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

HRID 2036816노트

반응식

HRID 2036816 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
0 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-90df72b2906e43998fd75a594eca65b0
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08575184B2

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