[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]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).
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