N-Iodosuccinimide → HCID 86650629, 화합물

HRID 1963914노트

반응식

HRID 1963914 반응식
[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]

참가 물질

5

반응물 2

HCID 120273N-Iodosuccinimide2회HCID 534102886-Chloro-N-[(tetrahydro-2H-pyran-4-yl)methyl]-2-pyrazinamine

생성물 1

HCID 86650629HCID 86650629, 화합물수율 55.2%

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 962Water용매2회

반응 조건

온도
0 °C

실험 절차

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, 2 H) 1.59 (s, 2 H) 1.67 (d, J=12.91 Hz, 2 H) 1.77-1.94 (m, J=14.87, 7.63, 7.63, 3.52 Hz, 1 H) 3.25 (t, J=6.46 Hz, 2 H) 3.39 (td, J=11.74, 1.96 Hz, 2 H) 4.00 (dd, J=11.15, 3.72 Hz, 2 H) 4.80 (br. s., 1 H) 7.62 (s, 1 H).

후처리

  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

출처 및 근거

ORD 기록
ord-1563f91bc9194e5589caec452facc130
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415381B2

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