Ammonium Hydroxide → 1-ethyl-4-chloro-6-bromo-1H-pyrazolo[3,4-b]quinoline

HRID 375895Notes

Reaction equation

HRID 375895 reaction equation
[CH2:1]([N:3]1[C:7]([NH:8][C:9]2[C:10](=[CH:14][CH:15]=[CH:16][C:17]=2[Br:18])[C:11](O)=O)=[CH:6][CH:5]=[N:4]1)[CH3:2].[CH2:19]([N:21]1[C:25]([NH:26][C:27]2[C:28](=[CH:32][C:33]([Br:36])=[CH:34][CH:35]=2)[C:29](O)=O)=[CH:24][CH:23]=[N:22]1)[CH3:20].[NH4+].[OH-].O=P(Cl)(Cl)[Cl:41]>>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]3[C:10]([C:11]([Cl:41])=[C:6]2[CH:5]=[N:4]1)=[CH:14][CH:15]=[CH:16][C:17]=3[Br:18])[CH3:2].[CH2:19]([N:21]1[C:25]2=[N:26][C:27]3[C:28]([C:29]([Cl:41])=[C:24]2[CH:23]=[N:22]1)=[CH:32][C:33]([Br:36])=[CH:34][CH:35]=3)[CH3:20]

Participants

6

Reactant 4

HCID 14923Ammonium HydroxideHCID 24813Phosphorus oxychlorideHCID 19592213N-(1-ethylpyrazol-5-yl)-5-bromoanthranilic acidHCID 21217718N-(1-ethylpyrazol-5-yl)-3-bromoanthranilic acid

Product 2

HCID 195922191-ethyl-4-chloro-6-bromo-1H-pyrazolo[3,4-b]quinolineYield 64%HCID 212176931-ethyl-4-chloro-8-bromo-1H-pyrazolo[3,4-b]quinoline

Procedure

A mixture of N- (1-ethylpyrazol-5-yl)-3-bromoanthranilic acid and N-(1-ethylpyrazol-5-yl)-5-bromoanthranilic acid (34.8 g, 0.11 mol) and POCl3 (100 mL) was heated at reflux for 8 hours. The reaction mixture was cooled to room temperature and then was poured into ice-water and neutralized with concentrated NH4OH. The mixture was extracted with CH2Cl2 and the CH2Cl2 layer was dried over MgSO4 and evaporated to dryness. The residue was purified by column chromatography on silica gel eluting with CH2Cl2 /ether (9/1) to afford 2.7 g of 1-ethyl-4-chloro-8-bromo-1H-pyrazolo[3,4-b]quinoline (labelled as Example 44 (b)) and 22.5 g (64%) of 1-ethyl-4-chloro-6-bromo-1H-pyrazolo[3,4-b]quinoline (labelled as Example 44 (c)).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 8 hours
  3. extractionThe mixture was extracted with CH2Cl2
  4. dry with materialthe CH2Cl2 layer was dried over MgSO4
  5. customevaporated to dryness
  6. customThe residue was purified by column chromatography on silica gel eluting with CH2Cl2 /ether (9/1)

Sources & evidence

ORD record
ord-401dc20c02174788aad2837a6a965423
Source dataset
uspto-grants-1996_01
Patent number
US05488055

Reaction notes

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