Potassium Carbonate → HCID 86303715, compound

HRID 1484825Notes

Reaction equation

HRID 1484825 reaction equation
Cl[CH2:2][C:3]1[C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([Cl:15])[CH:10]=2)=[N:5][CH:6]=[CH:7][CH:8]=1.[OH:16][C:17]1[C:18]([CH:25]=[O:26])=[CH:19][C:20]([O:23][CH3:24])=[N:21][CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>CC#N>[Cl:15][C:11]1[CH:10]=[C:9]([C:4]2[C:3]([CH2:2][O:16][C:17]3[C:18]([CH:25]=[O:26])=[CH:19][C:20]([O:23][CH3:24])=[N:21][CH:22]=3)=[CH:8][CH:7]=[CH:6][N:5]=2)[CH:14]=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 722124985-Hydroxy-2-methoxyisonicotinaldehydeHCID 90416855HCID 90416855, compound

Product 1

HCID 86303715HCID 86303715, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

Into a 50-mL round-bottom flask, was placed a solution of 3-(chloromethyl)-2-(3-chlorophenyl)pyridine (309 mg, 1.30 mmol, 1.00 equiv), 5-hydroxy-2-methoxypyridine-4-carbaldehyde (200 mg, 1.31 mmol, 1.00 equiv), and potassium carbonate (361 mg, 2.61 mmol, 2.00 equiv) in CH3CN (20 mL). The resulting solution was stirred for 4 h at 70° C., and then it was concentrated under vacuum. The crude product (300 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 (20.0% MeCN up to 60.0% in 10 min, up to 95.0% in 2 min, down to 20.0% in 1 min); Detector, Waters 2545 UvDector 254 & 220 nm. This resulted in 71 mg (9%) of 5-[[2-(3-chlorophenyl)pyridin-3-yl]methoxy]-2-methoxypyridine-4-carbaldehyde; bis(trifluoroacetic acid) as a yellow solid. 1HNMR (400 MHz, DMSO-d6) δ 10.07 (s, 1H), 8.72 (m, 1H), 8.20 (m, 2H), 7.79 (s, 1H), 7.60 (m, 4H), 6.95 (m, 1H), 5.21 (m, 2H), 3.85 (s, 3H); MS (ESI) m/z 355 [M+H]+.

Workup

  1. customInto a 50-mL round-bottom flask, was placed
  2. concentrationit was concentrated under vacuum
  3. customThe crude product (300 mg) was purified by Prep-HPLC with the following conditions (Prep-HPLC-010)
  4. waitmobile phase, water with 0.05% TFA and MeCN (20.0% MeCN up to 60.0% in 10 min
  5. waitup to 95.0% in 2 min
  6. waitdown to 20.0% in 1 min)
  7. customThis resulted in 71 mg (9%) of 5-[[2-(3-chlorophenyl)pyridin-3-yl]methoxy]-2-methoxypyridine-4-carbaldehyde

Sources & evidence

ORD record
ord-2ba104994dee487c8432951ad82bb7ed
Source dataset
uspto-grants-2016_08
Patent number
US09422279B2

Reaction notes

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