Toluene → HCID 86686662, compound

HRID 2404241Notes

Reaction equation

HRID 2404241 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:21]3[C:20]4[CH:19]=[C:18]([O:22][CH:23]([C:27]5[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=5)[C:24](O)=[O:25])[C:17]([O:34][CH3:35])=[CH:16][C:15]=4[N:14]=[CH:13][C:12]=3[N:11]([CH3:36])[N:10]=2)=[CH:5][CH:4]=1)#[N:2].C1(C)C=CC=CC=1.S(Cl)([Cl:46])=O>>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:21]3[C:20]4[CH:19]=[C:18]([O:22][CH:23]([C:27]5[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=5)[C:24]([Cl:46])=[O:25])[C:17]([O:34][CH3:35])=[CH:16][C:15]=4[N:14]=[CH:13][C:12]=3[N:11]([CH3:36])[N:10]=2)=[CH:5][CH:4]=1)#[N:2]

Participants

4

Reactant 3

HCID 1140TolueneHCID 24386Thionyl ChlorideHCID 56592772HCID 56592772, compound

Product 1

HCID 86686662HCID 86686662, compound

Procedure

[1-(4-Cyanophenyl)-7-methoxy-3-methyl-3H-pyrazolo[3,4-c]quinolin-8-yloxy]-(4-fluorophenyl)acetic acid (190 mg, 394 μmol) is dissolved in thionyl chloride (2.0 ml) and heated under reflux for 2 h. The mixture is then evaporated to dryness in vacuo and co-evaporated twice with distilled, anhydrous toluene, giving [1-(4-cyanophenyl)-7-methoxy-3-methyl-3H-pyrazolo[3,4-c]quinolin-8-yloxy]-(4-fluorophenyl)acetyl chloride (195 mg, 389 μmol). 35 mg (69.9 μmol) of the acid chloride obtained are subsequently dissolved in anhydrous N,N-dimethylformamide (2.0 ml) in a dry nitrogen atmosphere, and 2-(4-ethylpiperazin-1-yl)-ethylamine (22 mg, 140 μmol) is added with ice-bath cooling. The reaction solution is stirred at room temperature for 2 h. The mixture is then poured into water (30 ml) and extracted four times with ethyl acetate (30 ml each time). The combined organic phases are washed twice with water (20 ml each time), subsequently dried using Na2SO4, filtered with suction, and the filtrate is evaporated to dryness in vacuo. The residue is dissolved in dimethyl sulfoxide and chromatographed (pHPLC, solvent gradient water/1-30% by vol. of acetonitrile, 0.1% by vol. of formic acid), giving, after freeze-drying, the title compound 2-[1-(4-cyanophenyl)-7-methoxy-3-methyl-3H-pyrazolo[3,4-c]quinolin-8-yloxy]-N-[2-(4-ethylpiperazin-1-yl)ethyl]-2-(4-fluorophenyl)acetamide (21 mg, 33.8 μmol) as lyophilisate having a melting range of 110-112° C. MS: 622.3 (M+H+), TLC (HPTLC): Rf=0.40 (methanol/Hünig's base 99:1, parts by volume).

Workup

  1. temperatureheated
  2. temperatureunder reflux for 2 h
  3. customThe mixture is then evaporated to dryness in vacuo
  4. distillationwith distilled

Sources & evidence

ORD record
ord-88fcbc082c0c4ccfbc68a7d8387864b9
Source dataset
uspto-grants-2014_08
Patent number
US08802712B2

Reaction notes

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