Dimethylformamide → 7-bromo-8-fluoro-3-((3-methyloxetan-3-yl)ethynyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

HRID 335874Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 335874
[Br:1][C:2]1[CH:3]=[C:4]2[C:16]3([CH2:20][O:19][C:18]([NH2:21])=[N:17]3)[C:15]3[C:10](=[N:11][CH:12]=[C:13](I)[CH:14]=3)[O:9][C:5]2=[CH:6][C:7]=1[F:8].C[Si](C)(C)[C:25]#[C:26][C:27]1([CH3:31])[CH2:30][O:29][CH2:28]1.CN(C=O)C>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.[Cu]I.O>[Br:1][C:2]1[CH:3]=[C:4]2[C:16]3([CH2:20][O:19][C:18]([NH2:21])=[N:17]3)[C:15]3[C:10](=[N:11][CH:12]=[C:13]([C:25]#[C:26][C:27]4([CH3:31])[CH2:30][O:29][CH2:28]4)[CH:14]=3)[O:9][C:5]2=[CH:6][C:7]=1[F:8]

Komponenten

7

Edukt 3

HCID 6228DimethylformamideHCID 58547788Trimethyl((3-methyloxetan-3-yl)ethynyl)silaneHCID 673830077-bromo-8-fluoro-3-iodo-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

Produkt 1

HCID 673834197-bromo-8-fluoro-3-((3-methyloxetan-3-yl)ethynyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amineAusbeute 42,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Katalysator2×HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittel

Versuchsvorschrift

A vial charged with Pd(PPh3)4 (0.73 g, 0.63 mmol), copper(I) iodide (0.48 g, 2.52 mmol), 7-bromo-8-fluoro-3-iodo-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (3.0 g, 6.30 mmol), trimethyl((3-methyloxetan-3-yl)ethynyl)silane (1.06 g, 6.30 mmol) and 13 mL DMF was degassed with argon and treated with DIPA (4.49 mL, 31.5 mmol). The resulting slurry was allowed to stir at RT for 18 h at which point an additional portion of copper(I) iodide (0.48 g, 2.52 mmol) was added. After stirring for an additional 4 h the reaction mixture was poured into water (50 mL) and was extracted with EtOAc (3×100 mL). The resulting suspension was filtered through a glass frit and the filtrate was dried over MgSO4 and concentrated in vacuo. Purification of the crude residue by column chromatography [0-50% (9:1 CH2Cl2:MeOH)/CH2Cl2] provided 7-bromo-8-fluoro-3-((3-methyloxetan-3-yl)ethynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (1.18 g, 2.66 mmol).

Aufarbeitung

  1. customwas degassed with argon
  2. additiontreated with DIPA (4.49 mL, 31.5 mmol)
  3. additionwas added
  4. extractionwas extracted with EtOAc (3×100 mL)
  5. filtrationThe resulting suspension was filtered through a glass frit
  6. dry with materialthe filtrate was dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customPurification of the crude residue by column chromatography [0-50% (9:1 CH2Cl2:MeOH)/CH2Cl2]

Quellen und Nachweise

ORD-Eintrag
ord-fef6a496d496400382c537e8b352a097
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08883782B2

Notizen zur Reaktion

Wird geladen…