Sodium hydride → (E)-methyl 3-(5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl)acrylate

HRID 2036816ノート

反応式

HRID 2036816 の反応式
[CH3:1][O:2][C:3]([CH2:5]P(OC)(OC)=O)=[O:4].[H-].[Na+].[C:14]1([C:20]2[CH:29]=[CH:28][CH:27]=[C:26]3[C:21]=2[C:22]([NH:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][N:35]=2)=[N:23][C:24]([CH:30]=O)=[N:25]3)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C1COCC1>[C:14]1([C:20]2[CH:29]=[CH:28][CH:27]=[C:26]3[C:21]=2[C:22]([NH:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][N:35]=2)=[N:23][C:24](/[CH:30]=[CH:5]/[C:3]([O:2][CH3:1])=[O:4])=[N:25]3)[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 80029Trimethyl phosphonoacetateHCID 866706195-Phenyl-4-(pyridin-2-ylmethylamino)quinazoline-2-carbaldehyde

生成物 1

HCID 67055877(E)-methyl 3-(5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl)acrylate収率 72%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

A solution of trimethyl phosphonoacetate (0.225 g 1.00 mmol) in THF (20 mL) was added 95% sodium hydride (0.050 g, 2.0 mmol). Upon the completion of addition, the mixture was stirred at 0° C. for 30 min and then 5-phenyl-4-(pyridin-2-ylmethylamino)quinazoline-2-carbaldehyde (Example 212, prepared in a similar manner to the procedure described below, 0.340 g, 1.00 mmol) was added to the reaction mixture. The resulting mixture was stirred at room temperature for 14 h. After this time, the reaction mixture was quenched with saturated aqueous ammonium chloride solution (50 mL) and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and filtrated. The filtrate was concentrated and the resulting residue was subjected to silica gel column chromatography using 5% MeOH in chloroform as the eluent to provide (E)-methyl 3-(5-phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl)acrylate (0.30 g, 72%) as a brown solid. LCMS Method V: retention time 1.94 min; [M+1]=411.2.

後処理

  1. additionUpon the completion of addition
  2. additionwas added to the reaction mixture
  3. stirringThe resulting mixture was stirred at room temperature for 14 h
  4. customAfter this time, the reaction mixture was quenched with saturated aqueous ammonium chloride solution (50 mL)
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltrated
  9. concentrationThe filtrate was concentrated

出典と根拠

ORDレコード
ord-90df72b2906e43998fd75a594eca65b0
出典データセット
uspto-grants-2013_11
特許番号
US08575184B2

反応ノート

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