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Potassium Iodide → 7-((1-Cyanomethyl)piperidin-4-ylmethoxy)-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline

HRID 454122
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반응식

HRID 454122 반응식
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)[N:9]=[CH:8][N:7]=[C:6]2[O:21][C:22]1[CH:23]=[C:24]2[C:28](=[CH:29][CH:30]=1)[NH:27][C:26]([CH3:31])=[CH:25]2.Cl[CH2:33][C:34]#[N:35].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CN(C=O)C.O>[C:34]([CH2:33][CH:14]([CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)[O:13][C:12]1[CH:11]=[C:10]2[C:5]([C:6]([O:21][C:22]3[CH:23]=[C:24]4[C:28](=[CH:29][CH:30]=3)[NH:27][C:26]([CH3:31])=[CH:25]4)=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:2][CH3:1])#[N:35]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 4

HCID 4875Potassium IodideHCID 7856ChloroacetonitrileHCID 11430Potassium CarbonateHCID 220308736-Methoxy-4-(2-methylindol-5-yloxy)-7-(piperidin-4-ylmethoxy)quinazoline

생성물 1

HCID 220307667-((1-Cyanomethyl)piperidin-4-ylmethoxy)-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline수율 66.4%

시약·촉매·용매 2

HCID 962
Water
용매
HCID 6228Dimethylformamide용매

실험 절차

A mixture of 6-methoxy-4-(2-methylindol-5-yloxy)-7-(piperidin-4-ylmethoxy)quinazoline (419 mg, 1 mmol), (prepared as described in Example 70), in DMF (6 ml) containing chloroacetonitrile (114 mg, 1.5 mmol), potassium carbonate (346 mg, 2.5 mmol) and potassium iodide (50 mg, 0.3 mmol) was stirred at ambient temperature overnight. The mixture was poured into water and the precipitate was filtered, washed with water and dried under vacuum. The residue was purified by column chromatography, eluting with methylene chloride, followed by methylene chloride/methanol (98/2 and 95/5). After removal of the solvent under vacuum, the residue was triturated with ether, filtered, washed with ether and dried under vacuum to give 7-((1-cyanomethyl)piperidin-4-ylmethoxy)-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (304 mg, 66%).

후처리

  1. filtrationthe precipitate was filtered
  2. washwashed with water
  3. customdried under vacuum
  4. customThe residue was purified by column chromatography
  5. washeluting with methylene chloride
  6. customAfter removal of the solvent under vacuum
  7. customthe residue was triturated with ether
  8. filtrationfiltered
  9. washwashed with ether
  10. customdried under vacuum

출처 및 근거

ORD 기록
ord-d4374b64aa574b459aab1db692fd7229
출처 데이터셋
uspto-grants-2013_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08492560B2

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