Propanal → 3H-1,5-Benzodiazepine, 2,4-bis(4-methyl-1-piperazinyl)-3-propylidene-

HRID 1782397ノート

反応式

HRID 1782397 の反応式
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH2:9][C:10]([N:19]3[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)=[N:11][C:12]3[CH:18]=[CH:17][CH:16]=[CH:15][C:13]=3[N:14]=2)[CH2:4][CH2:3]1.[CH:26]([N-]C(C)C)([CH3:28])[CH3:27].[Li+].C(=O)CC.C(N(CC)CC)C.N1C=CC=CC=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O.[OH-].[Na+]>O1CCCC1.CO>[CH3:1][N:2]1[CH2:3][CH2:4][N:5]([C:8]2[C:9](=[CH:27][CH2:26][CH3:28])[C:10]([N:19]3[CH2:20][CH2:21][N:22]([CH3:25])[CH2:23][CH2:24]3)=[N:11][C:12]3[CH:18]=[CH:17][CH:16]=[CH:15][C:13]=3[N:14]=2)[CH2:6][CH2:7]1

参加物

10

反応物 7

HCID 527PropanalHCID 1049PyridineHCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 14798Sodium HydroxideHCID 2724682Lithium diisopropylamideHCID 117248372,4-Bis(4-methyl-1-piperazinyl)-3H-1,5-benzodiazepine

生成物 1

HCID 102492283H-1,5-Benzodiazepine, 2,4-bis(4-methyl-1-piperazinyl)-3-propylidene-収率 36,843.398%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-30 °C

実験手順

A suspension of 2,4-bis(4-methyl-1-piperazinyl)-3H-[1,5]benzodiazepine (1.702 g, 5 mmol) in tetrahydrofuran (20 ml) under constant flow of argon was cooled to −30° C. A solution of lithium diisopropylamide (LDA) (2 M, 3.75 ml, 7.5 mmol) was added dropwise. Thus obtained dark brown suspension was allowed to warm to −5° C. until dissolved and then again cooled to −30° C. Propionaldehyd (0.54 ml, 7.5 mmol) was added during 5 min. The resulting clear yellow solution was allowed to warm to −5° C., triethylamine (5.55 ml, 40 mmol) and pyridine (0.040 ml, 0.5 mmol) were added. A solution of trifluoroacetic anhydride (4.2 ml, 30 mmol) in tetrahydrofuran (6 ml) was added dropwise maintaining the temperature at −5° C. The reaction mixture was stirred for another hour. Methanol (5 ml) and while strongly agitated NaOH (1 M, 35 ml) were added dropwise. The reaction mixture was stirred for four hours while slowly warming to room temperature. The solution was made acidic at ph of 1 and extracted with dichloromethane (3×25 ml). The water phase was made alkalic at a pH of 10 and extracted with diethyl ether (15×25 ml). After each extraction water phase was adjusted to pH of 10. The ether phase was dried over anhydrous Na2SO4 and ether was evaporated at reduced pressure to give 1, 701 g (89%) of the title compound as a yellow resin.

後処理

  1. temperatureto warm to −5° C.
  2. dissolutionuntil dissolved
  3. temperatureagain cooled to −30° C
  4. temperatureto warm to −5° C.
  5. temperaturemaintaining the temperature at −5° C
  6. stirringThe reaction mixture was stirred for four hours
  7. temperaturewhile slowly warming to room temperature
  8. extractionextracted with dichloromethane (3×25 ml)
  9. extractionextracted with diethyl ether (15×25 ml)
  10. extractionAfter each extraction water phase
  11. dry with materialThe ether phase was dried over anhydrous Na2SO4 and ether
  12. customwas evaporated at reduced pressure

出典と根拠

ORDレコード
ord-b122cf529c28402ba6b23f656be4f042
出典データセット
uspto-grants-2009_03
特許番号
US07498433B2

反応ノート

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