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

HRID 2386285ノート

反応式

HRID 2386285 の反応式
[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:12][C:13]([F:16])([F:15])[F: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])[F: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

参加物

5

反応物 3

HCID 6328Methyl iodideHCID 23676156Sodium t-butoxideHCID 866516002-chloro-5-(2,2,2-trifluoroethyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one

生成物 1

HCID 866516012-chloro-6a-methyl-5-(2,2,2-trifluoroethyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one収率 24%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

実験手順

To a mixture of 2-chloro-5-(2,2,2-trifluoroethyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (768 mg, 2.38 mmol) and iodomethane (0.595 ml, 9.52 mmol) in DMSO (15 ml) at 0° C. was added sodium 2-methylpropan-2-olate (343 mg, 3.57 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 oil. The crude residue was purified by silica gel chromatography (hexane/ethyl acetate, 19:1 to 11:9) to afford 2-chloro-6a-methyl-5-(2,2,2-trifluoroethyl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-6(5H)-one (191 mg, 0.566 mmol, 24% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.41 (s, 3H) 3.17-3.28 (m, 1H) 3.55 (td, J=12.13, 3.03 Hz, 1H) 3.68 (d, J=11.62 Hz, 1H) 3.89-4.07 (m, 3H) 4.75-5.04 (m, 2H) 8.31 (s, 1H). MS [M+H] found 337.

後処理

  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 oil
  8. customThe crude residue was purified by silica gel chromatography (hexane/ethyl acetate, 19:1 to 11:9)

出典と根拠

ORDレコード
ord-820648c142fb40b0977e2a7e05731338
出典データセット
uspto-grants-2012_09
特許番号
US08268819B2

反応ノート

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