Sodium Iodide → 6-chloro-3-(2,2-difluoro-1-methylcyclopropyl)-1-trityl-1H-pyrazolo[4,3-c]pyridine

HRID 571409Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 571409
[Na+].[I-].[Cl:3][C:4]1[N:9]=[CH:8][C:7]2[C:10]([C:32]([CH3:34])=[CH2:33])=[N:11][N:12]([C:13]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:6]=2[CH:5]=1.[F:35][C:36]([Si](C)(C)C)([F:38])F>C1COCC1>[Cl:3][C:4]1[N:9]=[CH:8][C:7]2[C:10]([C:32]3([CH3:34])[CH2:33][C:36]3([F:38])[F:35])=[N:11][N:12]([C:13]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:6]=2[CH:5]=1

Komponenten

5

Edukt 3

HCID 5238Sodium Iodide2×HCID 552549(Trifluoromethyl)trimethylsilane2×HCID 895259366-chloro-3-(prop-1-en-2-yl)-1-trityl-1H-pyrazolo[4,3-c]pyridine

Produkt 1

HCID 1176008406-chloro-3-(2,2-difluoro-1-methylcyclopropyl)-1-trityl-1H-pyrazolo[4,3-c]pyridineAusbeute 107 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

Reference: Angew. Chemie Int. Ed., 2011, 50(31), 7153. To a 2 dram pressure vial charged with a magnetic stir bar was added anhydrous NaI (3.4 mg, 0.023 mmol), THF (1 ml), and 6-chloro-3-(prop-1-en-2-yl)-1-trityl-1H-pyrazolo[4,3-c]pyridine (50 mg, 0.115 mmol) under nitrogen. To this was added (trifluoromethyl)trimethylsilane (0.042 ml, 0.287 mmol). The reaction vessel was sealed and heated to 65° C. in an oil bath for a period of 2.5 hours. LCMS and TLC indicated product and remaining starting material. Additional sodium iodide (3.4 mg, 0.023 mmol) and (trifluoromethyl)-trimethylsilane (0.042 ml, 0.287 mmol) were added and the reaction was heated overnight at 65° C. The reaction mixture was concentrated and taken up in ether (15 ml). The organic layer was washed with water (15 ml), saturated sodium thiosulfate solution (15 ml), saturated sodium bicarbonate solution (15 ml), and water (15 ml), in that order. The ethereal layer dried over anhydrous magnesium sulfate, concentrated, and purified (12 g silica gel, eluting with 0-10% tOAc/hexanes) to give 6-chloro-3-(2,2-difluoro-1-methylcyclopropyl)-1-trityl-1H-pyrazolo[4,3-c]pyridine (60 mg, 0.123 mmol) as a beige foam. MS ESI calc'd. for C29H22ClF2N3[M+1]+ 486, found 486.

Aufarbeitung

  1. additionTo a 2 dram pressure vial charged with a magnetic stir bar
  2. customThe reaction vessel was sealed
  3. temperaturethe reaction was heated overnight at 65° C
  4. concentrationThe reaction mixture was concentrated
  5. washThe organic layer was washed with water (15 ml), saturated sodium thiosulfate solution (15 ml), saturated sodium bicarbonate solution (15 ml), and water (15 ml), in that order
  6. dry with materialThe ethereal layer dried over anhydrous magnesium sulfate
  7. concentrationconcentrated
  8. custompurified
  9. wash(12 g silica gel, eluting with 0-10% tOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-38acbb2ae10d40499cd011a554ecc333
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09023865B2

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