Potassium Carbonate → 5-((5-(1-isopropyl-1H-pyrazol-5-yl)-3,6-dihydro-2H-pyran-4-yl)methoxy)-2-methoxyisonicotinaldehyde

HRID 1484792Notes

Reaction equation

HRID 1484792 reaction equation
Br[CH2:2][C:3]1[CH2:8][CH2:7][O:6][CH2:5][C:4]=1[C:9]1[N:13]([CH:14]([CH3:16])[CH3:15])[N:12]=[CH:11][CH:10]=1.[OH:17][C:18]1[C:23]([CH:24]=[O:25])=[CH:22][C:21]([O:26][CH3:27])=[N:20][CH:19]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O.CCOC(C)=O>[CH:14]([N:13]1[C:9]([C:4]2[CH2:5][O:6][CH2:7][CH2:8][C:3]=2[CH2:2][O:17][C:18]2[C:23]([CH:24]=[O:25])=[CH:22][C:21]([O:26][CH3:27])=[N:20][CH:19]=2)=[CH:10][CH:11]=[N:12]1)([CH3:16])[CH3:15]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 722124985-Hydroxy-2-methoxyisonicotinaldehydeHCID 904080795-(4-(bromomethyl)-5,6-dihydro-2H-pyran-3-yl)-1-isopropyl-1H-pyrazole

Product 1

HCID 863040155-((5-(1-isopropyl-1H-pyrazol-5-yl)-3,6-dihydro-2H-pyran-4-yl)methoxy)-2-methoxyisonicotinaldehydeYield 38.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-(4-(bromomethyl)-5,6-dihydro-2H-pyran-3-yl)-1-isopropyl-1H-pyrazole (50 mg, 0.19 mmol) (see the synthesis of Compound L) and 5-hydroxy-2-methoxyisonicotinaldehyde (30 mg, 0.23 mmol) in DMF (1 mL) was added K2CO3 (50 mg, 0.38 mmol). After stirred at room temperature for 3 h, it was diluted with water and EtOAc, organic layer was separated, and the aqueous layer was extracted with EtOAc, organic layer was combined, washed with brine, dried and concentrated to give crude product, which was purified by column (Hexanes/EtOAc=1:1) to give 5-((5-(1-isopropyl-1H-pyrazol-5-yl)-3,6-dihydro-2H-pyran-4-yl)methoxy)-2-methoxyisonicotinaldehyde (26 mg). 1H NMR (400 MHz, CDCl3) δ (ppm) 10.40 (s, 1H), 7.81 (s, 1H), 7.54 (d, J=1.6 Hz, 1H), 7.05 (s, 1H), 6.08 (d, J=1.6 Hz, 1H), 4.42 (s, 2H), 4.40 (m, 1H), 4.19 (s, 2H), 3.98 (t, J=5.6 Hz, 2H), 3.88 (s, 3H), 2.47 (s, 2H), 1.41 (d, J=6.8 Hz, 6H); MS (ESI) m/z 358.4 [M+H]+.

Workup

  1. customwas separated
  2. extractionthe aqueous layer was extracted with EtOAc, organic layer
  3. washwashed with brine
  4. customdried
  5. concentrationconcentrated
  6. customto give crude product, which
  7. customwas purified by column (Hexanes/EtOAc=1:1)

Sources & evidence

ORD record
ord-627f434c58f64021962a966f49aa77eb
Source dataset
uspto-grants-2016_08
Patent number
US09422279B2

Reaction notes

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