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Diethyl Ether → 4-Amino-6-benzyloxy-7-methoxy-2-[4-(4-morpholinecarbonyl)-1,4-diazepan-1-yl]quinazoline

HRID 1004002
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HRID 1004002 반응식
Cl.[N:2]1([C:8]([N:10]2[CH2:16][CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[O:9])[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1.[NH2:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:36][CH3:37])=[C:25]([O:28][CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH:26]=2)[N:21]=[C:20](Cl)[N:19]=1.C(N(CC)CC)C.C(OCC)C>C(O)CCC>[NH2:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:36][CH3:37])=[C:25]([O:28][CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH:26]=2)[N:21]=[C:20]([N:13]2[CH2:14][CH2:15][CH2:16][N:10]([C:8]([N:2]3[CH2:3][CH2:4][O:5][CH2:6][CH2:7]3)=[O:9])[CH2:11][CH2:12]2)[N:19]=1
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참가 물질

6

반응물 4

HCID 3283Diethyl EtherHCID 8471TriethylamineHCID 109799944-Amino-6-benzyloxy-2-chloro-7-methoxyquinazolineHCID 227070621-(4-Morpholinecarbonyl)-1,4-diazepane hydrochloride

생성물 1

HCID 109620274-Amino-6-benzyloxy-7-methoxy-2-[4-(4-morpholinecarbonyl)-1,4-diazepan-1-yl]quinazoline수율 70%

시약·촉매·용매 1

HCID 263
1-Butanol
용매

실험 절차

1-(4-Morpholinecarbonyl)-1,4-diazepane hydrochloride (16 g, 0.075 mol) and 4-amino-6-benzyloxy-2-chloro-7-methoxyquinazoline (15 g, 0.048 mol) were added to a solution of triethylamine (20 ml, 0.144 mol) in n-butanol (200 ml) and the reaction stirred at reflux for 1 hour. On cooling, the mixture was concentrated under reduced pressure and the residue partitioned between dichloromethane (400 ml) and water (400 ml). The phases were separated and the organic layer dried (MgSO4), filtered and evaporated under reduced pressure to give a cream coloured solid. Trituration with diethyl ether gave the title compound as a solid (16.35 g, 70%). Rf 0.50 (0.880 aqueous ammonia:methanol:dichloromethane 1:7:92, v/v). MS m/z 493 (MH)+. 1H-NMR (CDCl3): δ=2.03 (2H, m), 3.18 (4H, m), 3.34 (2H, t), 3.56 (2H, m), 3.65 (5H, m), 3.85 (2H, m), 4.00 (4H, m), 5.00 (1H, bs), 5.18 (2H, s), 6.87 (1H, bs), 7.37 (4H, m), 7.47 (3H, m).

후처리

  1. temperatureat reflux for 1 hour
  2. temperatureOn cooling
  3. concentrationthe mixture was concentrated under reduced pressure
  4. customthe residue partitioned between dichloromethane (400 ml) and water (400 ml)
  5. customThe phases were separated
  6. dry with materialthe organic layer dried (MgSO4)
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customto give a cream

출처 및 근거

ORD 기록
ord-cc7be598e08b45c38a61dc494a64e083
출처 데이터셋
uspto-grants-2000_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06048864

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