Citric Acid → 4-Amino-5-cyclobutyloxy-6,7-dimethoxy-2-[4-(4-morpholinecarbonyl)-1,4-diazepan-1-yl]quinoline

HRID 1004023ノート

反応式

HRID 1004023 の反応式
C([N-:4]C(C)C)(C)C.[Li+].[CH:9]1([O:13][C:14]2[C:21]([O:22][CH3:23])=[C:20]([O:24][CH3:25])[CH:19]=[C:18]([N:26]=[C:27]([N:29]3[CH2:35][CH2:34][CH2:33][N:32]([C:36]([N:38]4[CH2:43][CH2:42][O:41][CH2:40][CH2:39]4)=[O:37])[CH2:31][CH2:30]3)[CH3:28])[C:15]=2[C:16]#[N:17])[CH2:12][CH2:11][CH2:10]1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1>[NH3:4].[NH2:17][C:16]1[C:15]2[C:18](=[CH:19][C:20]([O:24][CH3:25])=[C:21]([O:22][CH3:23])[C:14]=2[O:13][CH:9]2[CH2:10][CH2:11][CH2:12]2)[N:26]=[C:27]([N:29]2[CH2:35][CH2:34][CH2:33][N:32]([C:36]([N:38]3[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)=[O:37])[CH2:31][CH2:30]2)[CH:28]=1

参加物

6

反応物 3

HCID 311Citric AcidHCID 2724682Lithium diisopropylamideHCID 177736302-Cyclobutyloxy-3,4-dimethoxy-6-{1-[4-(morpholinecarbonyl)-1,4-diazepan-1-yl]ethylideneamino}benzonitrile

生成物 2

HCID 222AmmoniaHCID 187941994-Amino-5-cyclobutyloxy-6,7-dimethoxy-2-[4-(4-morpholinecarbonyl)-1,4-diazepan-1-yl]quinoline収率 67%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

A solution of lithium diisopropylamide in tetrahydrofuran (10 ml, 0.5M, 0.005 mol) was added to a solution of 2-cyclobutyloxy-3,4-dimethoxy-6-{1-[4-(morpholinecarbonyl)-1,4-diazepan-1-yl]ethylideneamino}benzonitrile (950 mg, 0.002 mol) in tetrahydrofuran (25 ml) at -70° C. and the reaction allowed to warm to room temperature under a nitrogen atmosphere. 1N aqueous citric acid solution (25 ml) was then added and the mixture extracted once with ethyl acetate (25 ml). The aqueous phase was basified using 1N aqueous sodium hydroxide solution and the mixture extracted with further ethyl acetate (60 ml) and these combined organic extracts dried (MgSO4), filtered and evaporated under reduced pressure. The crude product was purified on silica gel eluting with dichloromethane:methanol:0.880 aqueous ammonia (97:3:1 v/v) and trituration with diethyl ether gave the title compound as a foam (680 mg, 67%). Rf 0.31 (dichloromethane:methanol:0.880 aqueous ammonia, 97:3:1, v/v). MS m/z 486 (MH)+. 1H-NMR (CDCl3): δ=1.45 (1H, m), 1.70 (1H, m), 2.03 (2H, m), 2.30 (4H, m), 3.30 (4H, m), 3.35 (2H, m), 3.60 (8H, m), 3.80 (3H, s), 3.92 (5H, br.s), 4.80 (1H, m), 5.60 (2H, m), 570 (1H, s), 6.73 (1H, s). Found: C, 61.27; H, 7.39; N, 13.92; C25H35N5O5 1(C2H5)2O 0.3 H2O requires C, 61.21; H, 7.40; N, 14.05%.

後処理

  1. extractionthe mixture extracted once with ethyl acetate (25 ml)
  2. extractionthe mixture extracted with further ethyl acetate (60 ml)
  3. dry with materialthese combined organic extracts dried (MgSO4)
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customThe crude product was purified on silica gel eluting with dichloromethane

出典と根拠

ORDレコード
ord-552995bfbe36458f9dc307dc67aacea5
出典データセット
uspto-grants-2000_04
特許番号
US06048864

反応ノート

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