Pyrrolidine → HCID 178480892, compound

HRID 588581Notes

Reaction equation

HRID 588581 reaction equation
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

Participants

8

Reactant 3

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

Product 1

HCID 178480892HCID 178480892, compoundYield 88.7%

Reagents, catalysts & solvents 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)Catalyst2×HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 679Dimethyl SulfoxideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-0e7e3b76be0e413480b7a1e0f23abd82
Source dataset
uspto-grants-2016_01
Patent number
US09227976B2

Reaction notes

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