Potassium Carbonate → 2-(((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)oxy)methyl)benzaldehyde

HRID 1770809Notes

Reaction equation

HRID 1770809 reaction equation
Br[CH2:2][C:3]1[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=1[CH:5]=[O:6].[CH3:11][CH:12]([N:14]1[C:18]([C:19]2[C:24]([OH:25])=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:17][CH:16]=[N:15]1)[CH3:13].C(=O)([O-])[O-].[K+].[K+]>CC#N.O>[CH:12]([N:14]1[C:18]([C:19]2[C:24]([O:25][CH2:2][C:3]3[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=3[CH:5]=[O:6])=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:17][CH:16]=[N:15]1)([CH3:13])[CH3:11]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 112526172-(Bromomethyl)benzaldehydeHCID 1370131542-[1-(Propan-2-yl)-1H-pyrazol-5-yl]pyridin-3-ol

Product 1

HCID 904636592-(((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)oxy)methyl)benzaldehyde

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

Into a 50-mL round-bottom flask, was placed a solution of 2-(bromomethyl)benzaldehyde (150 mg, 0.75 mmol, 1.00 equiv) in CH3CN (25 mL). 2-[1-(Propan-2-yl)-1H-pyrazol-5-yl]pyridin-3-ol (150 mg, 0.74 mmol, 1.00 equiv), potassium carbonate (210 mg, 1.52 mmol, 2.00 equiv), and KI (40 mg, 0.30 equiv) were added to the reaction. The resulting solution was heated to reflux for 6 h, and then it was cooled to rt. The resulting solution was diluted with 20 mL of H2O, and then it was extracted with 3×20 mL of ethyl acetate. The combined organic layers were washed with 1×30 mL of brine and concentrated under vacuum. The crude product (200 mg) was purified by Prep-HPLC with the following conditions (Prep-HPLC-010): Column, SunFire Prep C18 OBD Column, 5 um, 19*150 mm, mobile phase, water with 0.05% TFA and MeCN (38.0% MeCN up to 55.0% in 8 min); Detector, nm. This provided 98.6 mg (41%) of 2-[([2-[1-(propan-2-yl)-1H-pyrazol-5-yl]pyridin-3-yl]oxy)methyl]benzaldehyde as a light yellow solid; 1HNMR (300 MHz, CDCl3, ppm): 10.01 (s, 1H), 8.43 (m, 1H), 7.88 (m, 1H), 7.86 (m, 1H), 7.61-7.79 (m, 6H), 6.61 (d, J=2.1 Hz, 1H), 5.60 (s, 2H), 4.69-4.78 (m, 1H), 1.46 (d, J=6.6 Hz, 6H); (ES, m/z): 322 [M+1]+.

Workup

  1. customInto a 50-mL round-bottom flask, was placed
  2. temperatureThe resulting solution was heated
  3. temperatureto reflux for 6 h
  4. extractionit was extracted with 3×20 mL of ethyl acetate
  5. washThe combined organic layers were washed with 1×30 mL of brine
  6. concentrationconcentrated under vacuum
  7. customThe crude product (200 mg) was purified by Prep-HPLC with the following conditions (Prep-HPLC-010)

Sources & evidence

ORD record
ord-74869491b6b7438da73a836f44bad16f
Source dataset
uspto-grants-2016_02
Patent number
US09248199B2

Reaction notes

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