1,3,5-Trimethyl-1H-pyrazole-4-carboxaldehyde

Light yellow powder

In a lOO-mL round bottom flask purged and maintained with an inert atmosphere of nitrogen, to a solution of tert-butyl N- [2-(2, 3-diaminopyridin-4-yl)-6, 7, 8, 9-tetrahydro-5H-benzo[7]annulen-5-yl]carbamate (1.3 g, 3.18 mmol, 1.00 equiv) and l, 3, 5-trimethyl-lH-pyrazole-4-carbaldehyde (488 mg, 3.36 mmol, 1.06 equiv) in N, N-dimethylformamide (30 mL) was added 4-methylbenzene-l -sulfonic acid (61 mg, 0.35 mmol, 0.11 equiv) at room temperature. The resulting mixture was stirred for 4 days at 100 C. After the reaction was done, the reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel column eluting with methanol in DCM (1% to 10% gradient) to afford tert-butyl N-[2-[2-(trimethyl-lH-pyrazol-4-yl)-3H-imidazo[4, 5-b]pyridin-7- yl]-6, 7, 8, 9-tetrahydro-5H-benzo[7]annulen-5-yl]carbamate as a brown solid (0.6 g, 39%). MS: m/z = 487.4 [M+Hf.General procedure: Sodium triacetoxyborohydride (46.3 mg, 0.218 mmol) was added toa mixture of 10c (65 mg, 0.146 mmol) and tetrahydropyran-4-carbaldehyde(18.3 mg, 0.160 mmol) in 1, 2-dichloroethane (1.30 mL). The mixture was stirred at room temperature for 2 h, sat.NaHCO3 aqueoussolution was added, and the mixture was extracted with CHCl3. The organic layer was washed with brine, dried with Na2SO4, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (CHCl3/MeOH) to give the desired compound as a white solid (41.0 mg, 52%). 1H NMR (DMSO-d6) delta1.00-1.29 (3H, m), 1.44-1.60 (3H, m), 1.64-1.85 (3H, m), 1.95-2.17(5H, m), 2.62-2.71 (1H, m), 2.78-2.88 (1H, m), 3.08 (3H, s), 3.15-3.29(2H, m), 3.70-3.83 (2H, m), 4.01 (3H, s), 4.05 (3H, s), 4.27-4.37 (2H, m), 7.26 (1H, s), 8.11 (1H, s), 8.43 (1H, d, J=2.3 Hz), 8.85 (1H, d, J=2.3 Hz), 9.37 (1H, s); ESI-MS m/z 545.3 [(M+H)+]; HRMS(ESI) m/z calcd for C26H37N6O5S [(M+H)+]: 545.2541, found: 545.2537General procedure: Into a vessel of the microwave reactor, equipped with a stirring bar, was charged 0.22 g (1 mmol) of pyrazolecarbaldehyde 1a, 0.094 g (1.06 mmol, 5% excess) of 2-amino-2-methylpropan-1-ol 2, 2 mL of anhydrous C6H6, and the reactor was filled with argon. The reaction mixture in the presence of molecular sieves 4 A was heated for 2 h at microwave irradiation at 150C, and then the solvent was removed at a reduced pressure. The crude reaction product was washed with hexane (2 × 2 mL), cooled to 0C, dried in a vacuum over P2O5. Yield 0.289 g (99%) of a mixture of azomethine 3a and oxazolidine 4a, 60 : 40, light-yellow crystals.

Molecular Weight:138.17
XLogP3:0.5
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:138.079312947
Monoisotopic Mass:138.079312947
Topological Polar Surface Area:34.9
Heavy Atom Count:10
Complexity:138
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes