Triphenylphosphine → 4,7-difluoro-3-((3aS,4S,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-3H-imidazo[4,5-c]pyridine

HRID 470182

Reaktionsgleichung

Reaktionsgleichung von HRID 470182
[F:1][C:2]1[C@H:3](O)[C@@H:4]2[O:8][C:7]([CH3:10])([CH3:9])[O:6][C@@H:5]2[CH:11]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:32][C:33]1[C:38]2[N:39]=[CH:40][NH:41][C:37]=2[C:36]([F:42])=[CH:35][N:34]=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[F:32][C:33]1[C:38]2[N:39]=[CH:40][N:41]([C@H:3]3[C@H:4]4[C@H:5]([O:6][C:7]([CH3:10])([CH3:9])[O:8]4)[CH:11]=[C:2]3[F:1])[C:37]=2[C:36]([F:42])=[CH:35][N:34]=1.[F:32][C:33]1[C:38]2[N:39]([C@H:3]3[C@H:4]4[C@H:5]([O:6][C:7]([CH3:10])([CH3:9])[O:8]4)[CH:11]=[C:2]3[F:1])[CH:40]=[N:41][C:37]=2[C:36]([F:42])=[CH:35][N:34]=1

Komponenten

7

Edukt 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 58329271(3aS,4R,6aR)-5-Fluoro-2,2-dimethyl-3a,6a-dihydro-4H-cyclopenta[d][1,3]dioxol-4-olHCID 178506010HCID 178506010, Verbindung

Produkt 2

HCID 583293054,7-difluoro-3-((3aS,4S,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-3H-imidazo[4,5-c]pyridineHCID 583293104,7-difluoro-1-((3aS,4S,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-1H-imidazo[4,5-c]pyridine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

(3S,4R,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-ol (5-6) (290 mg, 1.6 mmol, 1 equiv) was dissolved in dry THF (15 mL). Triphenylphosphine (620 mg, 2.4 mmol, 1.5 equiv) was added followed by 4,7-difluoro-1H-imidazo[4,5-c]pyridine (1-4) (370 mg, 2.4 mmol, 1.5 equiv). The mixture was cooled to 0° C. and DIAD (0.46 mL, 2.4 mmol, 1.5 equiv) was added dropwise. The resulting mixture was stirred at ambient temperature for 2 hours. Upon disappearance of the starting material, the solvent was removed at reduced pressure and the yellow residue was purified by flash chromatography (40 g SiO2, 15-100% EtOAc in hexanes) to yield 4,7-difluoro-1-(3aS,4S,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-1H-imidazo[4,5-c]pyridine (5-7) and 4,7-difluoro-3-((3aS,4S,6aR)-5-fluoro-2,2-dimethyl-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-3H-imidazo[4,5-c]pyridine (5-8) as a 1:1 regioisomeric mixture. 1H NMR (5-7) (500 MHz, CDCl3): δ 7.91 (s, 1H); 7.86 (t, J=2.0 Hz, 1H); 5.80 (s, 1H); 5.66 (s, 1H); 5.38 (m, 1H); 4.75 (q, J=5 Hz, 1H); 1.56 (s, 3H); 1.37 (s, 3H). LRMS m/z (M+H) 311.9 found, 312.1 required. 1H NMR (5-8) (500 MHz, CDCl3): δ 7.99 (s, 1H); 7.89 (t, J=2.0 Hz, 1H); 5.80 (s, 1H); 5.66 (s, 1H); 5.38 (m, 1H); 4.75 (q, J=5 Hz, 1H); 1.56 (s, 3H); 1.37 (s, 3H). LRMS m/z (M+H) 311.9 found, 312.1 required.

Aufarbeitung

  1. customUpon disappearance of the starting material, the solvent was removed at reduced pressure
  2. customthe yellow residue was purified by flash chromatography (40 g SiO2, 15-100% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-279586d6c6994506aaa0df3832c34676
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08629275B2

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