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6-(Bromomethyl)-4-chloroquinazoline → HCID 86757280, 화합물

HRID 651632
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HRID 651632 반응식
[CH3:1][N:2]([C@H:18]1[CH2:22][CH2:21][NH:20][C:19]1=[O:23])[S:3]([C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][C:10]([O:16][CH3:17])=[CH:11][CH:12]=2)[CH:7]=1)(=[O:5])=[O:4].[Li]N([Si](C)(C)C)[Si](C)(C)C.Br[CH2:35][C:36]1[CH:37]=[C:38]2[C:43](=[CH:44][CH:45]=1)[N:42]=[CH:41][N:40]=[C:39]2[Cl:46]>C1COCC1>[Cl:46][C:39]1[C:38]2[C:43](=[CH:44][CH:45]=[C:36]([CH2:35][N:20]3[CH2:21][CH2:22][C@H:18]([N:2]([CH3:1])[S:3]([C:6]4[CH:15]=[CH:14][C:13]5[C:8](=[CH:9][C:10]([O:16][CH3:17])=[CH:11][CH:12]=5)[CH:7]=4)(=[O:5])=[O:4])[C:19]3=[O:23])[CH:37]=2)[N:42]=[CH:41][N:40]=1
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참가 물질

5

반응물 3

HCID 219419376-(Bromomethyl)-4-chloroquinazolineHCID 54147218HCID 54147218, 화합물HCID 178418261HCID 178418261, 화합물

생성물 1

HCID 86757280HCID 86757280, 화합물수율 52.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

To a solution of 7-methoxynaphthalene-2-sulfonic acid methyl-(2-oxopyrrolidin-3-(S)-yl)-amide (0.35 g, 1.04 mmol) in THF (7 mL) at 0° C. is added LiN(SiMe3)2 (1 mL, 1 mmol, 1 M solution in THF). The solution is stirred at 0° C. for 40 minutes. After this time, 6-bromomethyl-4-chloro-quinazoline (0.24 g, 0.94 mmol) is added. The resulting solution is stirred for 4 hours. The reaction is quenched by the addition of a saturated NH4Cl solution. The solution is diluted with EtOAc and water. The layers are separated. The organic layer is washed with water and brine. The organic layer is dried over MgSO4, filtered and concentrated. The crude product is purified by column chromatography eluting with a gradient of 20% EtOAc/CH2Cl2 to 40% EtOAc/CH2Cl2 to give the title compound (0.25 g, 0.49 mmol) as a white solid.

후처리

  1. stirringThe resulting solution is stirred for 4 hours
  2. customThe reaction is quenched by the addition of a saturated NH4Cl solution
  3. additionThe solution is diluted with EtOAc and water
  4. customThe layers are separated
  5. washThe organic layer is washed with water and brine
  6. dry with materialThe organic layer is dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product is purified by column chromatography
  10. washeluting with a gradient of 20% EtOAc/CH2Cl2 to 40% EtOAc/CH2Cl2

출처 및 근거

ORD 기록
ord-3acea98b22f4471a92a260e8f994e6c5
출처 데이터셋
uspto-grants-2001_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06281227B1

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