3,4,5-Trimethoxyaniline → HCID 10003428, compound

HRID 1611529Notes

Reaction equation

HRID 1611529 reaction equation
[CH3:1][O:2][C:3](=[O:19])[CH2:4][CH2:5][CH2:6][C:7]1[S:18][C:10]2=[N:11][CH:12]=[C:13]([C:16]#[N:17])[C:14](Cl)=[C:9]2[CH:8]=1.[CH3:20][O:21][C:22]1[CH:23]=[C:24]([CH:26]=[C:27]([O:31][CH3:32])[C:28]=1[O:29][CH3:30])[NH2:25].Cl.N1C=CC=CC=1>C(OCCO)C>[CH3:1][O:2][C:3](=[O:19])[CH2:4][CH2:5][CH2:6][C:7]1[S:18][C:10]2=[N:11][CH:12]=[C:13]([C:16]#[N:17])[C:14]([NH:25][C:24]3[CH:26]=[C:27]([O:31][CH3:32])[C:28]([O:29][CH3:30])=[C:22]([O:21][CH3:20])[CH:23]=3)=[C:9]2[CH:8]=1

Participants

5

Reactant 3

HCID 322853,4,5-TrimethoxyanilineHCID 10176127Pyridinium chlorideHCID 69233946HCID 69233946, compound

Product 1

HCID 10003428HCID 10003428, compoundYield 70.2%

Reagents, catalysts & solvents 1

HCID 8076Glycol monoethyl etherSolvent

Procedure

A mixture of 4-(4-chloro-5-cyano-thieno[2,3-b]pyridin-2-yl)-butyric acid methyl ester (60 mg, 0.20 mmol), 3,4,5-trimethoxyaniline (92 mg, 0.50 mmol), and pyridine hydrochloride (10 mg, 0.09 mmol) in 10 mL of 2-ethoxyethanol is heated at reflux for 24 hours. The solution is cooled and the solvent is evaporated. The residue is purified by flash column chromatography eluting with 1:1 ethyl acetate:hexane to provide 62 mg of 4-[5-cyano-4-(3,4,5-trimethoxy-phenylamino)-thieno[2,3-b]pyridin-2-yl]-butyric acid methyl ester as a tan solid, mp 101-103° C.; 1H NMR (DMSO-d6) δ 1.94 (quintet, J=7 Hz, 2H), 2.41 (t, J=7 Hz, 2H), 2.88 (t, J=7 Hz, 2H), 3.60 (s, 3H), 3.67 (s, 3H), 3.75 (s, 6H), 6.60 (s, 2H), 7.28 (s, 1H), 8.40 (s, 1H), 9.62 (s, 1H); MS 442.1 (M+H)+.

Workup

  1. temperatureis heated
  2. temperatureat reflux for 24 hours
  3. temperatureThe solution is cooled
  4. customthe solvent is evaporated
  5. customThe residue is purified by flash column chromatography
  6. washeluting with 1:1 ethyl acetate

Sources & evidence

ORD record
ord-1b1c47d846af48eebbfe4c9def57d4fe
Source dataset
uspto-grants-2006_01
Patent number
US06987116B2

Reaction notes

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