5-methylsulfanyl-3,4-dihydro-2H-pyrrole

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

Procedure: A solution of 4-methyl-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-amine, (775 mg, 2.7 mmol) and 5-(methylthio)-3,4-dihydro-2H-pyrrole (345 mg) in i-PrOH (14 mL) was heated at 105° C. for 3 days. The refluxed mixture was then cooled to room temperature and concentrated. Flash column chromatography (4-6% 7N NH3 in MeOH/DCM) yielded N-(3,4-dihydro-2H-pyrrol-5-yl)-4-methyl-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-amine, (180 mg) 1H NMR (300 MHZ, CD3OD) δ: 8.10 (d, J=7.6 Hz, 2H), 7.89 (s, 1H), 7.75 (d, J=4.1 Hz, 1H), 7.63 (s, 1H), 7.54 (d, J=8.2 Hz, 2H), 6.77 (d, J=4.1 Hz, 1H), 2.63 (s, 2H), 2.09 (t, J=7.5 Hz, 3H). concentrated

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

Procedure: A solution of 4-methyl-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-amine, (775 mg, 2.7 mmol) and 5-(methylthio)-3,4-dihydro-2H-pyrrole (345 mg) in i-PrOH (14 mL) was heated at 105° C. for 3 days. The refluxed mixture was then cooled to room temperature and concentrated. Flash column chromatography (4-6% 7N NH3 in MeOH/DCM) yielded N-(3,4-dihydro-2H-pyrrol-5-yl)-4-methyl-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-amine, (180 mg) 1H NMR (300 MHZ, CD3OD) δ: 8.10 (d, J=7.6 Hz, 2H), 7.89 (s, 1H), 7.75 (d, J=4.1 Hz, 1H), 7.63 (s, 1H), 7.54 (d, J=8.2 Hz, 2H), 6.77 (d, J=4.1 Hz, 1H), 2.63 (s, 2H), 2.09 (t, J=7.5 Hz, 3H). concentrated

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

Procedure: To a solution of diisopropylamine (6.32 g, 62.52 mmol) in THF (100 mL) was dropwise added n-BuLi (2.89 M, 21.63 mL, 62.52 mmol) at −78° C. under nitrogen. Once all the n-BuLi was added, the temperature was adjusted to −5° C., and the reaction mixture was stirred for 30 min. Then a solution of 2-methyl-3,4,5,6-tetrahydropyridine (3.76 g, 38.70 mmol) in THF (15 mL) was added dropwise to the reaction mixture at −5° C., and then stirred. After 30 min, 2-methylthio-1-pyrroline (3.43 g, 29.77 mmol) was added dropwise over 30 min at −78° C. The reaction mixture was stirred as the temperature was allowed to gradually rise to room temperature, and was continuously stirred at room temperature overnight. THF solvent was removed under reduced pressure, then 30 mL of methanol was added dropwise to the residue. After removing all of the volatile solvent, pentane (2×50 mL) was added to the residue, and the mixture was filtered. Concentration of the filtrate under reduced pressure, followed by vacuum distillation (75° C. at 185 mTorr) delivered 4.1 g of product (84%). 1H NMR (CD2Cl2, 500 MHz): δ 9.64 (s, br, 1H), 4.48 (s, 1H), 3.78 (t, 2H, J=7.3 Hz), 3.27 (t, 2H, J=6.1 Hz), 2.45 (m, 2H), 2.33 (t, 2H, J=6.2 Hz), 1.73 (m, 4H), 1.67 (m, 2H). 13CNMR (CD2Cl2, 125 MHz): δ 173.6, 155.8, 86.5, 60.0, 41.7, 37.9, 29.5, 23.8, 22.7, 21.3. at −78° C. was adjusted to −5° C. stirred After 30 min The reaction mixture was stirred as the temperature to gradually rise to room temperature was continuously stirred at room temperature overnight THF solvent was removed under reduced pressure 30 mL of methanol was added dropwise to the residue After removing all of the volatile solvent, pentane (2×50 mL) was added to the residue the mixture was filtered Concentration of the filtrate under reduced pressure, followed by vacuum distillation (75° C. at 185 mTorr)

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

Procedure: To a solution of diisopropylamine (11.1 g, 109.7 mmol) in THF (200 mL) was dropwise added n-BuLi (2.89 M, 37.97 mL, 109.7 mmol) at −78° C. under nitrogen. Once all the n-BuLi was added, the temperature was adjusted to −5° C., and the reaction mixture was stirred for 30 min. Then a solution of 2-methyl-1-pyrroline (5.65 g, 67.9 mmol) in THF (15 mL) was added dropwise to the reaction mixture at −5° C., and then stirred. After 30 min, 2-methylthio-1-pyrroline (6.02 g, 52.3 mmol) was added dropwise over 30 min at −78° C. The reaction mixture was stirred as the temperature was allowed to gradually rise to room temperature, and was continuously stirred at room temperature overnight. THF solvent was removed under reduced pressure, then 50 mL of methanol was added dropwise to the residue. After removing all of the volatile solvent, pentane (2×100 mL) was added to the residue, and the mixture was filtered. Concentration of the filtrate under reduced pressure, followed by vacuum distillation (65° C. at 110 mTorr), delivered 6.29 of product (79%). 1H NMR (CD2Cl2, 500 MHz): δ 7.89 (s, br, 1H), 4.65 (s, 1H), 3.64 (t, 2H, J=7.2 Hz), 2.51 (t, 2H, J=8.0 Hz), 1.85 (m, 2H). 13C NMR (CD2Cl2, 125 MHz): δ 167.0, 81.7, 53.7, 34.8, 23.2. at −78° C. was adjusted to −5° C. stirred After 30 min The reaction mixture was stirred as the temperature to gradually rise to room temperature was continuously stirred at room temperature overnight THF solvent was removed under reduced pressure 50 mL of methanol was added dropwise to the residue After removing all of the volatile solvent, pentane (2×100 mL) was added to the residue the mixture was filtered Concentration of the filtrate under reduced pressure, followed by vacuum distillation (65° C. at 110 mTorr)

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

Procedure: A solution of 4-methyl-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-amine, (775 mg, 2.7 mmol) and 5-(methylthio)-3,4-dihydro-2H-pyrrole (345 mg) in i-PrOH (14 mL) was heated at 105° C. for 3 days. The refluxed mixture was then cooled to room temperature and concentrated. Flash column chromatography (4-6% 7N NH3 in MeOH/DCM) yielded N-(3,4-dihydro-2H-pyrrol-5-yl)-4-methyl-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-amine, (180 mg) 1H NMR (300 MHZ, CD3OD) δ: 8.10 (d, J=7.6 Hz, 2H), 7.89 (s, 1H), 7.75 (d, J=4.1 Hz, 1H), 7.63 (s, 1H), 7.54 (d, J=8.2 Hz, 2H), 6.77 (d, J=4.1 Hz, 1H), 2.63 (s, 2H), 2.09 (t, J=7.5 Hz, 3H). concentrated