Sodium hydride → HCID 86651579, compound

HRID 2386255Notes

Reaction equation

HRID 2386255 reaction equation
[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[NH:8][C:7](=[O:12])[C@H:6]3[CH2:13][O:14][CH:15]([CH3:17])[CH2:16][N:5]3[C:4]=2[N:3]=1.[H-].[Na+].Br[CH2:21][CH:22]1[CH2:24][CH2:23]1>CN(C=O)C.CCOC(C)=O.O>[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:21][CH:22]3[CH2:24][CH2:23]3)[C:7](=[O:12])[C@H:6]3[CH2:13][O:14][CH:15]([CH3:17])[CH2:16][N:5]3[C:4]=2[N:3]=1

Participants

7

Reactant 3

HCID 24758Sodium hydride2×HCID 81503Bromomethylcyclopropane3×HCID 86651580HCID 86651580, compound

Product 1

HCID 86651579HCID 86651579, compoundYield 99.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (R)-2-chloro-9-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (103 mg, 0.404 mmol) in DMF (2.5 mL) at 0° C. was added sodium hydride (21 mg, 0.526 mmol, 60% in oil). After 35 minutes at 0° C., (bromomethyl)cyclopropane (0.051 mL, 0.526 mmol) was added. The mixture was stirred at 0° C. for 30 minutes, then at room temperature for 45 minutes and then sealed and heated at 90° C. (bath temperature) for 2 hours. More (bromomethyl)cyclopropane (0.250 mL) was added and heated at 90° C. for another 24 hours. The mixture was cooled to room temperature, and more sodium hydride (excess) was added followed by (bromomethyl)cyclopropane (0.1 mL). Heating was continued at 90° C. for another 6 hours. Then the mixture was diluted with EtOAc and water, extracted with EtOAc (3×), and dried over Na2SO4. Solvent was removed in vacuo to give crude (R)-2-chloro-5-(cyclopropylmethyl)-9-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one as a brown oil (124 mg). MS [M+H] found 309.2.

Workup

  1. waitat room temperature for 45 minutes
  2. customsealed
  3. temperatureheated at 90° C. (bath temperature) for 2 hours
  4. temperatureheated at 90° C. for another 24 hours
  5. temperatureThe mixture was cooled to room temperature
  6. temperatureHeating
  7. waitwas continued at 90° C. for another 6 hours
  8. extractionextracted with EtOAc (3×)
  9. dry with materialdried over Na2SO4
  10. customSolvent was removed in vacuo

Sources & evidence

ORD record
ord-17b89cb916754ff3a91e4ad25c894c78
Source dataset
uspto-grants-2012_09
Patent number
US08268819B2

Reaction notes

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