine hydrobromide (1.53 Kg, 5.87 mol) in 7.5 L of isopropanol. 2-Pyrrolidin-1-yl-ethanethiol (1.060 Kg, 8.07 mol) is then added over 15 min, and the resulting mixture is stirred at 60° C. for 96 h. The temperature is increased to 70° C. for 1 h, and then the mixture is cooled to room temperature. Most of the isopropanol is removed under vacuum, and the residue is taken up in 4 L of an isopropanol/chloroform solution (1:9). Saturated aqueous sodium bicarbonate (4 L) is added, and the resulting mixture is stirred for 30 minutes. The layers are separated and the aqueous phase is extracted with three 4 L portions of an isopropanol/chloroform solution (1:9). The organic layers are combined, dried over sodium sulfate, filtered, and concentrated under vacuum. The resulting residue is triturated with 3 L of diethylether, and filtered off to give a first portion of the title compound as a pale-yellow solid (410 g). The filtrate is concentrated to an orange solid, which is triturated with 2 L of diethylether, and isolated as a beige solid by filtration. This solid is then dissolved in 2 L of methanol, and the solution is heated at 45° C. for 30 min. Upon cooling to room temperature, a solid is formed. This material is isolated by filtration, triturated with diethyl ether as above, and dried under vacuum to afford an additional 310 g of the title compound. MS (m/e): 230 [M+H]

後処理

  1. temperatureThe temperature is increased to 70° C. for 1 h
  2. temperaturethe mixture is cooled to room temperature
  3. customMost of the isopropanol is removed under vacuum
  4. additionSaturated aqueous sodium bicarbonate (4 L) is added
  5. stirringthe resulting mixture is stirred for 30 minutes
  6. customThe layers are separated
  7. extractionthe aqueous phase is extracted with three 4 L portions of an isopropanol/chloroform solution (1:9)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under vacuum
  11. customThe resulting residue is triturated with 3 L of diethylether
  12. filtrationfiltered off

出典と根拠

ORDレコード
ord-d4a9f5a217c742aa9061e4d00b184a3f
出典データセット
uspto-grants-2011_11
特許番号
US08063079B2

反応ノート

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