(2R,4S)-1-tert-Butyl 2-methyl 4-aminopyrrolidine-1,2-dicarboxylate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared using methods analogous to those described in Synthesis 80-A, 30-A, 76-B and 89-B, replacing 2-amino-5-methoxybenzoic acid with 2-amino-4-methoxybenzoic acid in Synthesis 80-A, replacing (S)-(−)-1-boc-3-aminopyrrolidine with (2R,4S)-4-aminopyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester in Synthesis 30-A, replacing 2-hydroxyphenylboronic acid with 5-fluoro-2-hydroxyphenylboronic acid in Synthesis 76-B (using the crude Boc-protected amine in Synthesis 89-B), and replacing (2R,4S)-1-tert-butyl 2-methyl 4-(2-(5-fluoro-2-hydroxyphenyl)quinazolin-4-ylamino)pyrrolidine-1,2-dicarboxylate with (2R,4S)-1-tert-butyl 2-methyl 4-(2-(5-fluoro-2-hydroxyphenyl)-7-methoxyquinazolin-4-ylamino)pyrrolidine-1,2-dicarboxylate in Synthesis 89-B.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Chloro-2-(2-methoxyphenyl)quinazoline (0.463 g, 1.709 mmol), (2R,4S)-4-aminopyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (0.480 g, 1.709 mmol) and triethylamine (0.715 mL, 5.127 mmol) in dioxane (9 mL) were heated at reflux for 3 days. The mixture was cooled, diluted with dichloromethane (50 mL), and washed with water (50 mL). The organic extracts were dried (MgSO4) and concentrated. Purification by silica gel chromatography (10% methanol in dichloromethane) gave the title compound as a solid (0.423 g, 52%). at reflux for 3 days The mixture was cooled washed with water (50 mL) The organic extracts were dried (MgSO4) concentrated Purification by silica gel chromatography (10% methanol in dichloromethane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of trans-4-azido-N-tert-butoxycarbonyl-D-proline methyl ester (C, 1.04 g) and 10% palladium on activated carbon (500 mg) in methanol (30 mL) was stirred at room temperature for 1.5 hr under hydrogen. The catalysts were removed by filtration and washed with methanol. The combined organic layers were evaporated in vacuo to give the title compound (0.90 g) as a colorless oil. The catalysts were removed by filtration washed with methanol The combined organic layers were evaporated in vacuo