Sodium hydride → 6-(2,4-Difluorophenyl)-5-(3-(2-(2-methoxyethoxy)propan-2-yl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)imidazo[2,1-b]oxazole

HRID 1930010Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[N:15]([C:16]=1[C:17]1[CH:18]=[CH:19][C:20]3[N:21]([C:23]([C:26]([OH:29])([CH3:28])[CH3:27])=[N:24][N:25]=3)[N:22]=1)[CH:14]=[CH:13][O:12]2.[H-].[Na+].Br[CH2:33][CH2:34][O:35][CH3:36]>C1COCC1.CN(C=O)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[N:15]([C:16]=1[C:17]1[CH:18]=[CH:19][C:20]3[N:21]([C:23]([C:26]([O:29][CH2:33][CH2:34][O:35][CH3:36])([CH3:27])[CH3:28])=[N:24][N:25]=3)[N:22]=1)[CH:14]=[CH:13][O:12]2

Participants

Conditions

Temperature: 70 °C

Procedure

In a 10 mL pear flask, 2-(6-(6-(2,4-difluorophenyl)imidazo[2,1-b]oxazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)propan-2-ol (0.100 g, 0.252 mmol, Example #37) and NaH (60% in mineral oil, 0.025 g, 0.631 mmol) in THF (5 mL) and DMF (1 mL) were added to give an off-white suspension. 1-Bromo-2-methoxyethane (0.140 g, 1.01 mmol) was then added and the suspension was stirred at about 70° C. for about 17 h. The mixture was concentrated under reduced pressure and was purified by flash chromatography on silica gel MeOH/DCM (gradient 1-5% over 14 min) and then further purified by RP-HPLC (Table 1, Method m) to afford the title compound (0.012 g, 11%) as a white fluffy solid: LC/MS (Table 1, Method g) Rt=2.02 min; MS m/z 455.2 (M+H)+.

Workup

customto give an off-white suspension
concentrationThe mixture was concentrated under reduced pressure
customwas purified by flash chromatography on silica gel MeOH/DCM (gradient 1-5% over 14 min)
customfurther purified by RP-HPLC (Table 1, Method m)

Sources & evidence

ORD record: ord-b389200f63474944ae34c66640d0ba34
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08188083B2

Reaction notes

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