2-Chloromethyloxazole

To a solution of 2-(hydroxymethyl)oxazole (450 mg, 4.5 mmol) in DCM (25 mL) at 0°C was added dropwise thionyl chloride (3.25 mL, 45 mmol). After stirring for 1 h, water (50 mL) and EtOAc (60 mL) were added. The phases were separated and the organic extracts Concentrated in vacuo to provide the title compound as a white solid (200 mg, 1 .7 mmol, 37percent).General procedure: To a solution of 4-chloro-lH-pyrrolo-[3, 2-c]-pyridine [60290-21-3] (2.0 g, 13.1 mmol) dissolved in DMF (30.5 mL, 0.944 g/mL, 393.2 mmol) at 0C was added portionwise sodium hydride (1.1 g, 28.8 mmol). The reaction mixture was allowed to reach rt and stirred 45 min, after which it was re-cooled to 0C and l-bromobutane (2.1 mL, 1.27 g/mL, 19.7 mmol) was added dropwise. The mixture was then allowed to reach rt and stirred overnight. NaHC03 sat solution was added and the aqueous phase was extracted with EtOAc. The combined organic extracts were washed with water and brine, then dried over MgS04 and concentrated in vacuo. The crude residue was purified by column chromatography (silica gel; gradient Heptane/EtOAc from 100/0 to 50 /50) to yield 1-1 (2.7 g, 98.7%) as a yellow liquid6-bromopyridazine-1(2H)-one (0.80 g, 3.55 mmol), A solution of cesium carbonate (2.89 g, 8.86 mmol) and A mixture of To a solution of 5-(1 H-benzo[d]imidazol-2-yl)-N, N-diethylpyridin-2-amine (400 mg, 1 .502 mmol) in THF (20 mL) was added NaH (60%, 240 mg, 6.01 mmol), and the resulting mixture was stirred at room temperature for 30 minutes. To a solution of methyl 6-( 1 -(( 1H-pyrazol-4-yl)sulfonyl)piperidin-4-yl)-4-(2-chloro-3 , 4-difluorophenyl)-2-(thiazol-2-yl)- 1 , 4-dihydropyrimidine-5 -carboxylate 324 (90 mg, 0.154 mmol) in N, N-dimethylformamide (3 mL) was added To a solution of methyl 6-( 1 -(( 1H-pyrazol-4-yl)sulfonyl)piperidin-4-yl)-4-(2-ch loro-3 -fluorophenyl)-2-(thiazol-2-yl)- 1 , 4-dihydropyrimidine-5 -carboxylate 1 58A (80.0 mg, 0.142 mmol) in N, N-dimethylformamide (2 mL) was added potassium carbonate(39.0 mg, 0.284 mmol) and sodium iodide (21.0 mg, 0.142 mmol) at room temperature. After stirred at room temperature for 5 minutes, Aroom temperature mixture of tert-butyl 4-(5 -(3 -cyano-6-hydroxypyrazolo[ 1, 5 -a]pyridin-4- yl)pyridin-2-yl)piperazine-1-carboxylate (Intermediate P3; 77.5 mg, 0.184 mmol) and K2C03(s) (50.9 mg, 0.369 mmol) in DMF (1.84 mL) was treated with General procedure: A solution of 6-hydroxy-4-(6-(6-((6-methoxypyridin-3 -yl)methyl)-3 , 6- diazabicyclo[3. 1.1 ]heptan-3 -yl)pyridin-3 -yl)pyrazolo[ 1, 5 -a]pyridine-3 -carbonitrile (Intermediate P71; 25 mg, 0.055 1 mmol) in DMA (551 tL) was treated sequentially with C52CO3(s) (53.9 mg, 0.165 mmol) and (ls, 3s)-3-(bromomethyl)cyclobutan-1-ol, cis (10.9 mg, 0.0662 mmol) then stirred overnight at 100 C. After cooling to ambient temperature, the reaction mixture was purified directly by C18 reverse phase chromatography (using 5-95% ACN in water with 0.1% TFA as the gradient eluent) to afford the TFA salt of the title compound. The TFA salt was dissolved in MeOH (1 mL), passed through a P1-HCO3 resin, and concentrated in vacuo to cleanly afford the title compound (6.2 mg, 21% yield). MS (apci) m/z = 538.3 (M+H).A mixture of the methyl 5-aminopicolinate (456 mg, 3 mmol),

Molecular Weight:117.53
XLogP3:0.8
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:116.9981414
Monoisotopic Mass:116.9981414
Topological Polar Surface Area:26
Heavy Atom Count:7
Complexity:59.7
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes