Isoamyl Nitrite → HCID 67252235, compound

HRID 44894Notes

Reaction equation

HRID 44894 reaction equation
N[C:2]1[S:3][C:4]([C:14]2[N:23]=[CH:22][C:21]3[N:20]([CH3:24])[C:19](=[O:25])[C@@H:18]([CH2:26][CH3:27])[N:17]([CH:28]([CH3:30])[CH3:29])[C:16]=3[N:15]=2)=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[N:6]=1.[Cu](C#N)[C:32]#[N:33].N(OCCC(C)C)=O>C(#N)C>[CH2:26]([C@H:18]1[N:17]([CH:28]([CH3:29])[CH3:30])[C:16]2[N:15]=[C:14]([C:4]3[S:3][C:2]([C:32]#[N:33])=[N:6][C:5]=3[C:7]3[CH:8]=[CH:9][C:10]([F:13])=[CH:11][CH:12]=3)[N:23]=[CH:22][C:21]=2[N:20]([CH3:24])[C:19]1=[O:25])[CH3:27]

Participants

5

Reactant 3

HCID 8053Isoamyl NitriteHCID 58405418HCID 58405418, compoundHCID 178418260HCID 178418260, compound

Product 1

HCID 67252235HCID 67252235, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (R)-2-(2-amino-4-(4-fluorophenyl)thiazol-5-yl)-7-ethyl-8-isopropyl-5-methyl-7,8-dihydropteridin-6(5H)-one (Example 318, 0.25 g, 0.586 mmol) and copper cyanide (0.054 g, 0.598 mmol) in 19 mL of anhydrous acetonitrile, isoamyl nitrite (0.1 ml, 0.751 mmol) was added. The reaction was placed in an oil bath set at 90° C. under condenser with N2 (g) inlet. The reaction mixture was stirred for 1 h, then cooled and quenched with water and extracted with EtOAc. The organic phase was collected, dried with sodium sulfate, filtered and concentrated. The resulting material was purified by preparative HPLC to give the title compound. LCMS: 437.1 m/z (M+H)+; ret. Time: 7.85 min (Analytical Method A). 1H NMR (CDCl3) δ: 7.83 (s, 1H), 7.69 (d, J=6 Hz, 1H), 7.67 (d, J=6 Hz, 1H), 7.15 (d, J=8 Hz, 1H), 7.13 (d, J=8 Hz, 1H), 4.33-4.28 (m, 1H), 4.20-4.14 (m, 1H), 3.37 (s, 3H), 2.07-2.02 (m, 1H), 1.94-1.85 (m, 1H), 1.24 (d, J=7 Hz, 3H), 1.13 (d, J=7 Hz, 3H), 0.84 (t, 3H).

Workup

  1. customThe reaction was placed in an oil bath
  2. customset at 90° C. under condenser with N2 (g) inlet
  3. temperaturecooled
  4. customquenched with water
  5. extractionextracted with EtOAc
  6. customThe organic phase was collected
  7. dry with materialdried with sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting material was purified by preparative HPLC

Sources & evidence

ORD record
ord-400420d8c2bd48c2b02d3dfb1c9f697f
Source dataset
uspto-grants-2013_09
Patent number
US08541418B2

Reaction notes

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