Phosphorus oxychloride → 4-Chloro-1-methyl-5-phenyl-3-pyrrolidin-1-yl-pyrazolo[3,4-c]pyridazine

HRID 588644Notes

Reaction equation

HRID 588644 reaction equation
[CH3:1][N:2]1[C:6]2[N:7]=[N:8][C:9]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[C:10](O)[C:5]=2[C:4]([N:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)=[N:3]1.O=P(Cl)(Cl)[Cl:25]>>[Cl:25][C:10]1[C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[N:8][N:7]=[C:6]2[N:2]([CH3:1])[N:3]=[C:4]([N:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)[C:5]=12

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 1784819221-methyl-5-phenyl-3-(pyrrolidin-1-yl)-1H-pyrazolo[3,4-c]pyridazin-4-ol

Product 1

HCID 867173374-Chloro-1-methyl-5-phenyl-3-pyrrolidin-1-yl-pyrazolo[3,4-c]pyridazine

Conditions

Temperature
60 °C

Procedure

A suspension of 1-methyl-5-phenyl-3-(pyrrolidin-1-yl)-1H-pyrazolo[3,4-c]pyridazin-4-ol (117 mg) in POCl3 (1.9 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 chromatography on silica gel to give the title compound (81 mg).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customthe residue was partitioned between CH2Cl2 and sat. aq. NaHCO3 solution
  3. customThe layers were separated
  4. extractionthe aqueous was extracted with CH2Cl2
  5. dry with materialthe combined organics were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-fc4dc5b091d64af7a116c98ac448f108
Source dataset
uspto-grants-2016_01
Patent number
US09227976B2

Reaction notes

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