Hydrochloric Acid → 3-amino-N-(2,4,6-trimethyl-3-pyrrolidin-1-ylphenyl)thiophene-2-carboxamide

HRID 2105284Notes

Reaction equation

HRID 2105284 reaction equation
[CH3:1][C:2]1[C:8]([N:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)=[C:7]([CH3:14])[CH:6]=[C:5]([CH3:15])[C:3]=1[NH2:4].C[Al](C)C.[NH2:20][C:21]1[CH:25]=[CH:24][S:23][C:22]=1[C:26](OC)=[O:27].Cl>ClCCCl>[NH2:20][C:21]1[CH:25]=[CH:24][S:23][C:22]=1[C:26]([NH:4][C:3]1[C:5]([CH3:15])=[CH:6][C:7]([CH3:14])=[C:8]([N:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)[C:2]=1[CH3:1])=[O:27]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 89652Methyl 3-amino-2-thiophenecarboxylateHCID 107982512,4,6-Trimethyl-3-(pyrrolidin-1-yl)anilineHCID 16682925Trimethylaluminum

Product 1

HCID 865967603-amino-N-(2,4,6-trimethyl-3-pyrrolidin-1-ylphenyl)thiophene-2-carboxamideYield 32.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 2,4,6-trimethyl-3-pyrrolidin-1-yl-aniline, (1.5 g, 7.6 mmol) in anhydrous 1,2 dichloroethane (20 mL), chilled to 0° C. under N2, was added a solution of trimethylaluminum (2M in hexanes) (7.6 mL, 15.2 mmol). Upon completion of the addition, the ice bath was removed and the reaction was stirred for 30 min. at room temperature. Methyl 3-amino-2-thiophenecarboxylate (0.95 g, 0.8 equivalents.) was added in one portion to the flask, and the reaction mixture was refluxed for 18 hours. The reaction mixture was acidified with hydrochloric acid (2N) (2×50 mL) and washed with dichloromethane (2×50 mL). The combined aqueous layers were then adjusted basic using a saturated, aqueous solution of sodium bicarbonate and extracted with ethyl acetate (2×50 mL). The combined organic ethyl acetate extracts were dried with magnesium sulfate, filtered, and concentrated under reduced pressure to yield a brown oil. The material was further purified by silica gel chromatography using 5% ethyl acetate in hexanes as the mobile phase (gradient) to yield 3-amino-N-(2,4,6-trimethyl-3-pyrrolidin-1-ylphenyl)thiophene-2-carboxamide as a yellow foam (640 mg).

Workup

  1. additionUpon completion of the addition
  2. customthe ice bath was removed
  3. temperaturethe reaction mixture was refluxed for 18 hours
  4. washwashed with dichloromethane (2×50 mL)
  5. extractionextracted with ethyl acetate (2×50 mL)
  6. dry with materialThe combined organic ethyl acetate extracts were dried with magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto yield a brown oil
  10. customThe material was further purified by silica gel chromatography

Sources & evidence

ORD record
ord-2ba8d70feeaf43f5a6465919a7d02008
Source dataset
uspto-grants-2009_08
Patent number
US07579340B2

Reaction notes

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