2-Methyltetrahydrofuran → (R)-methyl 3-((5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-4,4-dimethylpentanoate

HRID 1055038Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1055038
CC1OCCC1.[F:7][C:8]1[CH:9]=[C:10]2[C:16](B3OC(C)(C)C(C)(C)O3)=[CH:15][N:14]([S:26]([C:29]3[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=3)(=[O:28])=[O:27])[C:11]2=[N:12][CH:13]=1.Cl[C:37]1[N:42]=[C:41]([NH:43][C@@H:44]([C:50]([CH3:53])([CH3:52])[CH3:51])[CH2:45][C:46]([O:48][CH3:49])=[O:47])[C:40]([F:54])=[CH:39][N:38]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>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].O>[F:54][C:40]1[C:41]([NH:43][C@@H:44]([C:50]([CH3:53])([CH3:52])[CH3:51])[CH2:45][C:46]([O:48][CH3:49])=[O:47])=[N:42][C:37]([C:16]2[C:10]3[C:11](=[N:12][CH:13]=[C:8]([F:7])[CH:9]=3)[N:14]([S:26]([C:29]3[CH:30]=[CH:31][C:32]([CH3:35])=[CH:33][CH:34]=3)(=[O:28])=[O:27])[CH:15]=2)=[N:38][CH:39]=1

Komponenten

8

Edukt 5

HCID 73012-MethyltetrahydrofuranHCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 672856905-fluoro-1-((4-methylphenyl)sulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo(2,3-b)pyridineHCID 86714731methyl (3R)-3-[(2-chloro-5-fluoropyrimidin-4-yl)amino]-4,4-dimethylpentanoate

Produkt 1

HCID 71247937(R)-methyl 3-((5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-4,4-dimethylpentanoate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
115 °C

Versuchsvorschrift

A 2-MeTHF (253 mL)/water (56 mL) solution of 5-fluoro-1-(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridine, 7a, (24.3 g, 58.3 mmol), methyl (R)-methyl 3-((2-chloro-5-fluoropyrimidin-4-yl)amino)-4,4-dimethylpentanoate, 6a, (14.1 g, 48.6 mmol) and K3PO4 (30.9 g, 146 mmol) was purged with nitrogen for 0.75 h. XPhos (2.8 g, 5.8 mmol) and Pd2(dba)3 (1.1 g, 1.2 mmol) were added and the reaction mixture was stirred at 115° C. in a sealed tube for 2 h. The reaction mixture was cooled and the aqueous phase was removed. The organic phase was filtered through a pad of Celite and the mixture was concentrated to dryness. The residue was purified on silica gel (EA/Hex) to provide the desired product, 8a, (23.2 g): LCMS Gradient 10-90%, 0.1% formic acid, 5 min, C18/ACN, RT=2.18 minutes (M+H) 245.28.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled
  2. customthe aqueous phase was removed
  3. filtrationThe organic phase was filtered through a pad of Celite
  4. concentrationthe mixture was concentrated to dryness
  5. customThe residue was purified on silica gel (EA/Hex)

Quellen und Nachweise

ORD-Eintrag
ord-bb683614ef9e429d9cbdb471afd7169a
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09394302B2

Notizen zur Reaktion

Wird geladen…