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

HRID 928163Notes

Reaction equation

HRID 928163 reaction equation
[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]

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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)+.

Workup

  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)

Sources & evidence

ORD record
ord-c6ffe1bf2302480a889d69cd66991624
Source dataset
uspto-grants-2016_03
Patent number
US09290496B2

Reaction notes

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