Pyrrolidine → HCID 178480892, 화합물

HRID 588581노트

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HRID 588581 반응식
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

참가 물질

8

반응물 3

HCID 31268Pyrrolidine2회HCID 23676156Sodium t-butoxideHCID 1784808913-Iodo-1-[2-(4-methylpiperazin-1-yl)ethyl]-5-phenyl-pyrazolo[3,4-c]pyridazin-4-ol

생성물 1

HCID 178480892HCID 178480892, 화합물수율 88.7%

시약·촉매·용매 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)촉매2회HCID 9811564Bis(dibenzylideneacetone)palladium촉매2회HCID 679Dimethyl Sulfoxide용매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-0e7e3b76be0e413480b7a1e0f23abd82
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09227976B2

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