Ethyl Acetate → HCID 118252987, compound

HRID 1770791Notes

Reaction equation

HRID 1770791 reaction equation
[OH:1][C:2]1[C:10]([CH:11]=[O:12])=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[CH:4][CH:3]=1.[Cl-].Cl[CH2:15][C:16]1[C:17]([C:22]2[N:26]([CH:27]([CH3:29])[CH3:28])[N:25]=[CH:24][CH:23]=2)=[NH+:18][CH:19]=[CH:20][CH:21]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CN(C)C=O.O>[CH:27]([N:26]1[C:22]([C:17]2[C:16]([CH2:15][O:1][C:2]3[C:10]([CH:11]=[O:12])=[C:9]4[C:5]([CH:6]=[N:7][NH:8]4)=[CH:4][CH:3]=3)=[CH:21][CH:20]=[CH:19][N:18]=2)=[CH:23][CH:24]=[N:25]1)([CH3:29])[CH3:28]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 137024750HCID 137024750, compoundHCID 178456635HCID 178456635, compound

Product 1

HCID 118252987HCID 118252987, compoundYield 51.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

6-Hydroxy-1H-indazole-7-carbaldehyde (0.14 g, 0.86 mmol, 1 eq.) was dissolved in N,N-dimethylformamide (4 ml). 3-(Chloromethyl)-2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-1-ium chloride (0.235 g, 0.86 mmol, 1 eq.) and potassium carbonate (0.36 g, 2.6 mmol, 3 eq.) were added and the reaction mixture was stirred in a 50° C. heat block for 16 h. The reaction mixture was then cooled, and ethyl acetate (100 ml) and water (50 ml) were added. The phases were separated and the aqueous phase was extracted with more ethyl acetate (2×50 ml). The combined organic phases were washed with water (50 ml) and aqueous saturated sodium chloride solution (50 ml), and dried over sodium sulfate. After concentration the residue was purified by silica gel chromatography (5-70% ethyl acetate/hexanes). Product fractions were triturated with diethyl ether and lyophilized from acetonitrile/water to give 6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)-1H-indazole-7-carbaldehyde (0.16 g, 51%) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 11.59 (s, 1H), 10.58 (s, 1H), 8.74 (dd, J=4.4, 1.6 Hz, 1H), 8.02 (d, J=1.6 Hz, 1H), 8.01 (s, 1H), 7.90 (d, J=8.8 Hz, 1H), 7.58 (d, J=1.8 Hz, 1H), 7.42 (dd, J=7.9, 4.8 Hz, 1H), 6.75 (d, J=8.8 Hz, 1H), 6.36 (d, J=1.8 Hz, 1H), 5.22 (s, 2H), 4.66 (septet, J=6.6 Hz, 1H), 1.46 (d, J=6.6 Hz, 6H). MS (ESI) m/z 362 [M+H]+.

Workup

  1. temperatureheat block for 16 h
  2. temperatureThe reaction mixture was then cooled
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with more ethyl acetate (2×50 ml)
  5. washThe combined organic phases were washed with water (50 ml) and aqueous saturated sodium chloride solution (50 ml)
  6. dry with materialdried over sodium sulfate
  7. concentrationAfter concentration the residue
  8. customwas purified by silica gel chromatography (5-70% ethyl acetate/hexanes)
  9. customProduct fractions were triturated with diethyl ether

Sources & evidence

ORD record
ord-d9b3469e7c5f4aa4996c6c49539ae65a
Source dataset
uspto-grants-2016_02
Patent number
US09248199B2

Reaction notes

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