Sodium Carbonate → 4-(9-methyl-6-morpholino-8-((4-morpholinopiperidin-1-yl)methyl)-9H-purin-2-yl)isoquinolin-1-amine

HRID 1945729Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1945729
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][N:13]3[CH2:18][CH2:17][CH:16]([N:19]4[CH2:24][CH2:23][O:22][CH2:21][CH2:20]4)[CH2:15][CH2:14]3)[N:8]2[CH3:11])=[C:4]([N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[N:3]=1.CC1(C)C(C)(C)OB([C:39]2[C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[C:42]([NH2:49])=[N:41][CH:40]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.CCOC(C)=O.O.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>[CH3:11][N:8]1[C:7]([CH2:12][N:13]2[CH2:14][CH2:15][CH:16]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)[CH2:17][CH2:18]2)=[N:6][C:5]2[C:9]1=[N:10][C:2]([C:39]1[C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[C:42]([NH2:49])=[N:41][CH:40]=1)=[N:3][C:4]=2[N:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1

Komponenten

9

Edukt 3

HCID 10340Sodium CarbonateHCID 596034954-(1-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methyl)piperidin-4-yl)morpholineHCID 674926724-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1-amine

Produkt 1

HCID 596055944-(9-methyl-6-morpholino-8-((4-morpholinopiperidin-1-yl)methyl)-9H-purin-2-yl)isoquinolin-1-amineAusbeute 14 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 702EthanolLösungsmittelHCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a degassed suspension of 4-(1-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methyl)piperidin-4-yl)morpholine (84 mg, 0.19 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1-amine (52 mg, 0.19 mmol), 2 M Na2CO3 aqueous solution (0.19 mL, 0.38 mmol) in toluene (3 mL) and ethanol (1 mL) was added Pd(PPh3)4 (11 mg, 0.010 mmol). The suspension was then stirred under nitrogen at 100° C. for 18 hours. The reaction mixture was then diluted with EtOAc and water. The aqueous layer was extracted three times with EtOAc. The combined organic extracts were washed with water, dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography (25% MeOH in DCM) to give 139 as a white solid (14.3 mg, 14%). LCMS: M+H+=544.3. 1H-NMR (400 MHz, DMSO-d6): δ 9.01 (d, 1H), 8.25 (d, 1H), 8.16 (s, 1H), 7.67 (t, 1H), 7.49 (t, 1H), 7.08 (s, 2H), 4.23 (s, br, 4H), 3.82 (s, 3H), 3.78 (m, 6H), 3.55 (m, 4H), 2.88 (m, 2H), 2.43 (m, 4H), 2.07 (m, 3H), 1.75 (m, 2H), 1.38 (m, 2H)

Aufarbeitung

  1. extractionThe aqueous layer was extracted three times with EtOAc
  2. washThe combined organic extracts were washed with water
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography (25% MeOH in DCM)

Quellen und Nachweise

ORD-Eintrag
ord-609e2eddce9e48c285c5981da2430e8a
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08394796B2

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