Sodium hydride → 2-((5-Bromopyrimidin-2-yloxy)methyl)-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole

HRID 2066630Notes

Reaction equation

HRID 2066630 reaction equation
[CH3:1][C:2]1([CH2:13][OH:14])[O:6][C:5]2=[N:7][C:8]([N+:10]([O-:12])=[O:11])=[CH:9][N:4]2[CH2:3]1.[Br:15][C:16]1[CH:17]=[N:18][C:19](Cl)=[N:20][CH:21]=1.[H-].[Na+]>CN(C=O)C>[Br:15][C:16]1[CH:17]=[N:18][C:19]([O:14][CH2:13][C:2]2([CH3:1])[O:6][C:5]3=[N:7][C:8]([N+:10]([O-:12])=[O:11])=[CH:9][N:4]3[CH2:3]2)=[N:20][CH:21]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 6066655-Bromo-2-chloropyrimidineHCID 23081240(2-Methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-yl)methanol

Product 1

HCID 669556012-((5-Bromopyrimidin-2-yloxy)methyl)-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of alcohol 101 (see Example 2M) (100 mg, 0.502 mmol) and 5-bromo-2-chloropyrimidine (156 mg, 0.806 mmol) in anhydrous DMF (2.5 mL) under N2 at 0° C. was treated with 60% NaH (32 mg, 0.80 mmol), then quickly degassed and resealed under N2. After stirring at room temperature for 140 min, the reaction was cooled (CO2/acetone), quenched with ice/aqueous NaHCO3 (10 mL), added to brine (40 mL), and extracted with CH2Cl2 (6×50 mL). The combined extracts were evaporated to dryness and the residue was chromatographed on silica gel. Elution with 0-0.25% MeOH/CH2Cl2 firstly gave foreruns, and then further elution with 0.25-0.5% MeOH/CH2Cl2 gave 2-{[(5-bromo-2-pyrimidinyl)oxy]methyl}-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole (103) (reported by Ding et al., WO 2009120789A1 from 101 via a similar procedure) (163 mg, 91%) as a cream solid: mp (MeOH/CH2Cl2/hexane) 224-226° C.; 1H NMR [(CD3)2SO] δ 8.77 (s, 2H), 8.14 (s, 1H), 4.61 (s, 2H), 4.41 (d, J=11.0 Hz, 1H), 4.20 (d, J=11.1 Hz, 1H), 1.70 (s, 3H). Anal. (C11H10BrN5O4) C, H, N.

Workup

  1. customat 0° C.
  2. customquickly degassed
  3. temperaturethe reaction was cooled (CO2/acetone)
  4. customquenched with ice/aqueous NaHCO3 (10 mL)
  5. additionadded to brine (40 mL)
  6. extractionextracted with CH2Cl2 (6×50 mL)
  7. customThe combined extracts were evaporated to dryness
  8. customthe residue was chromatographed on silica gel
  9. washElution with 0-0.25% MeOH/CH2Cl2 firstly gave foreruns
  10. washfurther elution with 0.25-0.5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-3b0d916508264f0d9b1af04c038f2f35
Source dataset
uspto-grants-2012_10
Patent number
US08293734B2

Reaction notes

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