Hydrochloric Acid → (2R)-3-[4-{3-[(1S)-1-(2-Chloro-3-fluoro-6-methoxyphenyl)ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-3-(trifluoromethyl)-1H-pyrazol-1-yl]propane-1,2-diol

HRID 2095660Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2095660
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([O:9][CH3:10])[C:3]=1[C@H:11]([C:13]1[C:21]2[C:16](=[N:17][CH:18]=[C:19](B3OC(C)(C)C(C)(C)O3)[CH:20]=2)[NH:15][CH:14]=1)[CH3:12].Br[C:32]1[C:33]([C:45]([F:48])([F:47])[F:46])=[N:34][N:35]([CH2:37][C@@H:38]2[CH2:42][O:41]C(C)(C)[O:39]2)[CH:36]=1.C([O-])([O-])=O.[K+].[K+].O.Cl>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([O:9][CH3:10])[C:3]=1[C@H:11]([C:13]1[C:21]2[C:16](=[N:17][CH:18]=[C:19]([C:32]3[C:33]([C:45]([F:47])([F:48])[F:46])=[N:34][N:35]([CH2:37][C@@H:38]([OH:39])[CH2:42][OH:41])[CH:36]=3)[CH:20]=2)[NH:15][CH:14]=1)[CH3:12]

Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 962Water2×HCID 11430Potassium CarbonateHCID 585160404-bromo-1-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-3-(trifluoromethyl)-1H-pyrazoleHCID 670040713-[(S)-1-(2-chloro-3-fluoro-6-methoxyphenyl)-ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine

Produkt 1

HCID 54674981(2R)-3-[4-{3-[(1S)-1-(2-Chloro-3-fluoro-6-methoxyphenyl)ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-3-(trifluoromethyl)-1H-pyrazol-1-yl]propane-1,2-diol

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
45 °C

Versuchsvorschrift

A mixture of 3-[(S)-1-(2-chloro-3-fluoro-6-methoxyphenyl)-ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (10.0 mg, 0.0232 mmol), 4-bromo-1-{[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-3-(trifluoromethyl)-1H-pyrazole (15.3 mg, 0.0464 mmol), Pd(PPh3)4 (1.34 mg, 0.00116 mmol), K2CO3 (9.63 mg, 0.0696 mmol) and 4:1 dioxane:H2O (0.5 mL, 5 mmol) was heated in a microwave reactor at 95° C. for 20 min. 12 M of HCl in H2O (0.1 mL, 1 mmol) was added, and the solution was heated to 45° C. for 1 h. The solution was used directly for HPLC purification, and the fractions containing the pure product were concentrated in vacuo to afford the title compound as a white solid. 1H NMR (400 MHz, CD3OD): δ=1.79 (d, J=7.1 Hz, 3H), 3.56 (d, J=5.3 Hz, 2H), 3.63 (br. s., 3H), 4.04 (dd, J=8.1, 3.8 Hz, 1H), 4.19 (dd, J=13.9, 8.1 Hz, 1H), 4.38 (dd, J=13.9, 3.8 Hz, 1H), 5.10 (q, J=7.0 Hz, 1H), 6.87 (dd, J=9.0, 4.2 Hz, 1H), 7.06 (t, J=8.8 Hz, 1H), 7.35 (d, J=1.3 Hz, 1H), 7.54 (s, 1H), 7.82 (s, 1H), 8.13 (br. s., 1H). MS (ES+): m/z=513.06/515.06 (100/50) [MH+]. HPLC: tR=3.26 min (polar—5 min, ZQ3).

Aufarbeitung

  1. customThe solution was used directly for HPLC purification
  2. additionthe fractions containing the pure product
  3. concentrationwere concentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-a5542beae4734f9b94b8fad71fe2f0e9
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08445510B2

Notizen zur Reaktion

Wird geladen…