Potassium Phosphate, Tribasic → 5-(5-(benzyloxy)-6-(3-(hydroxymethyl)pyrazolo[1,5-a]pyridin-2-yl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide

HRID 1776900Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1776900
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[C:19]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:24])=[O:23])[C:18](C4C=CC=C(B5OC(C)(C)C(C)(C)O5)C=4)=[CH:17][C:11]=3[C:12]=2[C:13]([NH:15][CH3:16])=[O:14])=[CH:4][CH:3]=1.[CH2:42]([O:49][C:50]1[C:51]([C:57]2[C:65]([CH2:66][OH:67])=[C:60]3[CH:61]=[CH:62][CH:63]=[CH:64][N:59]3[N:58]=2)=[N:52][C:53](Cl)=[CH:54][CH:55]=1)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.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]>[CH2:42]([O:49][C:50]1[CH:55]=[CH:54][C:53]([C:18]2[C:19]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:23])=[O:24])=[CH:20][C:10]3[O:9][C:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)=[C:12]([C:13]([NH:15][CH3:16])=[O:14])[C:11]=3[CH:17]=2)=[N:52][C:51]=1[C:57]1[C:65]([CH2:66][OH:67])=[C:60]2[CH:61]=[CH:62][CH:63]=[CH:64][N:59]2[N:58]=1)[C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1

Komponenten

7

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 674032762-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)benzofuran-3-carboxamideHCID 86728284(2-(3-(Benzyloxy)-6-chloropyridin-2-yl)pyrazolo[1,5-a]pyridin-3-yl)methanol

Produkt 1

HCID 712954825-(5-(benzyloxy)-6-(3-(hydroxymethyl)pyrazolo[1,5-a]pyridin-2-yl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamideAusbeute 53 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 218864351,4-Dioxane--water (1/1)Lösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a degassed solution of 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)benzofuran-3-carboxamide (452 mg, 0.90 mmol) and compound (2-(3-(benzyloxy)-6-chloropyridin-2-yl)pyrazolo[1,5-a]pyridin-3-yl)methanol (300 mg, 0.82 mmol) in dioxane/H2O (5 mL/1 mL) was added Pd2(dba)3 (90 mg, 0.1 mmol), X-Phos (95 mg, 0.2 mmol) and K3PO4 (1.2 g, 2.4 mmol) under N2. After stirred at 100° C. overnight, the reaction mixture was cooled to room temperature and filtered. The filtrate was washed with brine and dried over Na2SO4. After concentrated, the resulting residue was purified using column chromatography (petroleum ether:ethyl acetate=1:2) to provide the product of compound 5-(5-(benzyloxy)-6-(3-(hydroxymethyl)pyrazolo[1,5-a]pyridin-2-yl)pyridin-2-yl)-2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)benzofuran-3-carboxamide (300 mg, yield: 53%). 1H-NMR (Methanol-d4, 400 MHz) δ 8.47 (d, J=8.8 Hz, 1H), 8.00 (dd, J=5.2, 8.8 Hz, 2H), 7.76 (d, J=8.8 Hz, 1H), 7.68 (d, J=9.2 Hz, 1H), 7.63 (d, J=8.4 Hz, 1H), 7.30˜7.24 (m, 7H), 7.16˜7.11 (m, 1H), 7.13 (dt, J=0.8, 6.8 Hz, 1H), 5.22 (s, 2H), 4.74 (s, 2H), 3.29 (s, 3H), 2.93 (s, 3H), 2.89 (s, 3H). MS (M+H)+: 706.

Aufarbeitung

  1. temperaturethe reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. washThe filtrate was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationAfter concentrated
  6. customthe resulting residue was purified

Quellen und Nachweise

ORD-Eintrag
ord-2030470ac69844988021883c8fdec586
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09265773B2

Notizen zur Reaktion

Wird geladen…