Triethylamine → (R)-3-(2,3-Dihydroxypropyl)-5-(4-ethynyl-2-fluorophenylamino)-6,8-dimethylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione

HRID 1660896Notes

Reaction equation

HRID 1660896 reaction equation
[OH:1][C@@H:2]([CH2:27][OH:28])[CH2:3][N:4]1[C:9](=[O:10])[C:8]2[C:11]([NH:18][C:19]3[CH:24]=[CH:23][C:22](I)=[CH:21][C:20]=3[F:26])=[C:12]([CH3:17])[C:13](=[O:16])[N:14]([CH3:15])[C:7]=2[N:6]=[CH:5]1.C[Si]([C:33]#[CH:34])(C)C.C(N(CC)CC)C>C1COCC1.[Cu](I)I>[OH:1][C@@H:2]([CH2:27][OH:28])[CH2:3][N:4]1[C:9](=[O:10])[C:8]2[C:11]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([C:33]#[CH:34])=[CH:21][C:20]=3[F:26])=[C:12]([CH3:17])[C:13](=[O:16])[N:14]([CH3:15])[C:7]=2[N:6]=[CH:5]1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 24966075(R)-3-(2,3-Dihydroxypropyl)-5-(2-fluoro-4-iodophenylamino)-6,8-dimethylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione

Product 1

HCID 24963597(R)-3-(2,3-Dihydroxypropyl)-5-(4-ethynyl-2-fluorophenylamino)-6,8-dimethylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dioneYield 74.7%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

(R)-3-(2,3 Dihydroxypropyl)-5-(2-fluoro-4-iodophenylamino)-6,8-dimethylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (200 mg, 0.4 mmol, Example 8), trimethylsilyl acetylene (66 μL, 0.6 mmol), triethylamine (84 μL, 0.6 mmol), copper iodide (14 mg, cat) and dichlorobis(triphenylphoshine) palladium(II) (14 mg, 0.02 mmol) were mixed in THF (2 mL). The mixture was subjected to microwave irradiation at 120° C. for 20 minutes. The solvent was removed in vacuo and the residue dissolved in methanol. Potassium carbonate (50 mg) was added and the solution stirred at RT for 1 hour. After filtration and evaporation the residue was purified by HPLC to give 119 mg of the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 1.79 (s, 3H) 3.11 (s, 1H) 3.54-3.66 (m, 3H) 3.82-3.90 (m, 1H) 3.94-4.02 (m, 1H) 4.30 (dd, J=14.15, 3.79 Hz, 1H) 6.67 (t, J=8.46 Hz, 1H) 7.19 (dd, J=8.21, 0.88 Hz, 1H) 7.21-7.25 (m, 1H) 8.27 (s, 1H) [M+H] calc'd for C20H19FN4O4, 399; found, 399.

Workup

  1. customirradiation at 120° C. for 20 minutes
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue dissolved in methanol
  4. additionPotassium carbonate (50 mg) was added
  5. filtrationAfter filtration and evaporation the residue
  6. customwas purified by HPLC

Sources & evidence

ORD record
ord-2e975eb976bb4543b7c64384883859dc
Source dataset
uspto-grants-2011_10
Patent number
US08030317B2

Reaction notes

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