Water → 7-Chloro-2-[4-(dimethylamino)phenyl]thieno[3,2-b]pyridine-6-carbonitrile

HRID 1611497Notes

Reaction equation

HRID 1611497 reaction equation
[Cl:1][C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]2[CH:10]=[C:11](I)[S:12][C:3]=12.[CH3:14][N:15]([CH3:25])[C:16]1[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][CH:17]=1.O>COCCOC.C(=O)(O)[O-].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]2[CH:10]=[C:11]([C:19]3[CH:20]=[CH:21][C:16]([N:15]([CH3:25])[CH3:14])=[CH:17][CH:18]=3)[S:12][C:3]=12

Participants

7

Reactant 3

HCID 962WaterHCID 27343444-(Dimethylamino)phenylboronic acid2×HCID 99961437-Chloro-2-iodothieno[3,2-B]pyridine-6-carbonitrile

Product 1

HCID 222566127-Chloro-2-[4-(dimethylamino)phenyl]thieno[3,2-b]pyridine-6-carbonitrileYield 60%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 80711,2-DimethoxyethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of 7-chloro-2-iodothieno[3,2-b]pyridine-6-carbonitrile (321 mg, 1.0 mmol), 4-(dimethylamino)phenylboronic acid (248 mg, 1.5 mmol) and 58 mgs of tetrakis(triphenylphosphine)palladium(0) in 13 mL of ethylene glycol dimethyl ether and 11 mL of aqueous saturated sodium bicarbonate is heated at reflux for 6 hours. 4-(dimethylamino)phenylboronic acid (105 mg) and tetrakis(triphenylphosphine)palladium(0) (29 mg) are added and the reaction mixture is heated at reflux for 6 hours. The mixture is treated with water and extracted into dichloromethane and the organic phase is washed with brine and dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with a gradient of dichloromethane to 2% ethyl acetate in dichloromethane to provide 187 mg (60%) of 7-chloro-2-[4-(dimethylamino)phenyl]thieno[3,2-b]pyridine-6-carbonitrile as an orange solid, mp 270-272° C.; 1H NMR (CDCl3) δ 3.07 (s, 6H), 6.73 (d, J=5 Hz, 2H), 7.58 (s, 1H), 7.63 (d, J=5 Hz, 2H), 8.74 (s, 1H); HRMS found: 314.05127.

Workup

  1. temperatureis heated
  2. temperatureat reflux for 6 hours
  3. temperaturethe reaction mixture is heated
  4. temperatureat reflux for 6 hours
  5. extractionextracted into dichloromethane
  6. washthe organic phase is washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue is purified by flash column chromatography
  11. washeluting with a gradient of dichloromethane to 2% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-07997cde982d433cbe60eb34c7e15c06
Source dataset
uspto-grants-2006_01
Patent number
US06987116B2

Reaction notes

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