2-Chloro-3,5-dimethoxyaniline

Potassium hydroxide (10.7g, 192mmol) was added to a solution of /V-(2-Chloro-3, 5- dimethoxy-phenyl)-acetamide (intermediate 33) (8.8g, 38.3mmol) in EtOH (500ml_) and water (50ml_) and the reaction mixture heated to reflux for 18 hours. Upon cooling, water was added (ca 30ml_) and the EtOH removed in vacuum. The residue was then partitioned between water and diethyl ether. The organic layer was separated, dried (MgS0c. 2-chloro~3Step 3: Intermediate 4[00521j To a 125 mL sealed flask was added Intermediate 3 (1.90 g, 8.27 mmol) in EtOH(50 mL, 856 mmol) followed by potassium hydroxide (2.32 g, 41.4 mmol) in 10 mL of water.The reaction was allowed to stir at 95 °C for 16 h after which it was cooled and concentrated.The resultant oil was partitioned between water and EtOAc, the organic layer was dried overMg504, filtered and concentrated to provide 1.00 g of the title compound MS mlz: 188.1(M+H).Step 4: Synthesis of Intermediate 5 [00522j Into a sealed vessel was added Intermediate 4 (1.50 g, 8.00 mmol) in DMA (5 mL, 53.3 mmol), followed by DIPEA (820 tl, 8.80 mmol). The reaction mixture was allowed to stir for 10 mm. at ambient temperature, and 2, 4-dichloro-5-(iodomethyl)pyrimidine from (2.31 g, 8.00 mmol) was added. The reaction mixture was allowed to stir at 60 °C for 7.5 h, then 16 h at ambient temperature. The reaction mixture was concentrated and azeotroped several times with toluene. EtOAc was added and the organic layer washed with brine (3 x). The organic layers were dried with sodium sulfate, concentrated and purified by flash column chromatography (eluting with 5-25percent EtOAc in heptane) to give 1.75 g of the title compound MS mlz: 348.2 (M+H).

Molecular Weight:187.62
XLogP3:1.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:187.0400063
Monoisotopic Mass:187.0400063
Topological Polar Surface Area:44.5
Heavy Atom Count:12
Complexity:145
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes