Methanol → trans-2-Amino-6,6a,8,9,10,10a-hexahydropyrido[2,3-h]quinazoline-7(5H)-carboxylic acid, 1,1-dimethylethyl ester

HRID 34653

反応式

HRID 34653 の反応式
O=[C:2]1[CH2:11][CH2:10][CH2:9][C@@H:8]2[C@@H:3]1[CH2:4][CH2:5][CH2:6][N:7]2[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].[CH3:19][N:20]([CH:22]([N:26](C)C)[N:23](C)C)C.CO.C(=O)(O)O.NC(N)=N>C1(C)C=CC=CC=1>[NH2:26][C:22]1[N:20]=[CH:19][C:11]2[CH2:10][CH2:9][C@@H:8]3[N:7]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:6][CH2:5][CH2:4][C@H:3]3[C:2]=2[N:23]=1

参加物

6

反応物 4

HCID 887MethanolHCID 79831N,N,N',N',N'',N''-HexamethylmethanetriamineHCID 286947Carbonic acid-guanidine (1:1)HCID 13528263trans octahydro-5-oxo-1(2H)-quinolinecarboxylic acid, 1,1-dimethylethyl ester

生成物 1

HCID 14233850trans-2-Amino-6,6a,8,9,10,10a-hexahydropyrido[2,3-h]quinazoline-7(5H)-carboxylic acid, 1,1-dimethylethyl ester

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒2 回

実験手順

To a refluxing solution, under nitrogen, of 8.89 g (35 mmol) of cis and trans octahydro-5-oxo-1(2H)-quinolinecarboxylic acid, 1,1-dimethylethyl ester, (Example 8), in 400 ml of toluene is added dropwise a solution of 6.37 g (43.8 mmol) of tris-(dimethylamino)methane in 200 ml of toluene. The solution is refluxed for 2 hours. The reaction mixture is concentrated and the residue is dissolved in 500 ml of methanol. To the methanol solution is added 12.64 g (70.1 mmol) of guanidine carbonate, and the reaction mixture is refluxed, under nitrogen, for 12 hours. The mixture is concentrated and partitioned between brine and chloroform. The organic phase is separated, dried over magnesium sulfate, filtered and concentrated to a yellow solid. Medium pressure chromatography (silica gel, ethyl acetate) afforded 4.55 g (51%) of recovered starting ketone, 0.94 g (8.8%) of (±) cis-2-amino-6,6a,8,9,10,10a-hexahydropyrido[2,3-h]quinazoline-7(5H)-carboxylic acid, 1,1-dimethylethyl ester (Rf =0.33 (ethyl acetate)) as a foamy off-white solid, mp 178°-182° C., and 2.47 g (23%) of (±) trans-2-amino-6,6a,8,9,10,10a-hexahydropyrido[2,3-h]quinazoline-7(5H)-carboxylic acid, 1,1-dimethylethyl ester (Rf =0.27 (ethyl acetate)) as a white solid, mp 200°-206° C. (dec.).

後処理

  1. temperatureThe solution is refluxed for 2 hours
  2. concentrationThe reaction mixture is concentrated
  3. dissolutionthe residue is dissolved in 500 ml of methanol
  4. temperaturethe reaction mixture is refluxed, under nitrogen, for 12 hours
  5. concentrationThe mixture is concentrated
  6. custompartitioned between brine and chloroform
  7. customThe organic phase is separated
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated to a yellow solid
  11. customMedium pressure chromatography (silica gel, ethyl acetate) afforded 4.55 g (51%)
  12. customof recovered

出典と根拠

ORDレコード
ord-3e0a511035a24c2bb01c17e9545cb034
出典データセット
uspto-grants-1988_08
特許番号
US04762843

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