M-Phenylenediamine → N-(3-Aminophenyl)-3-[(quinolin-4-ylmethyl)amino]thiophene-2-carboxamide

HRID 2116591Notes

Reaction equation

HRID 2116591 reaction equation
[C:1]1([NH2:8])[CH:6]=[CH:5][CH:4]=[C:3]([NH2:7])[CH:2]=1.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>C1(C)C=CC=CC=1>[NH2:7][C:3]1[CH:2]=[C:1]([NH:8][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:5][CH:4]=1

Participants

5

Reactant 3

HCID 7935M-PhenylenediamineHCID 16682925TrimethylaluminumHCID 59734303Methyl 3-[(quinolin-4-ylmethyl)amino]thiophene-2-carboxylate

Product 1

HCID 59814810N-(3-Aminophenyl)-3-[(quinolin-4-ylmethyl)amino]thiophene-2-carboxamide

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 1,3 phenylenediamine (5.43 g, 50.3 mmol) in anhydrous toluene (100 mL) was added AlMe3 (2M in toluene, 7.5 mL, 15.1 mmol) and the solution was stirred at rt overnight. Methyl 3-[(quinolin-4-ylmethyl)amino]thiophene-2-carboxylate (3 g, 10.05 mmol) was added and the mixture was stirred at 130° C. for 3 h. The reaction mixture was cooled to rt and the toluene was decanted. To the remaining residue, 50 mL of 2N NaOH and 100 mL of CH2Cl2 were added and the solution stirred for 30 min. The CH2Cl2 layer was separated and the aqueous layer was extracted with CH2Cl2 (3×50 mL). The toluene and CH2Cl2 layers were combined, washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Purification by silica gel chromatography (50% hexanes:ethyl acetate→100% ethyl acetate) followed by trituration of the solid with CH2Cl2 yielded pure N-(3-aminophenyl)-3-[(quinolin-4-ylmethyl)amino]thiophene-2-carboxamide as a tan powder. MS (ES): m/z 374.86 (100) [MH+]; 1H NMR (DMSO-d6, 400 MHz): δ 4.98-4.50 (m, 2H), 5.04 (d, J=5.6 Hz, 2H), 6.25 (d, J=7.2 Hz, 1H), 6.72 (d, J=8.0 Hz, 1H), 6.79 (d, J=5.6 Hz, 1H), 6.89 (t, J=8.0 Hz, 1H), 6.96-6.97 (m, 1H), 7.39 (d, J=4.4 Hz, 1H), 7.55 (d, J=5.6 Hz, 1H), 7.66 (t, J=7.2 Hz, 1H), 7.78 (t, J=6.8 Hz, 1H), 8.00-8.05 (m, 2H), 8.21 (d, J=8.0 Hz, 1H), 8.82 (d, J=4.4 Hz, 1H), 9.08 (s, 1H).

Workup

  1. stirringthe mixture was stirred at 130° C. for 3 h
  2. temperatureThe reaction mixture was cooled to rt
  3. customthe toluene was decanted
  4. additionTo the remaining residue, 50 mL of 2N NaOH and 100 mL of CH2Cl2 were added
  5. stirringthe solution stirred for 30 min
  6. customThe CH2Cl2 layer was separated
  7. extractionthe aqueous layer was extracted with CH2Cl2 (3×50 mL)
  8. washwashed with brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customPurification by silica gel chromatography (50% hexanes:ethyl acetate→100% ethyl acetate)

Sources & evidence

ORD record
ord-9d22cac50e62493b965f29608d1c6064
Source dataset
uspto-grants-2008_10
Patent number
US07439256B2

Reaction notes

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