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

반응식

HRID 34653 반응식
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

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 1140Toluene용매2회

실험 절차

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.).

후처리

  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

출처 및 근거

ORD 기록
ord-3e0a511035a24c2bb01c17e9545cb034
출처 데이터셋
uspto-grants-1988_08
특허 번호
US04762843

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