1-Ethyl-4-(prop-2-ynyl)piperazine → 4-{5-[3-(4-Methyl-piperazin-1-yl)-prop-1-ynyl]-pyridin-3-yl}-2-(6-methyl-pyridin-2-yl)-7H-pyrrolo[2,3-d]pyrimidine

HRID 1878603Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1878603
Br[C:2]1[CH:3]=[C:4]([C:8]2[C:9]3[CH:23]=[CH:22][NH:21][C:10]=3[N:11]=[C:12]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[N:15]=3)[N:13]=2)[CH:5]=[N:6][CH:7]=1.[CH2:24]([N:26]1[CH2:31][CH2:30][N:29]([CH2:32][C:33]#[CH:34])[CH2:28][CH2:27]1)C>COCCOC.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:24][N:26]1[CH2:31][CH2:30][N:29]([CH2:32][C:33]#[C:34][C:2]2[CH:3]=[C:4]([C:8]3[C:9]4[CH:23]=[CH:22][NH:21][C:10]=4[N:11]=[C:12]([C:14]4[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[N:15]=4)[N:13]=3)[CH:5]=[N:6][CH:7]=2)[CH2:28][CH2:27]1

Komponenten

6

Edukt 2

HCID 211907411-Ethyl-4-(prop-2-ynyl)piperazineHCID 441944484-(5-Bromo-pyridin-3-yl)-2-(6-methyl-pyridin-2-yl)-7H-pyrrolo[2,3-d]pyrimidine

Produkt 1

HCID 441950084-{5-[3-(4-Methyl-piperazin-1-yl)-prop-1-ynyl]-pyridin-3-yl}-2-(6-methyl-pyridin-2-yl)-7H-pyrrolo[2,3-d]pyrimidine

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

To a suspension of of 4-(5-bromo-pyridin-3-yl)-2-(6-methyl-pyridin-2-yl)-7H-pyrrolo[2,3-d]pyrimidine (Example 16) (1 eq, 0.669 mmol, 245 mg) in DME (3.5 ml) are added TEA (2 eq, 1.34 mmol, 135 mg), copper (I) iodide (0.5 eq, 0.335 mmol, 63.7 mg), Pd(PPh3)4 (0.1 eq, 0.067 mmol, 77 mg), and 1-ethyl-4-prop-2-ynyl-piperazine (Tyger Scientific, Ewing, USA) (1 eq, 0.669 mmol, 92 mg). The resulting mixture is heated using microwave radiation for 20 min at 120° C. The mixture is filtered through a pad of Celite and concentrated under reduced pressure. 2M aqueous HCl is added, and the mixture is washed with DCM. The aqueous layer is adjusted to pH 10 using 2M aqueous NaOH, and extracted with DCM. The organic layer is dried over MgSO4, and the solvents are removed in vacuo. The crude mixture is purified using reversed phase HPLC to give the title compound; [M+H]+=424; 1H-NMR (400 MHz, CD3OD): δ 12.23 (s, 1H), 9.40 (d, 1H), 8.79 (d, 1H), 8.66 (d, 1H), 8.61 (t, 1H), 7.85 (t, 1H), 7.45 (t, 1H), 7.32 (d, 1H), 6.85 (m, 1H), 3.60 (s, 2H), 2.74 (s, 3H), 2.70-2.50 (m, 8H), 2.33 (s, 3H).

Aufarbeitung

  1. temperatureThe resulting mixture is heated
  2. customfor 20 min
  3. customat 120° C
  4. filtrationThe mixture is filtered through a pad of Celite
  5. concentrationconcentrated under reduced pressure
  6. addition2M aqueous HCl is added
  7. washthe mixture is washed with DCM
  8. extractionextracted with DCM
  9. dry with materialThe organic layer is dried over MgSO4
  10. customthe solvents are removed in vacuo
  11. customThe crude mixture is purified

Quellen und Nachweise

ORD-Eintrag
ord-f77b9ff42dfc44b8b361e8053db936e9
Quelldatensatz
uspto-grants-2012_11
Patentnummer
US08314112B2

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