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

HRID 470188

Reaktionsgleichung

Reaktionsgleichung von HRID 470188
[CH3:1][C:2]1([CH3:12])[O:6][C@@H:5]2[C@@H:7]([CH3:11])[CH2:8][C@H:9](O)[C@@H:4]2[O:3]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:9]3[C@H:4]4[C@H:5]([O:6][C:2]([CH3:12])([CH3:1])[O:3]4)[C@@H:7]([CH3:11])[CH2:8]3)[C:37]=2[C:36]([F:42])=[CH:35][N:34]=1.[F:32][C:33]1[C:38]2[N:39]([C@H:9]3[C@H:4]4[C@H:5]([O:6][C:2]([CH3:12])([CH3:1])[O:3]4)[C@@H:7]([CH3:11])[CH2:8]3)[CH:40]=[N:41][C:37]=2[C:36]([F:42])=[CH:35][N:34]=1

Komponenten

7

Edukt 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 10877589(3aS,4S,6S,6aR)-2,2,6-trimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-olHCID 178506010HCID 178506010, Verbindung

Produkt 2

HCID 583292804,7-difluoro-3-((3aS,4R,6S,6aR)-2,2,6-trimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-3H-imidazo[4,5-c]pyridineHCID 583292964,7-difluoro-1-((3 aS,4R,6S,6aR)-2,2,6-trimethyltetrahydro-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

(3aS,4S,6S,6aR)-2,2,6-trimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-ol (6-2) (400 mg, 2.3 mmol, 1 equiv) was dissolved in THF (25 mL). Triphenylphosphine (914 mg, 3.5 mmol, 1.5 equiv) was added followed by 4,7-difluoro-1H-imidazo[4,5-c]pyridine (1-4) (396 mg, 2.6 mmol, 1.1 equiv). The mixture was cooled to 0° C. and DIAD (0.72 mL, 3.7 mmol, 1.6 equiv) was added dropwise. The resulting mixture was stirred at ambient temperature for 14 hours and then heated to 50° C. for an additional 72 hours. The solvent was removed at reduced pressure and the yellow residue was purified via flash chromatography (40 g SiO2, 15-100% EtOAc in hexanes) to yield 4,7-difluoro-1-((3aS,4R,6S,6aR)-2,2,6-trimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-1H-imidazo[4,5-c]pyridine (6-3) and 4,7-difluoro-3-((3aS,4R,6S,6aR)-2,2,6-trimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-3H-imidazo[4,5-c]pyridine (6-4) as a 1:1 regioisomeric mixture. 1H NMR (6-3) (500 MHz, CDCl3): δ 8.02 (s, 1 H); 7.84 (t, J=4.5 Hz, 1H); 4.80-4.91 (m, 2H); 4.41 (q, J=6.5 Hz, 1H); 2.53 (sextuplet, J=6.5 Hz, 1H); 2.29 (septuplet, J=6.0 Hz, 1H); 2.00 (m, 1H); 1.57 (s, 3H); 1.31 (s, 3H); 1.25 (d, J=6.5 Hz, 3H). LRMS m/z (M+H) 309.9 found, 310.1 required. 1H NMR (6-4) (500 MHz, CDCl3): δ 8.10 (s, 1H); 7.81 (t, J=5.0 Hz, 1H); 4.80-4.91 (m, 2H); 4.41 (q, J=6.5 Hz, 1H); 2.53 (sextuplet, J=6.5 Hz, 1H); 2.29 (septuplet, J=6.0 Hz, 1H); 2.00 (m, 1H); 1.57 (s, 3H); 1.31 (s, 3H); 1.25 (d, J=6.5 Hz, 3H). LRMS m/z (M+H) 309.9 found, 310.1 required.

Aufarbeitung

  1. temperatureheated to 50° C. for an additional 72 hours
  2. customThe solvent was removed at reduced pressure
  3. customthe yellow residue was purified via flash chromatography (40 g SiO2, 15-100% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-3f1811e43d8f405583324d4549c9b81f
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08629275B2

Verknüpfte Notizen

Wird geladen…