Triphenylphosphine → 4-chloro-3-(1-methyl-1H-pyrazol-4-yl)-1-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyl-1H-pyrazolo[3,4-c]pyridazine

HRID 2205764Notes

Reaction equation

HRID 2205764 reaction equation
[Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[N:6][N:5]=[C:4]2[NH:14][N:15]=[C:16](I)[C:3]=12.ClC1C(C2C=CC=CC=2)=NN=[C:21]2[NH:31][N:32]=[CH:33][C:20]=12.[CH3:34][N:35]1[CH2:40][CH2:39][N:38]([CH2:41][CH2:42]O)[CH2:37][CH2:36]1.N(C(OCC)=O)=N[C:46](OCC)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCOCC1>[Cl:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[N:6][N:5]=[C:4]2[N:14]([CH2:42][CH2:41][N:38]3[CH2:39][CH2:40][N:35]([CH3:34])[CH2:36][CH2:37]3)[N:15]=[C:16]([C:20]3[CH:21]=[N:31][N:32]([CH3:46])[CH:33]=3)[C:3]=12

Participants

7

Reactant 5

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 2311841-(2-Hydroxyethyl)-4-methylpiperazineHCID 867172634-chloro-5-phenyl-1H-pyrazolo[3,4-c]pyridazineHCID 86717264CID 86717264

Product 1

HCID 742209534-chloro-3-(1-methyl-1H-pyrazol-4-yl)-1-(2-(4-methylpiperazin-1-yl)ethyl)-5-phenyl-1H-pyrazolo[3,4-c]pyridazine

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of 4-chloro-3-iodo-5-phenyl-1H-pyrazolo[3,4-c]pyridazine and 4-chloro-5-phenyl-1H-pyrazolo[3,4-c]pyridazine (9:1, 1.4 g), 2-(4-methylpiperazin-1-yl)ethanol (1.13 g, 7.8 mmol), diethyl azodicarboxylate (1.37 g, 7.8 mmol) and triphenyl phosphine (2.07 g, 7.9 mmol) in 1,4-dioxane (26 mL) was heated to 85° C. for 1 h and then cooled to room temperature and concentrated in vacuo. The residue was partially purified by column chromatography (silica gel, starting with iso-hexanes/ethyl acetate 1:0 to 0:1 and finishing with ethyl acetate/4 M NH3 in MeOH 1:0 to 9:1). The residue was purified by preparative HPLC to provide Compounds Ia, Ib, and 20.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was partially purified by column chromatography (silica gel, starting with iso-hexanes/ethyl acetate 1:0 to 0:1 and finishing with ethyl acetate/4 M NH3 in MeOH 1:0 to 9:1)
  3. customThe residue was purified by preparative HPLC
  4. customto provide Compounds Ia, Ib, and 20

Sources & evidence

ORD record
ord-7cb29c92e13e4562b99720371b2837f7
Source dataset
uspto-grants-2016_06
Patent number
US09371332B2

Reaction notes

Loading…