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

HRID 1695990Notes

Reaction equation

HRID 1695990 reaction equation
[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH:12]([CH3:14])[CH3:13])[C:7](=[O:15])[CH:6]3[CH2:16][O:17][CH2:18][CH2:19][N:5]3[C:4]=2[N:3]=1.IC.[CH3:22]C([O-])(C)C>CS(C)=O.O>[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH:12]([CH3:13])[CH3:14])[C:7](=[O:15])[C:6]3([CH3:22])[CH2:16][O:17][CH2:18][CH2:19][N:5]3[C:4]=2[N:3]=1

Participants

6

Reactant 3

HCID 6328Methyl iodide2×HCID 45749132-Methylpropan-2-olate2×HCID 866515702-chloro-5-isopropyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one

Product 1

HCID 866515712-chloro-5-isopropyl-6a-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-oneYield 8%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolvent

Procedure

2-Chloro-5-isopropyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (1.20 g, 4.24 mmol) and iodomethane (1.324 mL, 21.22 mmol) were mixed in DMSO. The mixture was frozen, 2-methylpropan-2-olate (1.224 g, 12.73 mmol) was added, covered by a layer of DMSO and refrozen. The mixture was allowed to room temperature and stirred overnight. Another 1 eq of 2-methylpropan-2-olate and iodomethane was added and the mixture stirred overnight at 30° C. The solution was diluted with water and extracted with EtOAc twice. The organic layers were combined, dried over magnesium sulfate, filtered, and evaporated in vacuo. The residue was absorbed onto silica and purified by column chromatography using 10-60% EtOAc in hexanes then 5% methanol in dichloromethane as eluent. Relevant fractions were evaporated in vacuo to give 98 mg (8%) 2-chloro-5-isopropyl-6a-methyl-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one. MS [M+H] Found 297.

Workup

  1. temperatureThe mixture was frozen
  2. customwas allowed to room temperature
  3. stirringthe mixture stirred overnight at 30° C
  4. extractionextracted with EtOAc twice
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe residue was absorbed onto silica
  9. custompurified by column chromatography
  10. customRelevant fractions were evaporated in vacuo

Sources & evidence

ORD record
ord-832b87f88a9141c4956e69a504308271
Source dataset
uspto-grants-2012_04
Patent number
US08163755B2

Reaction notes

Loading…