Pyrrolidine → HCID 178480892、化合物

HRID 588581ノート

反応式

HRID 588581 の反応式
I[C:2]1[C:10]2[C:9]([OH:11])=[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[N:7]=[N:6][C:5]=2[N:4]([CH2:18][CH2:19][N:20]2[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]2)[N:3]=1.[NH:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1.CC(C)([O-])C.[Na+]>O1CCOCC1.CS(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[CH3:26][N:23]1[CH2:24][CH2:25][N:20]([CH2:19][CH2:18][N:4]2[C:5]3[N:6]=[N:7][C:8]([C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=4)=[C:9]([OH:11])[C:10]=3[C:2]([N:27]3[CH2:31][CH2:30][CH2:29][CH2:28]3)=[N:3]2)[CH2:21][CH2:22]1

参加物

8

反応物 3

HCID 31268Pyrrolidine2 回HCID 23676156Sodium t-butoxideHCID 1784808913-Iodo-1-[2-(4-methylpiperazin-1-yl)ethyl]-5-phenyl-pyrazolo[3,4-c]pyridazin-4-ol

生成物 1

HCID 178480892HCID 178480892、化合物収率 88.7%

試薬・触媒・溶媒 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)触媒2 回HCID 9811564Bis(dibenzylideneacetone)palladium触媒2 回HCID 679Dimethyl Sulfoxide溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

To a solution of 3-iodo-1-[2-(4-methylpiperazin-1-yl)ethyl]-5-phenyl-pyrazolo[3,4-c]pyridazin-4-ol (120 mg, 0.26 mmol) in dioxane (1.7 mL) and DMSO (0.9 mL) was added pyrrolidine (233 μL, 2.8 mmol) and sodium t-butoxide (37 mg, 0.39 mmol) and nitrogen was bubbled in the resulting mixture for 30 min. Pd2 dba3 (24 mg, 0.026 mmol) and Xantphos (9 mg, 0.016 mmol) were then added, the tube flushed with nitrogen, sealed and heated to 100° C. for 5 h. Pyrrolidine (40 μL, 0.49 mmol), Pd2 dba3 (24 mg, 0.026 mmol) and Xantphos (9 mg, 0.016 mmol) were added and the mixture was heated to 100° C. for another 1 h. The mixture was left to cool to rt, then neutralised to pH 2-3 before loading on an SCX (10 g) cartridge. The cartridge was eluted with MeOH then CH2Cl2/MeOH (1:1) and finally the product was released with 10% methanolic ammonia (7 N) in CH2Cl2/MeOH (1:1). Evaporation of the solvent gave the title compound as a yellow glass (94 mg) which was reacted as such in the next step.

後処理

  1. customwas bubbled in the resulting mixture for 30 min
  2. customthe tube flushed with nitrogen
  3. customsealed
  4. temperaturethe mixture was heated to 100° C. for another 1 h
  5. waitThe mixture was left
  6. temperatureto cool to rt
  7. washThe cartridge was eluted with MeOH
  8. customEvaporation of the solvent

出典と根拠

ORDレコード
ord-0e7e3b76be0e413480b7a1e0f23abd82
出典データセット
uspto-grants-2016_01
特許番号
US09227976B2

反応ノート

読み込み中…