Hydrochloric Acid → 2-methoxy-5-((2-(4-methyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde

HRID 1471697Notes

Reaction equation

HRID 1471697 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:8]([O:11][CH2:12][C:13]2[C:14]([C:19]3[N:23](C4CCCCO4)[N:22]=[CH:21][C:20]=3[CH3:30])=[N:15][CH:16]=[CH:17][CH:18]=2)=[CH:9][N:10]=1)[CH:6]=[O:7].Cl>CCO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:8]([O:11][CH2:12][C:13]2[C:14]([C:19]3[NH:23][N:22]=[CH:21][C:20]=3[CH3:30])=[N:15][CH:16]=[CH:17][CH:18]=2)=[CH:9][N:10]=1)[CH:6]=[O:7]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 866907482-methoxy-5-((2-(4-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde

Product 1

HCID 854728692-methoxy-5-((2-(4-methyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehydeYield 46%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To 2-methoxy-5-((2-(4-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde (110 mg, 0.27 mmol, 1 equiv) suspended in EtOH (1 mL) was added HCl (1.0 mL, 3 N). The solution turned homogeneous and the mixture was stirred at rt overnight. The EtOH was partially removed by blowing in N2 gas and basified to pH 9. The aqueous solution was extracted with EtOAc three times. The organic layer was dried over Na2SO4 and concentrated. The crude was purified on silica gel using a mixture of MeOH and DCM as eluent to give 2-methoxy-5-((2-(4-methyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde (40 mg, 46%) as a white solid. 1H NMR (400 MHz; CDCl3) δ=10.45 (s, 1H), 8.76 (d, 1H), 8.07 (br, 1H), 8.05 (s, 1H), 7.53 (s, 1H), 7.40 (dd, 1H), 7.13 (s, 1H), 5.52 (br, 2H), 3.98 (s, 3H). LRMS (MAT) m/z 325.1.

Workup

  1. customThe EtOH was partially removed
  2. extractionThe aqueous solution was extracted with EtOAc three times
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated
  5. customThe crude was purified on silica gel using
  6. additiona mixture of MeOH and DCM as eluent

Sources & evidence

ORD record
ord-7152d0a9d70549eaa624aefe15b3372f
Source dataset
uspto-grants-2015_04
Patent number
US09012450B2

Reaction notes

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