Trifluoroacetic acid → Trifluoroacetic acid

HRID 2360695Notes

Reaction equation

HRID 2360695 reaction equation
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[CH:3]([NH2:9])[CH2:2]2.[CH2:10]([C:12]1[C:20]2[C:19]([C:21](O)=[O:22])=[CH:18][C:17]([C:24]3[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=3)=[N:16][C:15]=2[NH:14][N:13]=1)[CH3:11].[B-](F)(F)(F)F.CCOC(C(C#N)=NOC(N(C)C)=[N+](C)C)=O.[C:53]([OH:59])([C:55]([F:58])([F:57])[F:56])=[O:54]>CN(C=O)C.CN1CCOCC1>[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[CH:3]([NH:9][C:21]([C:19]1[C:20]3[C:12]([CH2:10][CH3:11])=[N:13][NH:14][C:15]=3[N:16]=[C:17]([C:24]3[CH:25]=[CH:26][C:27]([OH:30])=[CH:28][CH:29]=3)[CH:18]=1)=[O:22])[CH2:2]2.[C:53]([OH:59])([C:55]([F:58])([F:57])[F:56])=[O:54]

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 1232383-AminoquinuclidineHCID 2733286O-[(Ethoxycarbonyl)cyanomethylenamino]-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 178438022HCID 178438022, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 178438021HCID 178438021, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 79724-MethylmorpholineSolvent

Procedure

To a solution of 1-aza-bicyclo[2.2.2]oct-3-ylamine (17 mg, 0.135 mmol) in 1 mL of DMF, N-methyl morpholine was added (42 mg, 0.42 mmol) followed by 3-ethyl-6-(4-hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (34 mg, 0.12 mmol) dissolved in 0.5 mL of DMF. Then a solution of TOTU (43 mg, 0.13 mmol) in 0.5 mL DMF was added and the mixture stirred at r.t. over the weekend. The mixture was treated with 0.1 mL TFA, filtered off and purified by prep. HPLC to obtain the desired product 3-ethyl-6-(4-hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (1-aza-bicyclo[2.2.2]oct-3-yl)-amide as TFA salt. In order to change from TFA salt to HCl salt and deprotection (for compounds bearing BOC-protecting groups) the compound was dissolved in 2 mL of 5-6M HCl iPrOH and the reaction was stirred at r.t. overnight. Then 10 mL of water were added and the mixture was freezed dried to give the desired product 3-ethyl-6-(4-hydroxy-phenyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (1-aza-bicyclo[2.2.2]oct-3-yl)-amide as hydrochloride salt (12.7 mg, 23%).

Workup

  1. filtrationfiltered off
  2. custompurified by prep

Sources & evidence

ORD record
ord-25ca84a44300453c9b921d49c9f1e87d
Source dataset
uspto-grants-2014_04
Patent number
US08686150B2

Reaction notes

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