(3-methyloxetan-3-yl)methanamine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a solution of {2-[5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-5-yl}acetic acid (150 mg) in N,N-dimethylformamide (5 mL) were added 1-hydroxybenzotriazole monohydrate (65 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (81 mg), and 1-(3-methyloxetan-3-yl)methanamine (57 mg), and the mixture was stirred at room temperature for 15 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The obtained crude product was subjected to basic silica gel column chromatography (ethyl acetate:hexane=0:100 to 100:0, volume ratio), and crystallized from acetonitrile. The obtained crystals were recrystallized from ethyl acetate and diethyl ether to give the title compound (106 mg, yield 61%) as white crystals. the mixture was extracted with ethyl acetate The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine dried over magnesium sulfate filtered concentrated under reduced pressure The obtained crude product crystallized from acetonitrile The obtained crystals were recrystallized from ethyl acetate and diethyl ether

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

Procedure: The title compound, white solid, MS: m/e=280.2 (M+H+), can be prepared in accordance with the general method of example 1, step 3 from 2-methanesulfonyl-5-phenylethynyl-pyrimidine (example 1, step 2) and (3-methyloxetan-3-yl)methanamine.

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

Procedure: In analogy to the procedure described in Example 47 b), 6-cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid (Example 1 b)) was reacted with (3-methyloxetan-3-yl)methanamine (CAN 153209-97-3) in the presence of TBTU and DIEA to give the title compound as a byproduct as colorless oil; MS (EI): m/e=368.5 [MH+].

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:115.01; pressure:0.00; stir:

Procedure: In a 5 MW vial, Pd2((dba)3 (7.23 mg, 7.90 µmol), 2,2'-bis(diphenylphosphanyl)-1,1'-binaphthalene (BINAP) (9.71 mg, 0.02 mmol), sodium 2-methylpropan-2-olate (174 mg, 1.81 mmol), (3-methyloxetan-3-yl)methanamine (126 mg, 1.25 mmol) and 2-bromo-3-chloropyridine (200 mg, 1.04 mmol) mixed in toluene (2 mL) to give a brown suspension. The mixture was degassed with N2 bubbling for 5 min, then the vial was capped and the reaction stirred at 115°C in an oil-bath for 1h then to rt for 2h. LC-MS: 61% product, 28% sm left. The reaction was cooled to rt and the solvent was evaporated. The residue was purified by automated flash chromatography on a 25g column. A gradient from 5% to 50% of EtOAc in heptane over 15CV was used as mobile phase. The product was collected using the wavelength 315 nm, relevant fractions pooled and evaporated to give 27 mg suryp. LC-MS: M+1=213 found. 1H-NMR: OK, traces of sm and solvents left. 1H NMR (400 MHz, CDCl3) d 1.37 (s, 3H), 3.70 (d, 2H), 4.42 (d, 2H), 4.58 (d, 2H), 5.25 (s, 1H), 6.53 (dd, 1H), 7.44 (dd, 1H), 8.00 (dd, 1H). Expected Number of Hs: 13 Assigned Hs: 13.

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Following General Procedure L for reductive amination, 9-methyl-2-(2-methyl-1H-benzo[d]imidazol-1-yl)-6-morpholino-9H-purine-8-carbaldehyde and (3-methyloxetan-3-yl)methanamine were reacted to give 259. [M+H]+ 463.6. were reacted

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

Procedure: The title compound, white solid, MS: m/e=280.2 (M+H+), can be prepared in accordance with the general method of example 1, step 3 from 2-methanesulfonyl-5-phenylethynyl-pyrimidine (example 1, step 2) and (3-methyloxetan-3-yl)methanamine.

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

Procedure: Following General Procedure L for reductive amination, 9-methyl-2-(2-methyl-1H-benzo[d]imidazol-1-yl)-6-morpholino-9H-purine-8-carbaldehyde and (3-methyloxetan-3-yl)methanamine were reacted to give 259. [M+H]+ 463.6. were reacted

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

Procedure: From (2S)-2-[{4-[(4-formylphenyl)ethynyl]benzoyl}(methyl)amino]-N,2-dimethyl-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (0.15 g) as obtained in Example 16-(1) and [(3-methyloxetan-3-yl)methyl]amine (63 mg), (2S)-N,2-dimethyl-2-[methyl(4-{[4-({[(3-methyloxetan-3-yl)methyl]amino}methyl)phenyl]ethynyl}benzoyl)amino]-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (yellow solid) was obtained (0.13 g, 73%) in the same manner as in Example 16-(2).