Hydrochloric Acid → (2R)-2-(2-(1-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yloxy)propanamide

HRID 1498547Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1498547
C([O:3][C:4](=O)[C@H:5]([O:7][C:8]1[CH:31]=[CH:30][C:11]2[C:12]3[N:16]([CH2:17][CH2:18][O:19][C:10]=2[CH:9]=1)[CH:15]=[C:14]([C:20]1[N:21]([CH2:25][C:26]([F:29])([F:28])[F:27])[N:22]=[CH:23][N:24]=1)[N:13]=3)[CH3:6])C.O.[OH-].[Li+].Cl.C[N:38](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl-].[NH4+].C(N(CC)CC)C>CO.O>[F:27][C:26]([F:29])([F:28])[CH2:25][N:21]1[C:20]([C:14]2[N:13]=[C:12]3[C:11]4[CH:30]=[CH:31][C:8]([O:7][C@H:5]([CH3:6])[C:4]([NH2:38])=[O:3])=[CH:9][C:10]=4[O:19][CH2:18][CH2:17][N:16]3[CH:15]=2)=[N:24][CH:23]=[N:22]1

Komponenten

9

Edukt 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 168937Lithium hydroxide, monohydrateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67050759(R)-2-{2-[2-(2,2,2-Trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yloxy}-propionic acid ethyl ester

Produkt 1

HCID 58204941(2R)-2-(2-(1-(2,2,2-trifluoroethyl)-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yloxy)propanamideAusbeute 40 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittel

Versuchsvorschrift

To a solution (R)-2-{2-[2-(2,2,2-trifluoro-ethyl)-2H-[1,2,4]triazol-3-yl]-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yloxy}-propionic acid ethyl ester in methanol (3 mL) was added water (1 mL) and lithium hydroxide monohydrate (11 mg, 0.42 mmol). The reaction mixture was stirred at RT for 16 h then HCl (1N, aq.) added until pH˜4. The reaction mixture was concentrated in vacuo. The resultant residue was dissolved in DMF (3 mL) and HATU (217 mg, 0.56 mmol), ammonium chloride (45 mg, 0.85 mmol) and triethylamine (119 μL, 0.85 mmol) added. The reaction mixture was stirred at RT for 1 h before being concentrated in vacuo. The residue was dissolved in ethyl acetate (10 mL) and the mixture washed with water, extracting with ethyl acetate (3×10 mL). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0-10% methanol in ethyl acetate) to give 487 as a white solid (49 mg, 40%). LCMS: RT=3.52 min, [M+H]+=423; 1H NMR (400 MHz, d6-DMSO) 8.22 (1H, d, J=8.9 Hz), 8.03 (1H, s), 7.95 (1H, s), 7.51 (1H, br s), 7.22 (1H, br s), 6.73 (1H, dd, J=8.9, 2.6 Hz), 6.50 (1H, d, J=2.6 Hz), 5.86 (2H, q, J=8.9 Hz), 4.64 (1H, q, J=6.6 Hz), 4.51-4.38 (4H, m), 1.40 (3H, d, J=6.4 Hz)

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionThe resultant residue was dissolved in DMF (3 mL)
  3. stirringThe reaction mixture was stirred at RT for 1 h
  4. concentrationbefore being concentrated in vacuo
  5. dissolutionThe residue was dissolved in ethyl acetate (10 mL)
  6. washthe mixture washed with water
  7. extractionextracting with ethyl acetate (3×10 mL)
  8. washThe combined organic extracts were washed with brine
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-23c50dac44904bd98b0ee77393d21f7c
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09198918B2

Notizen zur Reaktion

Wird geladen…