Sodium hydride → HCID 86679607, 화합물

HRID 577660노트

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HRID 577660 반응식
[Cl:1][C:2]1[N:3]=[C:4]([Cl:12])[C:5]2[C:10]([F:11])=[CH:9][NH:8][C:6]=2[N:7]=1.[H-].[Na+].Cl[CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21]>CN(C=O)C>[Cl:1][C:2]1[N:3]=[C:4]([Cl:12])[C:5]2[C:10]([F:11])=[CH:9][N:8]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[C:6]=2[N:7]=1

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 594420712,4-Dichloro-5-fluoro-7H-pyrrolo[2,3-d]pyrimidine

생성물 1

HCID 86679607HCID 86679607, 화합물수율 42%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

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온도
0 °C

실험 절차

2,4-Dichloro-5-fluoro-7H-pyrrolo[2,3-d]pyrimidine (see Seela, et al., Helvetica Chimica Acta, 91(6):1083-1105 (2008)) (654 mg, 3.2 mmol) was dissolved in DMF (6.5 mL). After cooling to 0° C., NaH (254 mg, 6.35 mmol, 60% in mineral oil) was added. After complete addition, the mixture was warmed to rt and allowed to stir for 30 min. A solution of (2-(chloromethoxy)ethyl)trimethylsilane (529 mg, 3.2 mmol) in DMF (2 mL) was added dropwise to the mixture and stirring was continued for 3 hrs. The reaction was quenched by pouring the mixture over ice water (75 mL). The resulting aqueous layer was then extracted with Et2O (three×50 mL). The combined organics were washed with water (two times), brine (two times) and dried over MgSO4. After concentrating, the brown solid was purified via flash chromatography eluting with a gradient of 1%-10% EtOAc in heptanes to afford the title compound (0.45 g, 42% yield) as a white, low melting solid. 1H NMR (400 MHz, chloroform-d) δ ppm-0.03 (s, 9H), 0.87-0.97 (m, 2H), 3.48-3.58 (m, 2H), 5.57 (s, 2H), 7.14 (d, J=2.78 Hz, 1H). APCI (MH+). m/z (APCI+) for C12H16Cl2FN3OSi 336.2 (M+H)+.

후처리

  1. additionAfter complete addition
  2. temperaturethe mixture was warmed to rt
  3. stirringstirring
  4. waitwas continued for 3 hrs
  5. customThe reaction was quenched
  6. additionby pouring the mixture over ice water (75 mL)
  7. extractionThe resulting aqueous layer was then extracted with Et2O (three×50 mL)
  8. washThe combined organics were washed with water (two times), brine (two times)
  9. dry with materialdried over MgSO4
  10. concentrationAfter concentrating
  11. customthe brown solid was purified via flash chromatography
  12. washeluting with a gradient of 1%-10% EtOAc in heptanes

출처 및 근거

ORD 기록
ord-2b94fc42d06e4beca7dc36344dae1df0
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09040547B2

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