Phosphorus oxychloride → 4-Chloro-1-[2-(4-methylpiperazin-1-yl)ethyl]-5-phenyl-3-pyrrolidin-1-yl-pyrazolo[3,4-c]pyridazine

HRID 2205784Notes

Reaction equation

[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]2[C:14]3[N:15]=[N:16][C:17]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)=[C:18](O)[C:13]=3[C:12]([N:26]3[CH2:30][CH2:29][CH2:28][CH2:27]3)=[N:11]2)[CH2:4][CH2:3]1.O=P(Cl)(Cl)[Cl:33]>C(Cl)Cl>[Cl:33][C:18]1[C:17]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[N:16][N:15]=[C:14]2[N:10]([CH2:9][CH2:8][N:5]3[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]3)[N:11]=[C:12]([N:26]3[CH2:30][CH2:29][CH2:28][CH2:27]3)[C:13]=12

Participants

Conditions

Temperature: 60 °C

Procedure

A suspension of 1-[2-(4-methylpiperazin-1-yl)ethyl]-5-phenyl-3-pyrrolidin-1-yl-pyrazolo[3,4-c]pyridazin-4-ol (90 mg) in POCl3 (6 mL) and CH2Cl2 (3 mL) was heated to 60° C. for 2.5 h. The mixture was concentrated in vacuo and the residue was partitioned between CH2Cl2 and sat. aq. NaHCO3 solution. The layers were separated and the aqueous was extracted with CH2Cl2, the combined organics were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by preparative HPLC to provide Compound Iz (12 mg).

Workup

concentrationThe mixture was concentrated in vacuo
customthe residue was partitioned between CH2Cl2 and sat. aq. NaHCO3 solution
customThe layers were separated
extractionthe aqueous was extracted with CH2Cl2
dry with materialthe combined organics were dried (MgSO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by preparative HPLC
customto provide Compound Iz (12 mg)

Sources & evidence

ORD record: ord-23759d6b4c2b40eaa8292e2a2d96e6c8
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09371332B2

Reaction notes

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