2-methyl-1-morpholin-4-ylpropan-2-amine

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

Procedure: Prepared as described for (R)-10-(3-hydroxy-3-(5-methylisoxazol-3-yl)but-1-yn-1-yl)-N3-(tetrahydro-2H-pyran-4-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2,3-dicarboxamide replacing 4-aminotetrahydropyran with 2-methyl-1-morpholinopropan-2-amine. Off-white solid 20 mg, 12%). Prepared

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

Procedure: A mixture of {5-(4-fluorobenzyl)-3-[1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl]-1H-pyrazol-1-yl}acetic acid (1.0 g, 2.37 mmol), 1,1-dimethyl-2-morpholin-4-yl-ethylamine (0.375 g, 2.37 mmol), HATU (0.71 g, 2.85 mmol) and Et3N (0.71 g, 7.1 mol) in DMF (20 mL) was stirred at room temperature overnight. The mixture was concentrated in vacuo and the residue was treated with water (50 mL) and CH2Cl2 (50 mL). The aqueous layer was extracted with CH2Cl2 (2×20 mL). The combined organics were dried over Na2SO4 and evaporated to afford crude title compound (1.3 g, 92%) as yellow oil that was used without further purification in next step. The mixture was concentrated in vacuo the residue was treated with water (50 mL) and CH2Cl2 (50 mL) The aqueous layer was extracted with CH2Cl2 (2×20 mL) The combined organics were dried over Na2SO4 evaporated

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

Procedure: The title compound was prepared in a manner similar to that described in Method G using (1aR,5aR)-2-(6-bromopyridin-3-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid and 2-methyl-1-morpholinopropan-2-amine. LCMS m/z=460.4 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 0.46 (td, J=4.7, 3.4 Hz, 1H), 1.27 (td, J=7.8, 4.8 Hz, 1H), 1.48 (s, 6H), 2.32-2.37 (m, 1H), 2.63-2.67 (m, 1H), 2.77 (d, J=16.4 Hz, 1H), 2.90 (dd, J=16.4, 6.6 Hz, 1H), 3.14-3.94 (m, 10H), 7.70 (s, 1H), 7.86 (dd, J=8.7, 0.5 Hz, 1H), 8.24 (d, J=7.7 Hz, 1H), 8.97 (s, 1H), 9.39 (s, 1H).

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

Procedure: Prepared as described for (R)-10-(3-hydroxy-3-(5-methylisoxazol-3-yl)but-1-yn-1-yl)-N3-(tetrahydro-2H-pyran-4-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2,3-dicarboxamide replacing 4-aminotetrahydropyran with 2-methyl-1-morpholinopropan-2-amine. Off-white solid 20 mg, 12%). Prepared