Cesium carbonate → 8-(5-chloro-2-(1-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-one

HRID 1045945

Reaktionsgleichung

Reaktionsgleichung von HRID 1045945
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:10]=[CH:11][CH:12]=[C:13]3[C:18]=2[C:17](=[O:19])[N:16]([CH3:20])[CH2:15][CH2:14]3)[C:5]([Cl:21])=[CH:4][N:3]=1.[CH3:22][N:23]1[C:27]([NH2:28])=[CH:26][CH:25]=[N:24]1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:21][C:5]1[C:6]([NH:8][C:9]2[CH:10]=[CH:11][CH:12]=[C:13]3[C:18]=2[C:17](=[O:19])[N:16]([CH3:20])[CH2:15][CH2:14]3)=[CH:7][C:2]([NH:28][C:27]2[N:23]([CH3:22])[N:24]=[CH:25][CH:26]=2)=[N:3][CH:4]=1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 1369272-Methyl-2H-pyrazol-3-ylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 866551378-[(2,5-Dichloropyridin-4-yl)amino]-2-methyl-3,4-dihydroisoquinolin-1-one

Produkt 1

HCID 446090408-(5-chloro-2-(1-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-oneAusbeute 69,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

8-[(2,5-Dichloropyridin-4-yl)amino]-2-methyl-3,4-dihydroisoquinolin-1-one (100 mg, 0.31 mmol, example 3.23), 1-Methylpyrazol-5-amine (60.3 mg, 0.62 mmol), cesium carbonate (121 mg, 0.37 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (28.7 mg, 0.05 mmol) and palladium(II) acetate (5.57 mg, 0.02 mmol) were suspended in dioxane (2 mL) and sealed in a tube. The reaction was degased, purged with nitrogen and heated to 100° C. for 12 hours. The reaction mixture was filtered, washed with DCM and concentrated to dryness. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (5 microns silica, 30 mm diameter, 150 mm length) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions were evaporated to dryness to afford 8-(5-chloro-2-(1-methyl-1H-pyrazol-5-ylamino)pyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (83 mg, 69.8%) as a grey solid. 1H NMR spectrum (500 MHz, DMSO): 2.95 (t, 2H), 3.05 (s, 3H), 3.56 (t, 2H), 3.63 (s, 3H), 6.19 (d, 1H), 6.86 (s, 1H), 6.91 (dd, 1H), 7.29 (d, 1H), 7.42 (s, 1H), 7.43 (d, 1H), 8.02 (s, 1H), 8.68 (s, 1H), 11.26 (s, 1H); Mass spectrum: ESI+ MH+ 383.

Aufarbeitung

  1. customsealed in a tube
  2. customThe reaction was degased
  3. custompurged with nitrogen
  4. filtrationThe reaction mixture was filtered
  5. washwashed with DCM
  6. concentrationconcentrated to dryness
  7. customThe reaction mixture was purified by preparative HPLC
  8. customThe fractions were evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-ea761b39e4154415b5a109134833248a
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08569298B2

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