N-Iodosuccinimide → HCID 86650629、化合物

HRID 1623341ノート

反応式

HRID 1623341 の反応式
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[CH:5]=[N:4][CH:3]=1.[I:16]N1C(=O)CCC1=O>CS(C)=O.O>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[CH:5]=[N:4][C:3]=1[I:16]

参加物

5

反応物 2

HCID 120273N-Iodosuccinimide2 回HCID 534102886-Chloro-N-[(tetrahydro-2H-pyran-4-yl)methyl]-2-pyrazinamine

生成物 1

HCID 86650629HCID 86650629、化合物収率 55.2%

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒2 回

反応条件

温度
0 °C

実験手順

6-chloro-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine (0.250 g, 1.098 mmol) was dissolved in a mixture of DMSO (4.30 ml) and H2O (0.105 ml). It was cooled to 0° C. in an ice bath and was then treated with N-iodosuccinimide (0.247 g, 1.098 mmol) by portion-wise addition. Once the addition was complete the reaction mixture was stirred at ambient temperature for 24 hr. Additional NIS (0.025 g, 0.111 mmol) was added. Stirring at ambient temperature was continued for 24 hr. The reaction mixture was diluted with H2O (50 ml). This was extracted with EtOAc (3×50 ml). The organic layers were combined and washed with brine (1×50 ml). The organic layer was dried (Na2SO4), filtered, and the solvent removed in vacuo to give 0.410 g of crude product. The resulting residue was subjected to silica gel column chromatography. Elution using 30 EtOAc/70 heptane to 100 EtOAc gave 0.2144 g (55%) of 6-chloro-5-iodo-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine. LCMS (m/z): 353.9 (MH+), retention time=0.92 min. 1H NMR (400 MHz, CHLOROFORM-d) d ppm 1.37 (qd, 2H) 1.59 (s, 2H) 1.67 (d, J=12.91 Hz, 2H) 1.77-1.94 (m, J=14.87, 7.63, 7.63, 3.52 Hz, 1H) 3.25 (t, J=6.46 Hz, 2H) 3.39 (td, J=11.74, 1.96 Hz, 2H) 4.00 (dd, J=11.15, 3.72 Hz, 2H) 4.80 (br. s., 1H) 7.62 (s, 1H).

後処理

  1. additionOnce the addition
  2. stirringStirring at ambient temperature
  3. waitwas continued for 24 hr
  4. extractionThis was extracted with EtOAc (3×50 ml)
  5. washwashed with brine (1×50 ml)
  6. dry with materialThe organic layer was dried (Na2SO4)
  7. filtrationfiltered
  8. customthe solvent removed in vacuo
  9. customto give 0.410 g of crude product
  10. washElution

出典と根拠

ORDレコード
ord-f6f8dbc289ea4a089f71389e3852a4ad
出典データセット
uspto-grants-2014_07
特許番号
US08778951B2

反応ノート

読み込み中…