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Triethylamine → 4-Amino-5-cyclobutyloxy-6,7-dimethoxy-2-[4-(4-morpholinecarbonyl)-1,4-diazepan-1-yl]quinazoline

HRID 1004015
ノート
印刷プレビュー

反応式

HRID 1004015 の反応式
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:19][CH3:20])=[C:9]([O:17][CH3:18])[C:10]=2[O:12][CH:13]2[CH2:16][CH2:15][CH2:14]2)[N:5]=[C:4](Cl)[N:3]=1.Cl.[N:23]1([C:29]([N:31]2[CH2:37][CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)=[O:30])[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1.C(N(CC)CC)C>C(O)CCC>[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:19][CH3:20])=[C:9]([O:17][CH3:18])[C:10]=2[O:12][CH:13]2[CH2:16][CH2:15][CH2:14]2)[N:5]=[C:4]([N:34]2[CH2:35][CH2:36][CH2:37][N:31]([C:29]([N:23]3[CH2:24][CH2:25][O:26][CH2:27][CH2:28]3)=[O:30])[CH2:32][CH2:33]2)[N:3]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 8471TriethylamineHCID 184706574-Amino-2-chloro-5-cyclobutyloxy-6,7-dimethoxyquinazolineHCID 227070621-(4-Morpholinecarbonyl)-1,4-diazepane hydrochloride

生成物 1

HCID 184706584-Amino-5-cyclobutyloxy-6,7-dimethoxy-2-[4-(4-morpholinecarbonyl)-1,4-diazepan-1-yl]quinazoline収率 386.7%

試薬・触媒・溶媒 1

HCID 2631-Butanol
溶媒

実験手順

4-Amino-2-chloro-5-cyclobutyloxy-6,7-dimethoxyquinazoline (184 mg, 0.00059 mol) was added to a solution of 1-(4-morpholinecarbonyl)-1,4-diazepane hydrochloride (163 mg, 0.00065 mol) and triethylamine (184 μl, 0.0013 mol) in n-butanol (6 ml) and the reaction stirred at reflux for 2 hours. On cooling, the reaction was concentrated under reduced pressure and the residue partitioned between ethyl acetate (20 ml) and water (20 ml). The aqueous layer was further extracted with ethyl acetate (2×20 ml), the combined organic extracts dried (MgSO4), filtered and evaporated under reduced pressure. The crude product was purified on silica gel eluting with a solvent gradient of methanol:dichloromethane (0:100 to 7:93 v/v) to give the title compound as a white foam (1110 mg, 38%). MS m/z=487 (MH)+. 1H-NMR (CDCl3): δ=1.53 (1H, m), 1.76 (1H, m), 2.04 (2H, m), 2.25 (2H, m), 2.38 (2H, m), 3.20 (4H, t), 3,36 (2H, t), 3.55 (2H, t), 3.66 (4H, t), 3.80 (3H, s), 3.85 (3H, m), 3.94 (6H, m), 4.86 (1H, m), 6.62 (1H, s). Found: C, 58.09; H, 6.96; N, 16.69; C24H34N6O5 0.15CH2Cl2, requires C, 58.09; H, 6.92; N, 16.83%

後処理

  1. temperatureat reflux for 2 hours
  2. temperatureOn cooling
  3. concentrationthe reaction was concentrated under reduced pressure
  4. customthe residue partitioned between ethyl acetate (20 ml) and water (20 ml)
  5. extractionThe aqueous layer was further extracted with ethyl acetate (2×20 ml)
  6. dry with materialthe combined organic extracts dried (MgSO4)
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customThe crude product was purified on silica gel eluting with a solvent gradient of methanol:dichloromethane (0:100 to 7:93 v/v)

出典と根拠

ORDレコード
ord-a47f8a7ec80e46fb8b4dc4c2fc7b8190
出典データセット
uspto-grants-2000_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US06048864

反応ノート

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