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

HRID 1260444Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1260444
[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

Komponenten

6

Edukt 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

Produkt 1

HCID 24963597(R)-3-(2,3-Dihydroxypropyl)-5-(4-ethynyl-2-fluorophenylamino)-6,8-dimethylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dioneAusbeute 74,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 83717Copper iodideKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

(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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-9759262fdfcb40e19608b565f4632a73
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08470837B2

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