2-Bromo-1,1-dimethoxypropane

A mixture of compound 2-bromofuranylpropionaldehyde dimethyl acetal (1.0 g, 4.74 mmol) and hydrochloric acid (1 M, 3 mL) was heated to 90C and stirred for 1 hour. The reaction solution was cooled to room temperature and then neutralized to pH of 7 with a solid of sodium bicarbonate. Then 2-amino-5-bromopyridine (360 mg, 2.08 mmol) and methanol (5 mL) were added successively, and the reaction solution was heated to 90C and stirred overnight. The reaction solution was evaporated under reduced pressure to remove the organic solvent, diluted with water (10 mL) and dichloromethane. The organic layer was seperated, washed with water, saturated brine, dried over anhydrous sodium sulfate and evaporated under reduced pressure to give a crude product, which was purified by silica gel column chromatography to give compound 31-a as a gray solid (250 mg, 57%). LC-MS (ESI): m/z = 210.9 [M+H]+.A mixture of 2-[N-methyl-4-(trifluoromethoxy)anilino]pyrimidin-5-ol (0.4 g), Potassium hydroxide (0.158 g) and 2-bromo-I, I-dimethoxy-propane (0.4 mL)in N, N-Dimethylacetamide (4 mL)was heated at 100 00 for 24 h.The mixture was cooled to ambient temperature and water (50 mL) was added and the mixture extracted with Ethyl acetate (2 X 30 mL). The combined organic layer was washed with a saturated solution of Sodium chloride and dried over anhydrous Sodium sulphate and evaporated under reduced pressure and the crude obtained was purified by Silica gel flashcolumn chromatography using a gradient of Ethyl acetate/Hepatane to obtain the title compound(0.1 g, 18 %). LCMS: Rt: 2.144 min; MS: mz = 388.4 (M+1) 1H NMR (300 MHz, Chloroform-d) 68.14 (5, 2H), 7.36 (5, 3H), 7.25 (5, 2H), 7.16 (5, IH), 3.51 (5, 2H), 3.43 (d, J = 5.7 Hz, 4H), 3.39 (t, J= 2.8 Hz, 5H).2-Bromo-1, 1-dimethoxypropane (2a) (18 g, 98.34 mmol) was dissolved in chloroform (100 mL), trifluoroacetic acid (67.28 g, 590.03 mmol) was added and reacted at room temperature for 4 hours. The reaction solution was added with dichloromethane (30 mL) and water (15 mL), and the layers were extracted.The organic phase was washed with saturated brine (100 mL x 4), dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under reduced pressure at 30 C to give the title compound 2b as a yellow liquid (5 g, 37% yield).[0322] To a stirred solution of iV-hydroxy-6-methoxy-5-(4-methyl- 1H-imidazol- 1-yl) picolinimidamide (1 g, 4 mmol) in DMSO (5 mL) at 0 C under an argon atmosphere were added potassium hydroxide (272 mg, 5 mmol) and [0421] To a stirred solution of (Z)-5-bromo-iV-hydroxy-6-methoxypicolinimidamide (5 g, 20 mmol) in DMSO (50 mL) at 0 C under an argon atmosphere were added potassium hydroxide (1.7 g, 31 mmol) and 2-bromo- 1, 1 -dimethoxypropane (4.46 g, 24 mmol). The reaction mixture was warmed to room temperature and stirred for 48 h. After consumption of starting material (monitored by TLC), the reaction mixture was diluted with ice cold water (200 mL) and extracted with EtOAc (2 x 200 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by column chromatography using 20% EtOAc: Hexane to afford (Z)-5-bromo-iV-((1, 1- dimethoxypropan-2-yl)oxy)-6-methoxypicolinimidamide (930 mg, 13%) as pale yellow solid. 'H-NMR (CDC13, 400 MHz): 7.80 (d, 1H), 7.50 (d, 1H), 5.49 (br s, 2H), 4.50 (d, 1H), 4.3 1- 4.25 (m, 1H), 4.01 (s, 3H), 3.45 (s, 6H), 1.31 (d, 3H); TLC: 30% EtOAc/Hexane (Rj: 0.6)

Molecular Weight:183.04
XLogP3:1.3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:3
Exact Mass:181.99424
Monoisotopic Mass:181.99424
Topological Polar Surface Area:18.5
Heavy Atom Count:8
Complexity:54.4
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes