Potassium Phosphate, Tribasic → 9-cyclopentyl-N-(6-(4-pyridinyl)-3-pyridazinyl)-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

HRID 79239Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 79239
[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[N:21]=[N:20][C:19](Cl)=[CH:18][CH:17]=4)[N:13]=[CH:14][C:9]=3[C:8]3[CH:23]=[CH:24][N:25]=[CH:26][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.[N:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[N:21]=[N:20][C:19]([C:30]5[CH:31]=[CH:32][N:27]=[CH:28][CH:29]=5)=[CH:18][CH:17]=4)[N:13]=[CH:14][C:9]=3[C:8]3[CH:23]=[CH:24][N:25]=[CH:26][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1

Komponenten

7

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2734379(Pyridin-4-yl)boronic acidHCID 582996836-((9-cyclopentyl-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-chloro-pyridazine

Produkt 1

HCID 582999279-cyclopentyl-N-(6-(4-pyridinyl)-3-pyridazinyl)-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amineAusbeute 28 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of compound 140 (199 mg, 544 mop in dioxane (3 mL) were added pyridin-4-ylboronic acid (66.9 mg, 544 μmol), Pd2(dba)3 (24.9 mg, 27.2 μmol), tricyclohexylphosphine (15.3 mg, 54.4 μmol), and potassium phosphate (231 mg, 1.09 mmol) (in 1 mL of water). The reaction mixture was purged with N2 for 20 minutes and the reaction was heated at 100° C. degree for 18 hours. DCM was added to the reaction and the mixture was washed with water and brine. The organic layer was dried with sodium sulfate. The product was purified using Combiflash (DCM/methanol) followed by trituration with ethyl acetate to give compound 415 as a yellow solid (63 mg, 28%). 1H NMR (500 MHz, CD2Cl2) δ ppm 9.25 (1 H, s), 8.97-9.05 (2 H, m), 8.92 (1 H, s), 8.79 (2 H, d, J=6.1 Hz), 8.57 (1 H, d, J=5.1 Hz), 8.00-8.08 (3 H, m), 7.96 (1 H, dd, J=5.1, 1.2 Hz), 5.48 (1 H, quin, J=8.9 Hz), 2.48 (2 H, m), 2.20-2.28 (4 H, m), 1.95 (2 H, dddd, J=8.2, 4.5, 4.3, 4.2 Hz), 1.63 (2 H, br. s.); LCMS-ESI (POS), M/Z, M+1: Found 409.1, Calculated 409.2.

Aufarbeitung

  1. customThe reaction mixture was purged with N2 for 20 minutes
  2. additionDCM was added to the reaction
  3. washthe mixture was washed with water and brine
  4. dry with materialThe organic layer was dried with sodium sulfate
  5. customThe product was purified

Quellen und Nachweise

ORD-Eintrag
ord-07a33ef6b4174442b5fbf7061355a292
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08841312B2

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