Formaldehyde → 4-{4-Chloro-2-[1-(1-methylazetidin-3-yl)-1H-pyrazol-5-yl]phenoxy}-2,5-difluoro-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide

HRID 1692219

Reaktionsgleichung

Reaktionsgleichung von HRID 1692219
[NH:1]1[CH2:4][CH:3]([N:5]2[C:9]([C:10]3[CH:33]=[C:32]([Cl:34])[CH:31]=[CH:30][C:11]=3[O:12][C:13]3[C:18]([F:19])=[CH:17][C:16]([S:20]([NH:23][C:24]4[S:28][N:27]=[CH:26][N:25]=4)(=[O:22])=[O:21])=[C:15]([F:29])[CH:14]=3)=[CH:8][CH:7]=[N:6]2)[CH2:2]1.Cl[CH2:36]Cl.C=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(C(C)=O)C(C)C.C(O)(=O)C.O.C(OCC)(=O)C>[Cl:34][C:32]1[CH:31]=[CH:30][C:11]([O:12][C:13]2[C:18]([F:19])=[CH:17][C:16]([S:20]([NH:23][C:24]3[S:28][N:27]=[CH:26][N:25]=3)(=[O:21])=[O:22])=[C:15]([F:29])[CH:14]=2)=[C:10]([C:9]2[N:5]([CH:3]3[CH2:2][N:1]([CH3:36])[CH2:4]3)[N:6]=[CH:7][CH:8]=2)[CH:33]=1

Komponenten

7

Edukt 4

HCID 712Formaldehyde2×HCID 6344DichloromethaneHCID 5049666Sodium triacetoxyborohydride2×HCID 46841215NaV1.7 Blocker-801

Produkt 1

HCID 468414994-{4-Chloro-2-[1-(1-methylazetidin-3-yl)-1H-pyrazol-5-yl]phenoxy}-2,5-difluoro-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8857Ethyl AcetateLösungsmittelHCID 86643822Methyl isobutyl ketone acetic acid waterLösungsmittel

Versuchsvorschrift

4-[2-(1-azetidin-3-yl-1H-pyrazol-5-yl)-4-chlorophenoxy]-2,5-difluoro-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide (Example 801, 54 mg, 0.1 mmol) was stirred with dichloromethane (2 mL) methanol (0.2 mL) and 37% w/v aqueous formaldehyde solution (0.025 mL, 0.34 mmol) at room temperature for 15 minutes. Sodium triacetoxyborohydride (68 mg, 0.32 mmol) was added at the reaction stirred at room temperature for 18 hours. 37% wt/vol aqueous formaldehyde solution (0.025 mL, 0.34 mmol) was added and the reaction stirred for 15 minutes then sodium triacetoxyborohydride (68 mg, 0.32 mmol) was added at the reaction stirred at room temperature for 3 hours. The mixture was evaporated and the residue dissolved in ethyl acetate (20 mL) and washed with saturated aqueous sodium bicarbonate solution (2×10 ml) and saturated aqueous sodium chloride solution (2×10 ml). The organic layer was separated, dried over sodium sulphate, filtered and evaporated to give a solid. The solid was suspended in methyl isobutyl ketone:acetic acid:water 2:1:1 and eluted through a silica column (5 g) with methyl isobutyl ketone:acetic acid:water 2:1:1. The appropriate fractions were combined and concentrated in vacuo to give a film. This was scratched with ethyl acetate then diethyl ether and dried in vacuo to give the title compound as a white solid. Yield 30 mg. 54%.

Aufarbeitung

  1. customat room temperature
  2. customfor 15 minutes
  3. stirringthe reaction stirred for 15 minutes
  4. stirringstirred at room temperature for 3 hours
  5. customThe mixture was evaporated
  6. dissolutionthe residue dissolved in ethyl acetate (20 mL)
  7. washwashed with saturated aqueous sodium bicarbonate solution (2×10 ml) and saturated aqueous sodium chloride solution (2×10 ml)
  8. customThe organic layer was separated
  9. dry with materialdried over sodium sulphate
  10. filtrationfiltered
  11. customevaporated
  12. customto give a solid
  13. washeluted through a silica column (5 g) with methyl isobutyl ketone:acetic acid:water 2:1:1
  14. concentrationconcentrated in vacuo
  15. customto give a film
  16. dry with materialdiethyl ether and dried in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-a4e33e4941d146d5ba9860d36e823ad7
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08153814B2

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