Hydrochloric Acid → HCID 178434426, compound

HRID 1526137Notes

Reaction equation

HRID 1526137 reaction equation
C([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:24]3[C:23](=[O:25])[NH:22][C:21]4[CH:26]=[C:27]([N:30]5[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]5)[CH:28]=[CH:29][C:20]=4[C:19]=3[C:18]3[C:36]([CH3:48])=[N:37][N:38](CC4C=CC(OC)=CC=4)[C:17]=3[N:16]=2)=[CH:11][C:10]=1[C:49]([F:52])([F:51])[F:50])C1C=CC=CC=1.C(OC(C)C)(C)C.[ClH:60].O1CCOCC1>FC(F)(F)C(O)=O>[ClH:60].[OH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:24]3[C:23](=[O:25])[NH:22][C:21]4[CH:26]=[C:27]([N:30]5[CH2:31][CH2:32][NH:33][CH2:34][CH2:35]5)[CH:28]=[CH:29][C:20]=4[C:19]=3[C:18]3[C:36]([CH3:48])=[N:37][NH:38][C:17]=3[N:16]=2)=[CH:11][C:10]=1[C:49]([F:52])([F:51])[F:50]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7914Diisopropyl EtherHCID 312751,4-DioxaneHCID 136338246HCID 136338246, compound

Product 1

HCID 178434426HCID 178434426, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 1.8 g (2.55 mmol) of 5-(4-(benzyloxy)-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 3 hours. After returning to room temperature, 50 ml of diisopropyl ether is added until a stable precipitate appears; the latter is filtered and then taken up in water. Acidity is neutralized by the addition of 1 M soda. The solid is filtered again and then triturated several times in hot methanol to yield after a final filtration 950 mg of 5-(4-hydroxy-3-(trifluoromethyl)phenyl)-1-methyl-9-(piperazin-1-yl)-3H-benzo[f]pyrazolo[3,4-c][2,7]naphthyridin-6(7H)-one. The product is then taken up in 20 ml of anhydrous dioxane; a 4 M solution of hydrochloric acid in dioxane (932 μl, 3.73 mmol) is added and the reaction medium is stirred at room temperature for 2 hours. The precipitate is filtered, rinsed with dioxane and triturated in methanol to yield 475 mg (36%) of 5-(4-hydroxy-3-(trifluoromethyl)phenyl)-1-methyl-9-(piperazin-1-yl)-3H-benzo[f]pyrazolo[3,4-c][2,7]naphthyridin-6(7H)-one hydrochloride in the form of a yellow solid.

Workup

  1. customAfter returning to room temperature
  2. filtrationthe latter is filtered
  3. additionAcidity is neutralized by the addition of 1 M soda
  4. filtrationThe solid is filtered again
  5. customtriturated several times in hot methanol
  6. customto yield after a final
  7. filtrationfiltration 950 mg of 5-(4-hydroxy-3-(trifluoromethyl)phenyl)-1-methyl-9-(piperazin-1-yl)-3H-benzo[f]pyrazolo[3,4-c][2,7]naphthyridin-6(7H)-one
  8. filtrationThe precipitate is filtered
  9. washrinsed with dioxane
  10. customtriturated in methanol

Sources & evidence

ORD record
ord-65cdc6fdd02b4e19bf4dad8742c5d8ec
Source dataset
uspto-grants-2015_07
Patent number
US09085575B2

Reaction notes

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