Diisopropylethylamine → (2S,4R)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-cyano-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide

HRID 1630082

Reaktionsgleichung

Reaktionsgleichung von HRID 1630082
[C:1]([C@H:3]1[CH2:7][NH:6][C@H:5]([C:8]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)=[CH:13][CH:12]=2)=[O:9])[CH2:4]1)#[N:2].[N:25]1([CH2:30][C:31](O)=[O:32])[CH:29]=[N:28][CH:27]=[N:26]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[N:25]1([CH2:30][C:31]([N:6]2[CH2:7][C@H:3]([C:1]#[N:2])[CH2:4][C@H:5]2[C:8]([NH:10][C:11]2[CH:12]=[CH:13][C:14]([O:17][C:18]3[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=3)=[CH:15][CH:16]=2)=[O:9])=[O:32])[CH:29]=[N:28][CH:27]=[N:26]1

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 18101801,2,4-Triazole-1-acetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67010040(2S,4R)-4-cyano-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide

Produkt 1

HCID 67010058(2S,4R)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-cyano-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamideAusbeute 62 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A flask was charged with (2S,4R)-4-cyano-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide (0.88 g, 2.69 mmol), prepared as in Reference 8, 2-(1H-1,2,4-triazol-1-yl)acetic acid (340 mg, 2.69 mmol), DIEA (3.0 mL, 17 mmol), HATU (1.12 g, 2.96 mmol) and DMF (10 mL). The reaction mixture was stirred at ambient temperature for 20 minutes and then quenched with saturated sodium bicarbonate (aq., 10 mL). The mixture was ethyl acetate (20 mL) and the extract was washed with deionized water (10 mL) and then brine (10 mL), dried over anhydrous sodium sulfate, filtered and concentrated. Product was purified from the residue by chromatography (EtOAc to EtOAc/MeOH (9:1)+1% NEt3) to give (2S,4R)-1-(2-(1H-1,2,4-triazol-1-yl)acetyl)-4-cyano-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide (0.72 g, 1.66 mmol, 62% yield) as an off-white solid. 1H-NMR (400 MHz, DMSO-d6): 10.20 (s, 1H), 8.46 (s, 1H), 7.97 (s, 1H), 7.57 (d, J=8.8 Hz, 2H), 7.22-7.17 (m, 2H), 7.03-6.95 (m, 4H), 5.38-5.26 (m, 2H), 4.59-4.55 (m, 1H), 4.08-3.94 (m, 2H), 3.84-3.50 (m, 2H), 2.39-2.32 (m, 1H). MS (EI) for C22H19FN6O3. found 517.3 (MH+).

Aufarbeitung

  1. customquenched with saturated sodium bicarbonate (aq., 10 mL)
  2. washthe extract was washed with deionized water (10 mL)
  3. dry with materialbrine (10 mL), dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customProduct was purified from the residue by chromatography (EtOAc to EtOAc/MeOH (9:1)+1% NEt3)

Quellen und Nachweise

ORD-Eintrag
ord-b0fac0cb0e92469aa3634e706aa48003
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08791102B2

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