4-Fluorobenzoic Acid → HCID 178436916, compound

HRID 340011Notes

Reaction equation

HRID 340011 reaction equation
Br.Br.Br.[CH2:4]([C:6]1[C:7]([C:14]2[CH:22]=[C:21]3[C:17]([C:18]([C:23]4[NH:24][C:25]5[CH2:30][CH2:29][NH:28][CH2:27][C:26]=5[N:31]=4)=[N:19][NH:20]3)=[CH:16][CH:15]=2)=[CH:8][C:9]([F:13])=[C:10]([OH:12])[CH:11]=1)[CH3:5].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[F:65][C:66]1[CH:74]=[CH:73][C:69]([C:70](O)=[O:71])=[CH:68][CH:67]=1.C(=O)([O-])O.[Na+]>CN(C=O)C>[CH2:4]([C:6]1[CH:11]=[C:10]([OH:12])[C:9]([F:13])=[CH:8][C:7]=1[C:14]1[CH:22]=[C:21]2[C:17]([C:18]([C:23]3[NH:24][C:25]4[CH2:30][CH2:29][N:28]([C:70]([C:69]5[CH:73]=[CH:74][C:66]([F:65])=[CH:67][CH:68]=5)=[O:71])[CH2:27][C:26]=4[N:31]=3)=[N:19][NH:20]2)=[CH:16][CH:15]=1)[CH3:5]

Participants

7

Reactant 5

HCID 99734-Fluorobenzoic AcidHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 1784192405-Ethyl-2-fluoro-4-[3-(4,5,6,7-tetrahydro-1H-imidazol[4,5-c]pyridin-2-yl)-1H-indazol-6-yl]-phenol trihydrobromide salt

Product 1

HCID 178436916HCID 178436916, compoundYield 19.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-ethyl-2-fluoro-4-[3-(4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-2-yl)-1H-indazol-6-yl]-phenol trihydrobromide salt (Preparation 25, 50 mg, 80 μmol) in DMF (1 mL), was added HATU (32 mg, 84 μmol), and DIPEA (56 μL, 320 μmol). The reaction mixture was stirred at room temperature for 30 minutes. 4-Fluoro-benzoic acid (11.2 mg, 80 μmol) was added to the reaction mixture and stirring was continued for 18 hours. Saturated aqueous sodium hydrogen carbonate solution (5 mL) was added to the reaction mixture. The resulting solid was collected by filtration, washing with further saturated aqueous sodium hydrogen carbonate solution. The crude material was purified by HPLC Method B to afford 7.7 mg of the title compound.

Workup

  1. stirringstirring
  2. waitwas continued for 18 hours
  3. filtrationThe resulting solid was collected by filtration
  4. washwashing with further saturated aqueous sodium hydrogen carbonate solution
  5. customThe crude material was purified by HPLC Method B

Sources & evidence

ORD record
ord-cc613c61071449168426277c4548fc4a
Source dataset
uspto-grants-2014_11
Patent number
US08895544B2

Reaction notes

Loading…