Trifluoroacetic acid → HCID 178488911, compound

HRID 1526135Notes

Reaction equation

HRID 1526135 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:18]3[C:17](=[O:19])[NH:16][C:15]4[CH:20]=[C:21]([N:24]5[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]5)[CH:22]=[CH:23][C:14]=4[C:13]=3[C:12]3[C:30]([CH3:42])=[N:31][N:32](CC4C=CC(OC)=CC=4)[C:11]=3[N:10]=2)=[CH:5][C:4]=1C(F)(F)F.C(OC(C)C)(C)C.[F:54][C:55]([F:60])([F:59])[C:56]([OH:58])=[O:57]>>[F:54][C:55]([F:60])([F:59])[C:56]([OH:58])=[O:57].[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:18]3[C:17](=[O:19])[NH:16][C:15]4[CH:20]=[C:21]([N:24]5[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]5)[CH:22]=[CH:23][C:14]=4[C:13]=3[C:12]3[C:30]([CH3:42])=[N:31][NH:32][C:11]=3[N:10]=2)=[CH:5][CH:4]=1

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7914Diisopropyl EtherHCID 136338243HCID 136338243, compound

Product 1

HCID 178488911HCID 178488911, compound

Procedure

A solution of 3 g (4.77 mmol) of 5-(4-methoxy-3-(trifluoromethyl)phenyl)-3-(4-methoxybenzyl)-1-methyl-9-(piperazin-1-yl)-3H-benzo[f]pyrazolo[3,4-c][2,7]naphthyridin-6(7H)-one dissolved in 25 ml of trifluoroacetic acid is carried at 70° C. for 4 hours and then cooled to room temperature before the addition of isopropyl ether (50 ml). The reaction medium is stirred at room temperature for 30 minutes and then the precipitate obtained is filtered to yield 5-(4-methoxyphenyl)-1-methyl-9-(piperazin-1-yl)-3H-benzo[f]pyrazolo[3,4-c][2,7]naphthyridin-6(7H)-one trifluoroacetate. The solid is dissolved in 40 ml of anhydrous dichloroethane. The reaction medium is cooled to 0° C. before the slow addition of 30.3 ml (30.3 mmol) of a 1 M solution of boron tribromide in dichloromethane. The reaction medium is carried at reflux for 20 hours with the regular addition of a cold 1 M solution of boron tribromide in dichloromethane (30.3 ml, 30.3 mmol additional in total) until the reaction is quenched. Methanol (roughly 100 ml) is added and then the reaction medium is stirred for 2 hours. The solvents are concentrated. Saturated aqueous NaHCO3 solution is added and the aqueous phase is washed with ethyl acetate. The aqueous phase is evaporated and then purified by silica gel chromatography (eluent: 60:14:24:2 dichloromethane/methanol/cyclohexane/ammonium hydroxide to pure methanol) to yield 150 mg (12.5%) of 2-hydroxy-5-(1-methyl-6-oxo-9-(piperazin-1-yl)-6,7-dihydro-3H-benzo[f]pyrazolo[3,4-c][2,7]naphthyridin-5-yl)benzoic acid hydrochloride in the form of a yellow solid.

Workup

  1. customthe precipitate obtained
  2. filtrationis filtered

Sources & evidence

ORD record
ord-55a98409f2664cc1a0d3220cfbf465f5
Source dataset
uspto-grants-2015_07
Patent number
US09085575B2

Reaction notes

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