Pyridine → 2-[2-(tert-Butyl-dimethyl-silanyloxy)-ethylamino]-6-chloro-nicotinonitrile

HRID 1483752ノート

反応式

HRID 1483752 の反応式
[C:1]([Si:5]([CH3:21])([CH3:20])[O:6][CH2:7][CH2:8][NH:9][C:10]1[N:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:11]=1[C:12]([NH2:14])=O)([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1.O=P(Cl)(Cl)Cl.[OH-].[Na+]>C(#N)C.CCOC(C)=O>[C:1]([Si:5]([CH3:21])([CH3:20])[O:6][CH2:7][CH2:8][NH:9][C:10]1[N:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:11]=1[C:12]#[N:14])([CH3:4])([CH3:3])[CH3:2]

参加物

7

反応物 4

HCID 1049PyridineHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 579687112-[2-(tert-Butyl-dimethyl-silanyloxy)-ethylamino]-6-chloro-nicotinamide

生成物 1

HCID 866364682-[2-(tert-Butyl-dimethyl-silanyloxy)-ethylamino]-6-chloro-nicotinonitrile収率 78%

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
60 °C

実験手順

To a solution of 2-[2-(tert-butyl-dimethyl-silanyloxy)-ethylamino]-6-chloro-nicotinamide (3, 300 mg, 0.96 mmol) in acetonitrile (anhydrous, 50 mL) were added pyridine (0.62 mL, 7.65 mmol) and POCl3 (0.35 mL, 382 mmol). The reaction was heated at 60° C. for 1 hour. After cooling to room temperature, NaOH solution (10% aq.) was slowly added till pH 9. EtOAc (200 mL) was added and the layers separated. The aqueous layer was extracted with EtOAc (2×200 mL). The combined organic layer was dried over MgSO4, filtered, and concentrated in vacuo. Purification was accomplished by silica gel chromatography, eluting with 1%-20% EtOAc/hexanes gradient, to afford 220 mg (78% yield) of the titled product.

後処理

  1. temperatureAfter cooling to room temperature
  2. customthe layers separated
  3. extractionThe aqueous layer was extracted with EtOAc (2×200 mL)
  4. dry with materialThe combined organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification
  8. washeluting with 1%-20% EtOAc/hexanes gradient

出典と根拠

ORDレコード
ord-3e37a75ea94846bca02f184eedd8d972
出典データセット
uspto-grants-2016_08
特許番号
US09416146B2

反応ノート

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