N,N-dimethyl-3-azabicyclo[3.2.1]octan-8-amine

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

Procedure: The 6-(7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)nicotinic acid was combined with N,N-dimethyl-3-azabicyclo[3.2.1]octan-8-amine following amide formation method 3 which gave 7-cyclopentyl-2-(5-(8-(dimethylamino)-3-azabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-ylamino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (12 mg) 14% yield. 1H NMR (400 MHz, CDCl3) δ ppm 8.82 (s, 1H) 8.76 (s, 1H) 8.55 (d, J=9.60 Hz, 1H) 8.44 (d, J=2.02 Hz, 1H) 7.78 (dd, J=8.59, 2.02 Hz, 1H) 6.48 (s, 1H) 4.87-4.73 (m, 1H) 4.31 (br. s., 1H) 3.75 (br. s., 1H) 3.35 (m, 2H) 3.16 (s, 6H) 2.68-2.51 (m, 2H) 2.30 (s, 7H) 2.16-1.97 (m, 6H) 1.86-1.66 (m, 6H). HR-MS (m/z MH+) 531.32 RT 2.67 min

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

Procedure: 3-benzyl-N,N-dimethyl-3-azabicyclo[3.2.1]octan-8-amine (80 mg, 0.45 mmol) was dissolved in MeOH (10 ml) and the atmosphere was replaced with N2 (3×). 10% Pd/C (cat.) was added and the atmosphere was replaced with H2 (3×). The resulting reaction mixture was stirred at RT at balloon pressure overnight. When TLC showed no more UV active spot the Pd/C was filtered off (always keeping wet with MeOH) and the filtrate was concentrated which gave N,N-dimethyl-3-azabicyclo[3.2.1]octan-8-amine (44 mg) in 87% yield. 1H NMR (400 MHz, MeOD) δ ppm 3.45 (d, J=12.13 Hz, 2H) 2.88 (dd, J=12.38, 2.78 Hz, 2H) 2.35 (d, J=2.02 Hz, 2H) 2.31-2.23 (m, 6H) 2.11 (t, J=4.80 Hz, 1H) 2.06-1.92 (m, 2H) 1.89-1.79 (m, 2H) The resulting reaction mixture was filtered off ( was concentrated which

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

Procedure: 3-benzyl-N,N-dimethyl-3-azabicyclo[3.2.1]octan-8-amine (80 mg, 0.45 mmol) was dissolved in MeOH (10 ml) and the atmosphere was replaced with N2 (3×). 10% Pd/C (cat.) was added and the atmosphere was replaced with H2 (3×). The resulting reaction mixture was stirred at RT at balloon pressure overnight. When TLC showed no more UV active spot the Pd/C was filtered off (always keeping wet with MeOH) and the filtrate was concentrated which gave N,N-dimethyl-3-azabicyclo[3.2.1]octan-8-amine (44 mg) in 87% yield. 1H NMR (400 MHz, MeOD) δ ppm 3.45 (d, J=12.13 Hz, 2H) 2.88 (dd, J=12.38, 2.78 Hz, 2H) 2.35 (d, J=2.02 Hz, 2H) 2.31-2.23 (m, 6H) 2.11 (t, J=4.80 Hz, 1H) 2.06-1.92 (m, 2H) 1.89-1.79 (m, 2H) The resulting reaction mixture was filtered off ( was concentrated which

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

Procedure: The 6-(7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)nicotinic acid was combined with N,N-dimethyl-3-azabicyclo[3.2.1]octan-8-amine following amide formation method 3 which gave 7-cyclopentyl-2-(5-(8-(dimethylamino)-3-azabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-ylamino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (12 mg) 14% yield. 1H NMR (400 MHz, CDCl3) δ ppm 8.82 (s, 1H) 8.76 (s, 1H) 8.55 (d, J=9.60 Hz, 1H) 8.44 (d, J=2.02 Hz, 1H) 7.78 (dd, J=8.59, 2.02 Hz, 1H) 6.48 (s, 1H) 4.87-4.73 (m, 1H) 4.31 (br. s., 1H) 3.75 (br. s., 1H) 3.35 (m, 2H) 3.16 (s, 6H) 2.68-2.51 (m, 2H) 2.30 (s, 7H) 2.16-1.97 (m, 6H) 1.86-1.66 (m, 6H). HR-MS (m/z MH+) 531.32 RT 2.67 min

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

Procedure: 3-benzyl-N,N-dimethyl-3-azabicyclo[3.2.1]octan-8-amine (80 mg, 0.45 mmol) was dissolved in MeOH (10 ml) and the atmosphere was replaced with N2 (3×). 10% Pd/C (cat.) was added and the atmosphere was replaced with H2 (3×). The resulting reaction mixture was stirred at RT at balloon pressure overnight. When TLC showed no more UV active spot the Pd/C was filtered off (always keeping wet with MeOH) and the filtrate was concentrated which gave N,N-dimethyl-3-azabicyclo[3.2.1]octan-8-amine (44 mg) in 87% yield. 1H NMR (400 MHz, MeOD) δ ppm 3.45 (d, J=12.13 Hz, 2H) 2.88 (dd, J=12.38, 2.78 Hz, 2H) 2.35 (d, J=2.02 Hz, 2H) 2.31-2.23 (m, 6H) 2.11 (t, J=4.80 Hz, 1H) 2.06-1.92 (m, 2H) 1.89-1.79 (m, 2H) The resulting reaction mixture was filtered off ( was concentrated which

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

Procedure: The 6-(7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)nicotinic acid was combined with N,N-dimethyl-3-azabicyclo[3.2.1]octan-8-amine following amide formation method 3 which gave 7-cyclopentyl-2-(5-(8-(dimethylamino)-3-azabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-ylamino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (12 mg) 14% yield. 1H NMR (400 MHz, CDCl3) δ ppm 8.82 (s, 1H) 8.76 (s, 1H) 8.55 (d, J=9.60 Hz, 1H) 8.44 (d, J=2.02 Hz, 1H) 7.78 (dd, J=8.59, 2.02 Hz, 1H) 6.48 (s, 1H) 4.87-4.73 (m, 1H) 4.31 (br. s., 1H) 3.75 (br. s., 1H) 3.35 (m, 2H) 3.16 (s, 6H) 2.68-2.51 (m, 2H) 2.30 (s, 7H) 2.16-1.97 (m, 6H) 1.86-1.66 (m, 6H). HR-MS (m/z MH+) 531.32 RT 2.67 min

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

Procedure: 3-benzyl-N,N-dimethyl-3-azabicyclo[3.2.1]octan-8-amine (80 mg, 0.45 mmol) was dissolved in MeOH (10 ml) and the atmosphere was replaced with N2 (3×). 10% Pd/C (cat.) was added and the atmosphere was replaced with H2 (3×). The resulting reaction mixture was stirred at RT at balloon pressure overnight. When TLC showed no more UV active spot the Pd/C was filtered off (always keeping wet with MeOH) and the filtrate was concentrated which gave N,N-dimethyl-3-azabicyclo[3.2.1]octan-8-amine (44 mg) in 87% yield. 1H NMR (400 MHz, MeOD) δ ppm 3.45 (d, J=12.13 Hz, 2H) 2.88 (dd, J=12.38, 2.78 Hz, 2H) 2.35 (d, J=2.02 Hz, 2H) 2.31-2.23 (m, 6H) 2.11 (t, J=4.80 Hz, 1H) 2.06-1.92 (m, 2H) 1.89-1.79 (m, 2H) The resulting reaction mixture was filtered off ( was concentrated which