Potassium Iodide → 4-Chloro-3-[2-methyl-5-(5-methyl-[1,3,4]oxadiazol-2-yl)-phenoxymethyl]-thieno[3,2-c]pyridine-7-carboxylic acid ethyl ester

HRID 1671531Notes

Reaction equation

HRID 1671531 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7]2[S:15][CH:14]=[C:13]([CH2:16]Br)[C:8]=2[C:9]([Cl:12])=[N:10][CH:11]=1)=[O:5])[CH3:2].[I-].[K+].[CH3:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[O:28][C:29]([CH3:32])=[N:30][N:31]=2)=[CH:23][C:22]=1[OH:33].C(=O)([O-])[O-].[K+].[K+].C1OCCOCCOCCOCCOCCOC1>CN(C)C=O>[CH2:1]([O:3][C:4]([C:6]1[C:7]2[S:15][CH:14]=[C:13]([CH2:16][O:33][C:22]3[CH:23]=[C:24]([C:27]4[O:28][C:29]([CH3:32])=[N:30][N:31]=4)[CH:25]=[CH:26][C:21]=3[CH3:20])[C:8]=2[C:9]([Cl:12])=[N:10][CH:11]=1)=[O:5])[CH3:2]

Participants

7

Reactant 5

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 2855718-Crown-6HCID 115300973-Bromomethyl-4-chloro-thieno[3,2-c]pyridine-7-carboxylic acid ethyl esterHCID 596497212-Methyl-5-(5-methyl-[1,3,4]oxadiazol-2-yl)-phenol

Product 1

HCID 248007954-Chloro-3-[2-methyl-5-(5-methyl-[1,3,4]oxadiazol-2-yl)-phenoxymethyl]-thieno[3,2-c]pyridine-7-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

A suspension of 3-bromomethyl-4-chloro-thieno[3,2-c]pyridine-7-carboxylic acid ethyl ester (0.29 g, 0.87 mmol) (from Example 1 supra), potassium iodide (0.14 g, 0.87 mmol), 2-methyl-5-(5-methyl-[1,3,4]oxadiazol-2-yl)-phenol (0.17 g, 0.9 mmol) (from Example 34 supra), potassium carbonate (0.27 g, 1.9 mmol) and 18-Crown-6 (10 mg, 0.04 mmol) (Aldrich) in N,N-dimethylformamide (5 mL) was heated at 65° C. in a sealed tube with magnetic stirring for 20 hours. After cooling, mixture was partitioned between ethyl acetate (2×100 mL) and water (2×100 mL). Aqueous layers were extracted with dichloromethane (2×100 mL). [Material was more soluble in dichloromethane than ethyl acetate.] Organic layers were washed with brine, then combined, dried (MgSO4), filtered and concentrated. Residue was purified by flash chromatography (Biotage 40S, dichloromethane then 20% ethyl acetate in dichloromethane as solvent) to give 4-chloro-3-[2-methyl-5-(5-methyl-[1,3,4]oxadiazol-2-yl)-phenoxymethyl]-thieno[3,2-c]pyridine-7-carboxylic acid ethyl ester as a white powder. (Yield 0.24 g, 62.4%).

Workup

  1. temperatureAfter cooling
  2. custommixture was partitioned between ethyl acetate (2×100 mL) and water (2×100 mL)
  3. extractionAqueous layers were extracted with dichloromethane (2×100 mL)
  4. wash] Organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customResidue was purified by flash chromatography (Biotage 40S, dichloromethane

Sources & evidence

ORD record
ord-20e62c1411044c2eb857429afc0030e3
Source dataset
uspto-grants-2011_08
Patent number
US07994321B2

Reaction notes

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