Sodium hydride → 7(N-tert-butoxycarbonylpiperidin-4-ylmethoxy)-4-(5-chloro-2,3-methylenedioxypyrid-4-ylamino)-6-methoxyquinazoline

HRID 2374439

반응식

HRID 2374439 반응식
[NH2:1][C:2]1[C:7]([Cl:8])=[CH:6][N:5]=[C:4]2[O:9][CH2:10][O:11][C:3]=12.[H-].[Na+].[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][CH:24]([CH2:27][O:28][C:29]2[CH:38]=[C:37]3[C:32]([C:33](Cl)=[N:34][CH:35]=[N:36]3)=[CH:31][C:30]=2[O:40][CH3:41])[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15]>CN(C=O)C>[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][CH:24]([CH2:27][O:28][C:29]2[CH:38]=[C:37]3[C:32]([C:33]([NH:1][C:2]4[C:7]([Cl:8])=[CH:6][N:5]=[C:4]5[O:9][CH2:10][O:11][C:3]=45)=[N:34][CH:35]=[N:36]3)=[CH:31][C:30]=2[O:40][CH3:41])[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15]

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 219360467-(N-tert-butoxycarbonylpiperidin-4-ylmethoxy)-4-chloro-6-methoxyquinazolineHCID 685486516-chloro-2H-[1,3]dioxolo[4,5-b]pyridin-7-amine

생성물 1

HCID 685487457(N-tert-butoxycarbonylpiperidin-4-ylmethoxy)-4-(5-chloro-2,3-methylenedioxypyrid-4-ylamino)-6-methoxyquinazoline

시약·촉매·용매 1

HCID 6228Dimethylformamide용매3회

실험 절차

Using a similar procedure to that described in Example 1, a solution of 4-amino-5-chloro-2,3-methylenedioxypyridine (0.193 g) in DMF (2 ml) was added to a stirred suspension of sodium hydride (60% dispersion in mineral oil, 0.048 g) in DMF (2 ml) and the mixture was stirred at ambient temperature for 15 minutes. A solution of 7-(N-tert-butoxycarbonylpiperidin-4-ylmethoxy)-4-chloro-6-methoxyquinazoline [International Patent Application WO 02/16352 (Note [24] within Example 2 thereof; 0.38 g] in DMF (4 ml) was added and the resultant mixture was stirred at ambient temperature for 1 hour. The reaction mixture was partitioned between ethyl acetate and brine. The organic phase was dried over magnesium sulphate and evaporated. The residue was purified by column chromatography on silica using a 49:1 mixture of methylene chloride and methanol. There was thus obtained the title compound as a solid (0.24 g); NMR Spectrum: DMSOd6) 1.29 (m, 2H), 1.45 (s, 9H), 1.8 (m, 2H), 2.04 (m, 1H), 2.83 (m, 2H), 4.0 (m, 7H), 8.12 (br s, 2H), 7.17 (br s, 1H), 7.72 (m, 2H), 8.37 (br s, 1H), 9.37 (br s, 1H); Mass Spectrum: M+H+ 544 and 546.

후처리

  1. customThe reaction mixture was partitioned between ethyl acetate and brine
  2. dry with materialThe organic phase was dried over magnesium sulphate
  3. customevaporated
  4. customThe residue was purified by column chromatography on silica using
  5. additiona 49:1 mixture of methylene chloride and methanol

출처 및 근거

ORD 기록
ord-d4b92020e037417db9b6e668c58cc513
출처 데이터셋
uspto-grants-2008_12
특허 번호
US07462623B2

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