Methyl iodide → 2-chloro-5-(2,2-difluoropropyl)-6a-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one

HRID 2386282Notes

Reaction equation

HRID 2386282 reaction equation
[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:12][C:13]([F:16])([F:15])[CH3:14])[C:7](=[O:17])[CH:6]3[CH2:18][O:19][CH2:20][CH2:21][N:5]3[C:4]=2[N:3]=1.IC.[CH3:24]C([O-])(C)C.[Na+]>CS(C)=O>[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:12][C:13]([F:16])([F:15])[CH3:14])[C:7](=[O:17])[C:6]3([CH3:24])[CH2:18][O:19][CH2:20][CH2:21][N:5]3[C:4]=2[N:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 23676156Sodium t-butoxideHCID 866515992-chloro-5-(2,2-difluoropropyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one

Product 1

HCID 781653442-chloro-5-(2,2-difluoropropyl)-6a-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-oneYield 54.3%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a mixture of 2-chloro-5-(2,2-difluoropropyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (466 mg, 1.46 mmol) and iodomethane (0.365 ml, 5.84 mmol) in DMSO (8 ml) at 0° C. was added sodium 2-methylpropan-2-olate (211 mg, 2.19 mmol). The ice-bath was removed and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was poured into water and extracted with EtOAc. The organic layers were washed with water (containing Na2S2O3), dried and concentrated in vacuo to give a crude solid. The solid was purified by silica gel chromatography (hexane/ethyl acetate, 19:1 to 2:1) to afford 2-chloro-5-(2,2-difluoropropyl)-6a-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (264 mg, 0.793 mmol, 54% yield) as a white solid. MS [M+H] found 333.

Workup

  1. customThe ice-bath was removed
  2. additionThe reaction mixture was poured into water
  3. extractionextracted with EtOAc
  4. washThe organic layers were washed with water (containing Na2S2O3)
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customto give a crude solid
  8. customThe solid was purified by silica gel chromatography (hexane/ethyl acetate, 19:1 to 2:1)

Sources & evidence

ORD record
ord-2f4423fcfa8247d7bad52fadea55f0e3
Source dataset
uspto-grants-2012_09
Patent number
US08268819B2

Reaction notes

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