3-Iodoaniline → 3-[(Quinolin-4-ylmethyl)amino]thiophene-2-carboxylic acid (3-iodophenyl)amide

HRID 1171897Notes

Reaction equation

HRID 1171897 reaction equation
[I:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].C[Al](C)C.[N:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]([CH2:23][NH:24][C:25]2[CH:29]=[CH:28][S:27][C:26]=2[C:30](OC)=[O:31])=[CH:15][CH:14]=1.[OH-].[Na+]>C1(C)C=CC=CC=1>[I:1][C:2]1[CH:3]=[C:4]([NH:5][C:30]([C:26]2[S:27][CH:28]=[CH:29][C:25]=2[NH:24][CH2:23][C:16]2[C:17]3[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=3)[N:13]=[CH:14][CH:15]=2)=[O:31])[CH:6]=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 122713-IodoanilineHCID 14798Sodium HydroxideHCID 16682925TrimethylaluminumHCID 59734303Methyl 3-[(quinolin-4-ylmethyl)amino]thiophene-2-carboxylate

Product 1

HCID 586460363-[(Quinolin-4-ylmethyl)amino]thiophene-2-carboxylic acid (3-iodophenyl)amide

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To a stirred suspension of 3-iodoaniline (1.27 mL, 1 mmol) in anhydrous toluene (100 mL) in a pre-dried flask under N2 atmosphere was added trimethylaluminium (6.1 mL of a 2M solution in toluene, 12.0 mmol), and the resulting solution left to stir at rt overnight. Methyl 3-[(quinolin-4-ylmethyl)amino]thiophene-2-carboxylate (3.0 g, 10 mmol) was then added and the mixture heated at reflux for 5 h. Upon cooling to rt, 100 mL of 2M NaOH was added and the mixture was stirred for 30 min. The solution was then partitioned over CH2Cl2 and the aqueous phase was extracted with CH2Cl2 (3×100 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. The resulting brown solid was treated with MeOH, sonicated for 2 min, and filtered. The solid was washed with MeOH to provide 3-[(quinolin-4-ylmethyl)amino]thiophene-2-carboxylic acid (3-iodophenyl)amide as a brown powder. MS (ES): m/z 485.8 [M+1]. 1H NMR (DMSO-d6, 400 MHz): δ5.06 (d, J=5.4 Hz, 2H), 6.77 (d, J=5.6 Hz, 1H), 7.08 (t, J=8.0 Hz, 1H), 7.37 (d, J=6.0 Hz, 2H), 7.60 (d, J=5.6 Hz, 1H), 7.66-7.69 (m, 2H), 7.78 (t, J=7.6 Hz, 1H), 8.04 (d, J=8.4 Hz, 1H), 8.04-8.10 (m, 1H), 8.19 (s, 1H), 8.22 (d, J=8.8 Hz, 1H), 8.82 (d, J=4.4 Hz, 1H), 9.47 (s, 1H).

Workup

  1. waitleft
  2. temperaturethe mixture heated
  3. temperatureat reflux for 5 h
  4. temperatureUpon cooling to rt
  5. stirringthe mixture was stirred for 30 min
  6. customThe solution was then partitioned over CH2Cl2
  7. extractionthe aqueous phase was extracted with CH2Cl2 (3×100 mL)
  8. dry with materialThe combined organic extracts were dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. additionThe resulting brown solid was treated with MeOH
  12. customsonicated for 2 min
  13. filtrationfiltered
  14. washThe solid was washed with MeOH

Sources & evidence

ORD record
ord-94e0945f6ada4b0f98ccc592749216b8
Source dataset
uspto-grants-2010_11
Patent number
US07829717B2

Reaction notes

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