Isopropanol → 6-Chloro-2-fluoro-9-isopropyl-9H-purine

HRID 928163노트

반응식

HRID 928163 반응식
[Cl:1][C:2]1[N:10]=[C:9]([F:11])[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][NH:6]2.[CH3:12][CH:13](O)[CH3:14].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>C1COCC1>[Cl:1][C:2]1[N:10]=[C:9]([F:11])[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH:13]([CH3:14])[CH3:12]

참가 물질

6

반응물 4

HCID 3776IsopropanolHCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 178506011HCID 178506011, 화합물

생성물 1

HCID 112873616-Chloro-2-fluoro-9-isopropyl-9H-purine수율 58.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

A solution of 6-chloro-2-fluoro-9H-purine (616 mg, 3.57 mmol) in THF (18 mL) was cooled in an ice water bath under nitrogen and iPrOH (858 mg, 14.3 mmol), triphenylphosphine, polymer-bound (2.38 g, 7.14 mmol, ˜3 mmol/g), and di-tert-butyl azodicarboxylate (1.730 g, 7.14 mmol) were added. The reaction mixture was allowed to warm to ambient temperature and stirred for 16 hr. The solid resin was removed and washed well with ethyl acetate (50 mL). The filtrate was concentrated down in vacuo to give a light yellow solid residue. This was then loaded onto silica and purified via flash chromatography (eluting with 30-50% ethyl acetate in heptanes) to give the title product as a white solid (445 mg, 58% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.83 (s, 1 H) 4.72-4.92 (m, 1 H) 1.57 (d, J=6.85 Hz, 6 H). m/z (APCI+) for C8H8FN4Cl 217.10, 215.10 (M+H)+.

후처리

  1. customThe solid resin was removed
  2. washwashed well with ethyl acetate (50 mL)
  3. concentrationThe filtrate was concentrated down in vacuo
  4. customto give a light yellow solid residue
  5. custompurified via flash chromatography (eluting with 30-50% ethyl acetate in heptanes)

출처 및 근거

ORD 기록
ord-c6ffe1bf2302480a889d69cd66991624
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09290496B2

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