Sodium hydride → HCID 54437236, compound

HRID 1432932Notes

Reaction equation

HRID 1432932 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][NH:11][C:10](=[O:14])[CH2:9]1)=O)(C)(C)C.[I-].[H-].[Na+].Br[CH2:19][C:20]1[CH:29]=[C:28]2[C:23]([C:24]([Cl:30])=[CH:25][N:26]=[N:27]2)=[CH:22][CH:21]=1>C1COCC1>[Cl:30][C:24]1[C:23]2[C:28](=[CH:29][C:20]([CH2:19][N:11]3[CH2:12][CH2:13][NH:8][CH2:9][C:10]3=[O:14])=[CH:21][CH:22]=2)[N:27]=[N:26][CH:25]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 30165Iodide IonHCID 3157178Tert-butyl 3-oxopiperazine-1-carboxylateHCID 540103687-Bromomethyl-4-chlorocinnoline

Product 1

HCID 54437236HCID 54437236, compoundYield 59.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

4-(t-Butyloxycarbonyl)-piperazin-2-one (0.6 g, 3.0 mmol), EXAMPLE 40, is dissolved in THF (80 mL), cooled in an ice bath and treated with tretrabutylammonium iodide (0.23 g, 0.62 mmol) and 60% sodium hydride (0.12 g, 3.0 mmol). The reaction mixture is stirred at ° C. for 40 minutes then treated dropwise with a solution of 7-bromomethyl-4-chlorocinnoline (10.7 g, 2.7 mmol), Example 15, in THF (20 mL). The resulting solution is warmed to ambient temperature over 2 hours. The solution is evaporated to dryness and the residue is taken up in ethyl acetate and 10% aqueous sodium bicarbonate solution. The organic layer is separated, washed with water, dried (sodium sulfate) and concentrated. The residue is chromatographed (ethyl acetate) to yield the title compound (0.6 g, 1.6 mmol). A portion of this material (0.21 g, 1.26 mmol) is dissolved in THF (˜4 mL) and treated with a saturated solution of HCl in ethyl acetate (50 mL) at room temperature for 2 hours. The solution is filtered and concentrated to a residue (0.14 g, 0.4 mmol). MS m/z: M+=275; 1H NMR (CD3OD, 300 MHz) δ9.15 (d, 1H), 8.5 (d, 1H), 8.25 (s, 1H), 8.15 (d, 1H), 8.0 (d, 1H), 5.0 (s, 2H), 4.1 (s, 2H), 3.7-3.8 (m, 2H), 3.6-3.7 (m, 2H).

Workup

  1. temperaturecooled in an ice bath
  2. customThe solution is evaporated to dryness
  3. customThe organic layer is separated
  4. washwashed with water
  5. dry with materialdried (sodium sulfate)
  6. concentrationconcentrated
  7. customThe residue is chromatographed (ethyl acetate)

Sources & evidence

ORD record
ord-399e0461f8ef4afabc7cd08b9cf00327
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

Loading…