2-(2-Pyridinyloxy)ethanamine

Add sodium hydride (60percent in mineral oil, 6.63 g, 166 mmol) to a solution of 2- hydroxyethylamine (10.0 mL, 166 mmol) in dioxane (150 mL) at room temperature under nitrogen. After stirring for 10 minutes at room temperature, add 2-chloropyridine (15.6 mL, 166 mmol) and heat the reaction mixture to reflux. After stirring at reflux for 14 hours, cool the reaction mixture to room temperature and dilute with water (100 mL) and methylene chloride (200 mL). Extract the aqueous layer with methylene chloride (2 x 100 mL). Wash the combined organic phase with brine (200 mL), dry over magnesium sulfate, filter, and concentrate to an orange oil. Flash chromatography on silica gel eluting with 50percent of a (80: 18: 2 CHCl3/MeOH/concentrated NH40H) solution in methylene chloride affords 2-phenoxy-ethylamine as a yellow oil (17.9 g, 78percent). 1H NMR (CDC13) 8 8.09-8. 15 (m, 1H), 7.53-7. 56 (m, 1H), 6.80-6. 85 (m, 1H), 6.70-6. 75 (m, 1H), 4.27-4. 31 (m, 2H), 3.06-3. 10 (m, 2H); MS (ES): m/z 139 (M + H). Add 2- (pyridin-2-yloxy) ethylamine (500 mg, 3.62 mmol) to a solution of 2- THIOACETYL-ISOINDOLE-1, 3-dione (743 mg, 3.62 mmol) in CHCI3 (18 mL) at 0°C. After stirring for 15 minutes, concentrate the solution, redissolve in ethyl acetate (25 mL), filter, and concentrate again. Flash chromatography (SI02, 1: 1 EtOAc/Hex) gives N- (2- (pyridin-2-yloxy) ethyl) thioacetamide (350 mg, 49percent) as a beige/pink SOLID. H NMR (CDC13) 8 8.79 (br s, 1H), 8.10-8. 08 (m, 1H), 7. 58-7. 65 (m, 1H), 6.92-7. 00 (m, 1H), 6.76- 6.82 (m, 1H), 4.57-4. 65 (m, 2H), 3.98-4. 05 (m, 2H), 2.56 (s, 3H). Add N- (2- (pyridin-2-yloxy) ethyl) thioacetamide (50 mg, 0.25 mmol) and methyl TRIFLUOROMETHANESULFONATE (0.028 mL, 0.25 mmol) in methylene chloride (1.5 mL), and stir at room temperature. After 10 minutes, concentrate the solution to dryness. To this residue, add a solution of biphenyl-4-carboxylic acid (R)- (6-AMINO-2 (R)-HYDROXYINDAN-L- YL) amide (95 mg, 0.275 mmol) in pyridine (3 mL). Stir the resulting solution at room temperature for 18 hours and remove the pyridine under vacuum. Flash chromatography (SIO2, 1: 1 EtOAc/Hex to 80: 18: 2 CHC13/MEOH/CONCENTRATED NH40H) gives the title compound (21 mg, 17percent) as a white SOLID. H NMR (CDC13) 8 7.88-7. 95 (M, 2H), 7.65- XI. 74 (M, 2H), 7.60-7. 70 (M, 2H), 7.40-7. 53 (M, 3H), 7.24-7. 26 (M, 2H), 7.02-7. 99 (m, GO), 6. 626.70 (M, 1H), 5.35-5. 42 (M, 1H), 4.55-4. 62 (M, 1H), 3.78-3. 90 (M, 4H), 3.30- 3.43 (M, 1H), 2.92-3. 08 (M, 1H), 2.02 (s, 3H); MS (ES): m/z 507 (M+ H).To NaH (60percent in mineral oil, 2.5 mmol) in dioxane (10 ml) was added 2-hydroxyethylamine(2.5 mmol) and heated to reflux for 30 min. Reaction was cooled toRT, 2-chloropyridine wasadded and heated to 80 oc for 18 h. Reaction was cooled to RT and concentrated. Water was added and then the mixture was extracted with DCM (x3). Combined organics weredried over Na2S04, concentrated and purified by flash chromatography with 5-10percentMeOH:DCM. Yield= 211 mg (61 percent), pale yellow oil.1H NMR (500 MHz, CDCb) o ppm 8.08- 8.20 (m, 1 H) 7.51 - 7.62 (m, 1 H) 6.86 (dd, J=6.49, 5.72 Hz, 1 H) 6.75 (d, J=8.24 Hz, 1 H) 4.32 (t, J=5.34 Hz, 2 H) 3.07 (t, J=5.26 Hz, 2 H).Compound MC-101-013 (195 mg, 0.54 mmol, 1.0 eq.), MC-164B-2 (200 mg, 1.45 mmol, 2.7 eq.) and triethylamine (328 mg, 3.24, 6.0 eq.)Dissolved in tetrahydrofuran (20 mL). After a 40-degree reaction for 5 hours, LCMS detects the reaction, after the reaction, The residue obtained by concentrating the reaction mixture was purified by silica gel chromatography (ethyl acetate / petroleum ether = 1/5)Purified to give a pale yellow solid compoundMC-164B-15(195 mg, 80%).

Molecular Weight:138.17
XLogP3:0.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:138.079312947
Monoisotopic Mass:138.079312947
Topological Polar Surface Area:48.1
Heavy Atom Count:10
Complexity:87.7
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes