Hydrochloric Acid → HCID 76285608, Verbindung

HRID 572037Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 572037
[CH2:1]([O:8][C@H:9]1[CH2:13][N:12]([C:14]([O:16]C(C)(C)C)=O)[C@H:11]([CH2:21]O)[CH2:10]1)[C:2]1C=CC=CC=1.Cl.O1CCOCC1.[OH:30][CH:31]([C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([C:41]([F:44])([F:43])[F:42])[CH:36]=1)[C:32]([OH:34])=O.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)[C:56]2[N:57]=[CH:58][CH:59]=[CH:60][C:55]=2[N:54]=N1.C[N:70]1CCO[CH2:72][CH2:71]1>CO>[CH:60]1([C:55]2[N:54]=[CH:2][C:1]([O:8][C@H:9]3[CH2:13][N:12]4[C:14](=[O:16])[CH2:72][CH2:71][N:70]([C:32](=[O:34])[CH:31]([OH:30])[C:35]5[CH:40]=[CH:39][CH:38]=[C:37]([C:41]([F:44])([F:43])[F:42])[CH:36]=5)[CH2:21][C@@H:11]4[CH2:10]3)=[N:57][CH:56]=2)[CH2:59][CH2:58]1

Komponenten

8

Edukt 6

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 312751,4-DioxaneHCID 101658DL-2-(3-Trifluoromethyl)phenylglycollic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 14821719HCID 14821719, Verbindung

Produkt 1

HCID 76285608HCID 76285608, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

To a solution of the product from Example 28, Part F (90 mg, 0.232 mmol) in anhydrous methanol (3 mL) was added 4 M HCl in 1,4-dioxane (0.579 mL, 2.317 mmol). The resulting mixture was stirred at room temperature for 18 hours, and the volatiles were removed in vacuo. The residue was suspended in N,N-dimethylformamide (3 mL), 2-hydroxy-2-(3-(trifluoromethyl)phenyl)acetic acid (0.056 g, 0.255 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 0.106 g, 0.278 mmol), and N-methyl morpholine (0.117 g, 1.158 mmol) were added, and the resulting solution was stirred at room temperature for 16 hours. The mixture was partitioned between water and ethyl acetate. The organic extract was washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using a solvent gradient of 0-7% methanol in dichloromethane. The title compound was obtained as a colorless solid (0.065 g, 57% yield). 1H NMR (400 MHz, pyridine-d5, 90° C.) δ ppm 8.09-7.99 (m, 2H), 7.98 (d, J=1.4 Hz, 1H), 7.87-7.79 (m, 1H), 7.56 (d, J=1.3 Hz, 1H), 7.43 (t, J=7.8 Hz, 1H), 5.94-5.85 (m, 1H), 5.40 (t, J=4.1 Hz, 1H), 4.90-4.15 (m, 3H), 4.12 (d, J=13.5 Hz, 1H), 3.73 (dd, J=13.5, 4.3 Hz, 1H), 3.50-2.15 (m, 6H), 2.07-1.79 (m, 2H), 1.05-0.93 (m, 2H), 0.95-0.83 (m, 2H).); MS (ESI) m/z 491 (M+H)+.

Aufarbeitung

  1. customthe volatiles were removed in vacuo
  2. stirringthe resulting solution was stirred at room temperature for 16 hours
  3. customThe mixture was partitioned between water and ethyl acetate
  4. extractionThe organic extract
  5. washwas washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by column chromatography on silica gel using a solvent gradient of 0-7% methanol in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-1a0598faff80408692790122d9cbf55f
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09029361B2

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