Diisopropylethylamine → HCID 67067674, compound

HRID 1037308Notes

Reaction equation

HRID 1037308 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][N:5]2[C:8](=[O:11])[NH:9][N:10]=[C:4]2[C:3]=1[O:12][CH3:13].BrC1C=CN2C(=O)NN=C2C=1O.CCN(C(C)C)C(C)C.Cl[CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41]>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][N:5]2[C:8](=[O:11])[N:9]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[N:10]=[C:4]2[C:3]=1[O:12][CH3:13]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 67067780HCID 67067780, compoundHCID 67067809HCID 67067809, compound

Product 1

HCID 67067674HCID 67067674, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred suspension of the mixture of 7-bromo-8-methoxy-2H-[1,2,4]triazolo[4,3-a]pyridin-3-one and 7-bromo-8-hydroxy-2H-[1,2,4]triazolo[4,3-a]pyridin-3-one (from step 4) in DCM (120 mL) at 0° C. was added DIPEA (35 mL, 0.2 mol). After 5 min, (2-chloromethoxy-ethyl)-trimethylsilane (11.9 mL, 67.2 mmol) was added. The mixture was stirred at 0° C. for 1 hour and at RT for a further 2 hours. The resulting mixture was diluted with DCM (200 mL) and washed successively with 0.5 M HCl (aq) (400 mL) and water, dried (Na2SO4), filtered, and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 15 to 30% ethyl acetate in cyclohexane) to afford the title compound (1.30 g, 20%) as a yellow solid. Fractions containing 7-bromo-8-(2-trimethylsilanyl-ethoxymethoxy)-2-(2-trimethylsilanyl-ethoxymethyl)-2H-[1,2,4]triazolo[4,3-a]pyridin-3-one were evaporated and the resultant residue was dissolved in MeOH (120 mL). The solution was stirred for 8 days at RT before evaporating to dryness. The resultant residue was dissolved in DMF (25 mL), cooled to 0° C., and cesium carbonate (13 g, 40 mmol) and iodomethane (3.11 mL, 50 mmol) were added. The reaction mixture was stirred at RT for 16 hours. EtOAc and water were added, the aqueous phase was isolated and extracted twice with EtOAc. The combined organic extracts were washed with water and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 15 to 30% EtOAc in cyclohexane) to afford a further quantity of the title compound (3.26 g, 51%) as a yellow solid. LCMS (Method A): RT=4.70 min, [M+H]+=396/398.

Workup

  1. washwashed successively with 0.5 M HCl (aq) (400 mL) and water
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-328c30a0acac472794623e1da0cb2f94
Source dataset
uspto-grants-2013_10
Patent number
US08546376B2

Reaction notes

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