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Methoxyacetaldehyde → 6-Methoxy-7-(1-(2-methoxyethyl)piperidin-4-ylmethoxy)-4-(2-methylindol-5-yloxy)quinazoline

HRID 454071
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HRID 454071 반응식
[CH3:1][O:2][CH2:3][CH:4]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH3:20][O:21][C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][C:31]=1[O:32][CH2:33][CH:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1)[N:28]=[CH:27][N:26]=[C:25]2[O:40][C:41]1[CH:42]=[C:43]2[C:47](=[CH:48][CH:49]=1)[NH:46][C:45]([CH3:50])=[CH:44]2.C(=O)([O-])O.[Na+]>C(Cl)Cl.CO>[CH3:20][O:21][C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][C:31]=1[O:32][CH2:33][CH:34]1[CH2:39][CH2:38][N:37]([CH2:4][CH2:3][O:2][CH3:1])[CH2:36][CH2:35]1)[N:28]=[CH:27][N:26]=[C:25]2[O:40][C:41]1[CH:42]=[C:43]2[C:47](=[CH:48][CH:49]=1)[NH:46][C:45]([CH3:50])=[CH:44]2
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참가 물질

7

반응물 4

HCID 91563MethoxyacetaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 220308736-Methoxy-4-(2-methylindol-5-yloxy)-7-(piperidin-4-ylmethoxy)quinazoline

생성물 1

HCID 220306856-Methoxy-7-(1-(2-methoxyethyl)piperidin-4-ylmethoxy)-4-(2-methylindol-5-yloxy)quinazoline수율 47.3%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6344Dichloromethane용매

실험 절차

Methoxyacetaldehyde (368 mg, 3.47 mol) (freshly distilled) followed by sodium triacetoxyborohydride (552 mg, 2.6 mol) were added to a solution of 6-methoxy-4-(2-methylindol-5-yloxy)-7-(piperidin-4-ylmethoxy)quinazoline (726 mg, 1.74 mmol), (prepared as described in Example 70), in a mixture of methylene chloride (15 ml) and methanol (15 ml). After stirring for 1.5 hours at ambient temperature, saturated sodium hydrogen carbonate was added. The volatiles were removed under vacuum and the residue was partitioned between methylene chloride and water. The organic layer, was separated, washed with water, brine, dried (MgSO4) and the volatiles were removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (80/20). After removal of the solvent, the residue was triturated with ether, collected by filtration, washed with ether and dried under vacuum at 60° C. to give 6-methoxy-7-(1-(2-methoxyethyl)piperidin-4-ylmethoxy)-4-(2-methylindol-5-yloxy)quinazoline (392 mg, 47%).

후처리

  1. customThe volatiles were removed under vacuum
  2. customthe residue was partitioned between methylene chloride and water
  3. customThe organic layer, was separated
  4. washwashed with water, brine
  5. dry with materialdried (MgSO4)
  6. customthe volatiles were removed by evaporation
  7. customThe residue was purified by column chromatography
  8. washeluting with methylene chloride/methanol (80/20)
  9. customAfter removal of the solvent
  10. customthe residue was triturated with ether
  11. filtrationcollected by filtration
  12. washwashed with ether
  13. customdried under vacuum at 60° C.

출처 및 근거

ORD 기록
ord-90e9a818006e49b8a64bdc1c6fee52e9
출처 데이터셋
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08492560B2

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