Hydrochloric Acid → Hydrochloric Acid

HRID 1522621Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1522621
[Cl:1][C:2]1[C:3]2[C:4](=[CH:9][N:10]([CH2:12][CH2:13][O:14]C3CCCCO3)[N:11]=2)[N:5]=[CH:6][C:7]=1[F:8].ClC1C(F)=CN=C2C=NN(CCOC3CCCCO3)C=12.[F:41][C:42]1[C:43]([C:49]2[CH:54]=[C:53]([NH2:55])[C:52]([CH3:56])=[CH:51][N:50]=2)=[N:44][C:45]([CH3:48])=[CH:46][CH:47]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[K+].[K+].Cl>CC(O)(C)C>[F:8][C:7]1[CH:6]=[N:5][C:4]2=[CH:9][N:10]([CH2:12][CH2:13][OH:14])[N:11]=[C:3]2[C:2]=1[NH:55][C:53]1[C:52]([CH3:56])=[CH:51][N:50]=[C:49]([C:43]2[C:42]([F:41])=[CH:47][CH:46]=[C:45]([CH3:48])[N:44]=2)[CH:54]=1.[ClH:1]

Komponenten

9

Edukt 6

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 674696167-chloro-6-fluoro-2-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-2H-pyrazolo[4,3-b]pyridineHCID 674696193'-Fluoro-5,6'-dimethyl-2,2'-bipyridin-4-amineHCID 674704897-chloro-6-fluoro-1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-pyrazolo[4,3-b]pyridine

Produkt 2

HCID 313Hydrochloric AcidHCID 682126902-(6-fluoro-7-(3'-fluoro-5,6'-dimethyl-2,2'-bipyridin-4-ylamino)-2H-pyrazolo[4,3-b]pyridin-2-yl)ethanol

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6386tert-ButanolLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To 7-chloro-6-fluoro-2-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-2H-pyrazolo[4,3-b]pyridine (85 mg, 0.284 mmol) and 7-chloro-6-fluoro-1-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-pyrazolo[4,3-b]pyridine (85 mg, 0.284 mmol) in t-BuOH (4 mL) was added 3′-fluoro-5,6′-dimethyl-2,2′-bipyridin-4-amine (185 mg, 0.851 mmol), tri(dibenzylidene acetone)dipalladium(0) (26.0 mg, 0.028 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (27.0 mg, 0.057 mmol) and potassium carbonate (157 mg, 1.134 mmol) and the mixture was heated at 100° C. over night. The mixture was cooled and evaporated to give a residue which was partitioned between EtOAc (75 mL) and water. The layers were separated and the aqueous layer was extracted with EtOAc (75 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated to give a residue which was purified on HPLC using a gradient of 20-50% acetonitrile (containing 0.035% TFA) in water (containing 0.05% TFA) using a Sunfire Prep 5 μm C18, 75×30 mm column to give a residue. The residue was combined with 1N HCl (3 mL) and the solution was stirred for an hour, evaporated and lyophilized to give the title compound as a HCl salt. 1HNMR (400 MHz, DMSO-d6) δ ppm 2.52 (s, 3H) 2.58 (s, 3H) 3.80 (t, J=5.43 Hz, 2H) 4.47 (t, J=5.43 Hz, 2H) 7.28 (d, J=1.77 Hz, 1H) 7.57 (dd, J=8.59, 3.54 Hz, 1H) 7.82 (dd, J=11.37, 8.59 Hz, 1H) 8.52 (s, 1H) 8.74 (d, J=2.78 Hz, 1H) 8.87 (s, 1H) 10.16 (br. s., 1H). MS [M+H] found 397.4.

Aufarbeitung

  1. temperatureThe mixture was cooled
  2. customevaporated
  3. customto give a residue which
  4. customwas partitioned between EtOAc (75 mL) and water
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with EtOAc (75 mL)
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give a residue which
  11. customwas purified on HPLC
  12. customto give a residue
  13. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-02df48069d774fb8b7e757a357c98c84
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09073918B2

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