Cesium carbonate → N-(3-(6-((3-fluoro-4-morpholinophenyl)amino)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)acrylamide

HRID 1500791Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1500791
Cl[C:2]1[N:7]=[C:6]2[N:8]([CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][O:12]3)[N:9]=[CH:10][C:5]2=[C:4]([C:17]2[CH:18]=[C:19]([NH:23][C:24](=[O:27])[CH:25]=[CH2:26])[CH:20]=[CH:21][CH:22]=2)[N:3]=1.[F:28][C:29]1[CH:30]=[C:31]([CH:33]=[CH:34][C:35]=1[N:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1)[NH2:32].C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:28][C:29]1[CH:30]=[C:31]([NH:32][C:2]2[N:7]=[C:6]3[N:8]([CH:11]4[CH2:16][CH2:15][CH2:14][CH2:13][O:12]4)[N:9]=[CH:10][C:5]3=[C:4]([C:17]3[CH:18]=[C:19]([NH:23][C:24](=[O:27])[CH:25]=[CH2:26])[CH:20]=[CH:21][CH:22]=3)[N:3]=2)[CH:33]=[CH:34][C:35]=1[N:36]1[CH2:37][CH2:38][O:39][CH2:40][CH2:41]1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 14853303-Fluoro-4-morpholinoanilineHCID 86677518N-(3-(6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)acrylamide

Produkt 1

HCID 68388393N-(3-(6-((3-fluoro-4-morpholinophenyl)amino)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)acrylamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
200 °C

Versuchsvorschrift

N-(3-(6-Chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)acrylamide (50 mg, 0.130 mmol), 3-fluoro-4-morpholinoaniline (23.00 mg, 0.117 mmol) and Cs2CO3 (50.9 mg, 0.156 mmol) were dissolved in toluene (5 mL) in a sealable microwave compatible reaction tube, then Pd2(dba)3 (2.386 mg, 2.61 μmol) and Xantphos (3.01 mg, 5.21 μmol) were added. The reaction tube was sealed and the reaction was heated under microwave irradiation (60 min, 200° C., 3 atm). Reaction progress was monitored by TLC. After completion of the reaction, the solvent was removed by vacuum and compound was purified by column chromatography. 1H NMR (400 MHz, CD3OD): δ 8.64 (s, 1H), 8.26 (s, 1H), 7.92 (d, 1H, J=7.6 Hz), 7.82 (dd, 1H, J=2.4 and 15.2 Hz), 7.68 (m, 1H), 7.48 (t, 1H, J=7.6 Hz), 7.35 (dd, 1H, J=1.6 and 8.8 Hz), 6.95 (t, 1H, J=8.8 Hz), 6.43 (m, 2H), 5.87 (dd, 1H, J=2.4 and 10.4 Hz), 5.80 (dd, 1H, J=2.8 and 8.8 Hz), 4.11 (m, 1H), 3.82 (m, 4H), 3.75 (m, 1H), 3.00 (m, 4H), 2.60 (m, 1H), 2.13 (m, 1H), 1.97 (m, 1H), 1.83-1.73 (m, 3H); ESI-MS: [M+H]+.

Aufarbeitung

  1. customThe reaction tube was sealed
  2. customReaction progress
  3. customAfter completion of the reaction
  4. customthe solvent was removed by vacuum and compound
  5. customwas purified by column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-2fce41c9f5754deb9bfd45af4072096c
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09206176B2

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