Cesium carbonate → 3-Chloro-5-fluoro-4-[4-(6-methyl-pyrimidin-4-ylamino)-thiazolo[5,4-c]pyridin-2-yl]-benzonitrile

HRID 2366230Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2366230
Br[C:2]1[C:7]2[S:8][C:9]([C:11]3[C:18]([F:19])=[CH:17][C:14]([C:15]#[N:16])=[CH:13][C:12]=3[Cl:20])=[N:10][C:6]=2[CH:5]=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:27]=[C:26]([CH3:28])[N:25]=[CH:24][N:23]=1.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.C(=O)([O-])[O-].[Cs+].[Cs+]>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]>[Cl:20][C:12]1[CH:13]=[C:14]([CH:17]=[C:18]([F:19])[C:11]=1[C:9]1[S:8][C:7]2[C:2]([NH:21][C:22]3[CH:27]=[C:26]([CH3:28])[N:25]=[CH:24][N:23]=3)=[N:3][CH:4]=[CH:5][C:6]=2[N:10]=1)[C:15]#[N:16]

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 5728526-Methylpyrimidin-4-amineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 867233154-(4-Bromothiazolo[5,4-c]pyridin-2-yl)-3-chloro-5-fluorobenzonitrile

Produkt 1

HCID 569532043-Chloro-5-fluoro-4-[4-(6-methyl-pyrimidin-4-ylamino)-thiazolo[5,4-c]pyridin-2-yl]-benzonitrileAusbeute 37,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

A mixture of 4-(4-bromo-thiazolo[5,4-c]pyridin-2-yl)-3-chloro-5-fluoro-benzonitrile (0.087 g, 0.24 mmol), 4-amino-6-methylpyrimidine (0.024 g, 0.22 mmol), Pd2(dba)3 (0.011 g, 0.01 mmol), XantPhos (0.014 g, 0.02 mmol) and cesium carbonate (0.192 g, 0.59 mmol) in dioxane (2.4 mL) was degassed with nitrogen and heated to 70° C. for 16 hours. The reaction mixture was diluted with DCM and water, and then filtered through Celite®. The layers of the filtrate were separated and the organic layer dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography eluting with 0-5% MeOH in DCM and triturated with acetonitrile to give the desired compound as a yellow solid (0.033 g, 35% yield). 1H NMR (300 MHz, DMSO-d6): δ 10.70 (s, 1H), 8.63 (d, J=1.2 Hz, 1H), 8.46 (d, J=5.6 Hz, 1H), 8.27 (t, J=1.3 Hz, 1H), 8.22 (dd, J=9.0, 1.4 Hz, 1H), 7.85 (d, J=5.6 Hz, 1H), 7.56 (s, 1H), 2.39 (s, 3H). LCMS (Method C): RT=3.30 min, m/z: 397 [M+H+].

Aufarbeitung

  1. customwas degassed with nitrogen
  2. additionThe reaction mixture was diluted with DCM and water
  3. filtrationfiltered through Celite®
  4. customThe layers of the filtrate were separated
  5. dry with materialthe organic layer dried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel flash chromatography
  8. washeluting with 0-5% MeOH in DCM
  9. customtriturated with acetonitrile

Quellen und Nachweise

ORD-Eintrag
ord-a0b80589bd1f4c16a4b77336b4ce1084
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08697708B2

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