Hydrochloric Acid → 1-[(4-fluorophenyl)methyl]-N-hydroxy-N-methyl-pyrazolo[3,4-c]pyridine-5-carboxamide

HRID 2377072Notes

Reaction equation

HRID 2377072 reaction equation
[NH:1]1[C:5]2=[CH:6][N:7]=[C:8]([C:10]([O:12]C)=O)[CH:9]=[C:4]2[CH:3]=[N:2]1.[Li+].[OH-].Cl.Cl.[CH3:18][NH:19][OH:20].C(N([CH2:26][CH3:27])CC)C.CN(C(ON1N=N[C:38]2[CH:39]=[CH:40][CH:41]=N[C:37]1=2)=[N+](C)C)C.[F:45][P-](F)(F)(F)(F)F>CO.C(OCC)C.O>[F:45][C:41]1[CH:40]=[CH:39][C:38]([CH2:37][N:1]2[C:5]3=[CH:6][N:7]=[C:8]([C:10]([N:19]([OH:20])[CH3:18])=[O:12])[CH:9]=[C:4]3[CH:3]=[N:2]2)=[CH:27][CH:26]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 8471TriethylamineHCID 77906N-methylhydroxylamine hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59855813Methyl 1H-pyrazolo[3,4-C]pyridine-5-carboxylate

Product 1

HCID 159570531-[(4-fluorophenyl)methyl]-N-hydroxy-N-methyl-pyrazolo[3,4-c]pyridine-5-carboxamideYield 100%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 3283Diethyl EtherSolvent

Procedure

To a stirring solution of methyl 1H-pyrazolo[3,4-c]pyridine-5-carboxylate (100 mg, 0.351 mmol) in methanol (4 mL) was added a 3.0 M solution of LiOH in water (0.351 mL, 1.05 mmol) and the mixture was stirred overnight, then 1.0 M hydrochloric acid in diethyl ether was added (1.05 mL, 1.05 mmol) and the solvent was evaporated under reduced pressure. The crude solid was dissolved in DMF and N-methylhydroxylamine hydrochloride (58 mg, 0.698 mmol) was added followed by triethylamine (214 mL, 1.154 mmol) and HATU (266 mg, 0.698 mmol). The mixture was stirred overnight. Water was added and the mixture was extracted with dichloromethane (3×20 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated. The crude solid was dissolved in DMSO and purified by reverse phase preparative HPLC to provide a white solid (105 mg, 100% yield). 1H NMR (DMSO-d6): & 10.24 (bs, 1H), 9.26 (s, 1H), 8.07 (s, 1H), 7.37 (m, 2H), 7.15 (m, 2H), 5.81 (s, 2H), 3.31 (s, 3H). Anal. HPLC: >95% (@ 254, 222 nM). HRMS calcd for C15H13FN4O2 (M+H) 301.1088, found 301.1096.

Workup

  1. customthe solvent was evaporated under reduced pressure
  2. dissolutionThe crude solid was dissolved in DMF
  3. stirringThe mixture was stirred overnight
  4. extractionthe mixture was extracted with dichloromethane (3×20 mL)
  5. dry with materialThe combined organic extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionThe crude solid was dissolved in DMSO
  9. custompurified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-6166b0edfa184ecca3bd6dfd6bcccd09
Source dataset
uspto-grants-2008_12
Patent number
US07468375B2

Reaction notes

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