As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 90993-26-3, name is 7-Bromo-1H-imidazo[4,5-c]pyridine, molecular formula is C6H4BrN3, The compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below. SDS of cas: 90993-26-3
Step 3: 7-bromo-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazo[4,5-c]pyridine 5-oxide To a stirred solution of 7-bromo-lH-imidazo[4,5-c]pyridine 5-oxide (425 mg, 1.99 mmol) and N,N- dimethylformaldehyde (5.5 mL) at 0 C was added N,N-diisopropylethylamine (1.05 mL, 5.96 mmol), tetrabutylammonium iodide (74 mg, 0.199 mmol) and 2-(trimethylsilyl)ethoxymethyl chloride (0.78 mL, 3.97 mmol) and the reaction mixture stirred for 30 min at RT. The reaction mixture was washed with water (10 mL) and extracted with dichloromethane (2 x 10 mL). The combined organic layers were dried over sodium sulfate and concentrated to dryness in vacuo. The resulting residue was purified by column chromatography (silica gel, 100-200 mesh, 0 to 10% methanol in dichloromethane) affording an approximate 3:2 mixture of 7-bromo-l-((2- (trimethylsilyl)ethoxy)methyl)-lH-imidazo[4,5-c]pyridine 5-oxide and 7-bromo-3-((2- (trimethylsilyl)ethoxy)methyl)-3H-imidazo[4,5-c]pyridine 5-oxide N-(2- (trimethylsilyl)ethoxy)methane regioisomers as an orange foam (580 mg, 54%): H NMR (400 MHz, DMSO-d6; reported as an approximate 3:2 mixture of N-(2-(trimethylsilyl)ethoxy)methane isomers) delta 8.73 (d, = 1.5 Hz, 0.6 H), 8.60 (d, = 1.6 Hz, 1H), 8.38 (d, = 1.5 Hz, 1H), 8.36 (d, = 1.5 Hz, 0.6H), 8.10 (s, 1H), 8.09 (s, 0.6H), 5.76 (s, 1.3H), 5.48 (s, 2H), 3.63 – 3.59 (m, 1.4H), 3.56 – 3.50 (m, 2H), 0.97 – 0.91 (m, 3H), -0.01 (s, 9H), -0.02 (s, 6H). Step 4: 7-bromo-N-(tert-butyl)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazo[4,5-c]pyrid^ amine To a stirred solution of 7-bromo-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazo[4,5-c]pyridine 5- oxide (102 mg, 0.296 mmol) and 1 ,2-dichloroethane (1.5 niL) was added N,N-diisopropylethylamine (0.195 niL, 1.11 mmol), i-butylamine (0.039 mL, 0.37 mmol) and bromotripyrrolidinophosphonium hexafluorophosphate (180 mg, 0.385 mmol) and the reaction mixture stirred for 22 h at RT. The reaction mixture was washed with saturated sodium bicarbonate solution (10 mL) and extracted with dichlorome thane (2 x 10 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated to dryness in vacuo. The resulting residue was purified by column chromatography (silica gel, 100-200 mesh, 0 to 50% ethyl acetate in heptane) affording an approximate 3:2 mixture of 7-bromo-N-(tert-butyl)-l-((2-(trimethy and 7-bromo-N-(tert-butyl)-3-((2-(trimethylsilyl)ethoxy)methyl)-3H-imidazo[4,5-c]pyridin-4-amine N- SEM regioisomers (47 mg, 40%): H NMR (400 MHz, DMSO-d6; reported as an approximate 3:2 mixture of N-SEM isomers) delta 8.00 (s, 0.7H), 7.95 (s, 1H), 7.81 (s, 0.7H), 7.77 (s, 1H), 6.02 (br s, 0.8H), 5.77 (s, 2H), 5.54 (s, 1.6H), 5.43 (br s, 1H), 3.63 – 3.57 (m, 3.7H), 1.02 – 0.89 (m, 3.8H), 0.00 (s, 6H), -0.02 (s, 9H). Step 5: N-(tert-butyl)-7-(4-cyclopropyl-6,6-dimethyl-8,9-dihydro-6H-[l,4]oxazino[4,3-e]purin-2- yl)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazo[4,5-c]pyridin-4-amine 4-cyclopropyl-6,6-dimethyl-2-(tributylstannyl)-8,9-dihydro-6H-[l,4]oxazino[4,3-e]purine (64.5 mg, 0.12 mmol) and 7-bromo-N-(tert-butyl)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazo[4,5- c]pyridin-4-amine (46 mg, 0.115 mmol) were dissolved in 1,4-dioxane (2.5 mL) in a microwave vial equipped with a stir bar and the mixture was purged with nitrogen gas for 10 min. Copper(I) thiophene-2-carboxylate (22 mg, 0.115 mmol) and tetrakis(triphenylphosphine)palladium(0) (13.3 mg, 0.012 mmol) were then added and the reaction mixture was microwaved at 140 C for 35 min. The reaction mixture was filtered through a celite bed and washed with dichlorome thane (10 mL). The filtrate was concentrated to dryness in vacuo, dissolved in ethyl acetate and washed with brine (10 niL). The organic layer was separated, dried over sodium sulfate and concentrated to afford crude N-(tert-butyl)-7-(4-cyclopropyl-6,6-dimethyl-8,9-dihydro-6H-[l,4]oxazino[4,3-e]purin-2-yl)-l-((2- (trimethylsilyl)ethoxy)methyl)-lH-imidazo[4,5-c]pyridin-4-amine used for the next step without any further purification.
With the rapid development of chemical substances, we look forward to future research findings about 90993-26-3.
Reference:
Patent; F. HOFFMANN-LA ROCHE AG; GENENTECH, INC.; ESTRADA, Anthony; HUESTIS, Malcolm; KELLAR, Terry; PATEL, Snahel; SHORE, Daniel; SIU, Michael; (260 pag.)WO2016/142310; (2016); A1;,
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