1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → 6-(cis-2-Amino-3,3-difluorocyclohexylamino)-2-(2,4-dimethoxybenzyl)-7-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one

HRID 2092832Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2092832
[NH2:1][C@H:2]1[C:7]([F:9])([F:8])[CH2:6][CH2:5][CH2:4][C@H:3]1[NH:10][C:11]1[N:16]=[C:15](Cl)[C:14]2[C:18](=[O:32])[N:19]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:23]=3[O:30][CH3:31])[CH2:20][C:13]=2[C:12]=1[F:33].[CH3:34][N:35]1[CH:39]=[C:38](B2OC(C)(C)C(C)(C)O2)[CH:37]=[N:36]1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.COCCOC>[NH2:1][C@H:2]1[C:7]([F:9])([F:8])[CH2:6][CH2:5][CH2:4][C@H:3]1[NH:10][C:11]1[N:16]=[C:15]([C:38]2[CH:37]=[N:36][N:35]([CH3:34])[CH:39]=2)[C:14]2[C:18](=[O:32])[N:19]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:23]=3[O:30][CH3:31])[CH2:20][C:13]=2[C:12]=1[F:33]

Komponenten

5

Edukt 2

HCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 866547266-(cis-2-amino-3,3-difluorocyclohexylamino)-4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one

Produkt 1

HCID 672390206-(cis-2-Amino-3,3-difluorocyclohexylamino)-2-(2,4-dimethoxybenzyl)-7-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,4-c]pyridin-3(2H)-one

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A microwave vial was charged with 6-(cis-2-amino-3,3-difluorocyclohexylamino)-4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one (13.7 mg, 0.028 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (8.82 mg, 0.042 mmol) and bis(triphenylphosphine)palladium chloride (3.97 mg, 5.65 μmol) and placed under an inert environment. DME (283 μL) was added to the mixture and the resulting yellow slurry was degassed for 5 min. Sodium carbonate was added (56.5 μL, 0.113 mmol) and the slurry degassed for an additional 3 min. The vessel was capped and the mixture was heated at 80° C. for 4 h, cooled to ambient temperature, diluted with EtOAc (5 mL), and washed with water (3 mL) and brine (3 mL). The organic layer was collected, dried over sodium sulfate, and concentrated to give the title compound as a dark brown residue which was used in the next step without further purification (21 mg). [M+H] calc'd for C26H29F3N6O3, 531. found, 531.

Aufarbeitung

  1. customthe resulting yellow slurry was degassed for 5 min
  2. additionSodium carbonate was added (56.5 μL, 0.113 mmol)
  3. customthe slurry degassed for an additional 3 min
  4. customThe vessel was capped
  5. temperaturecooled to ambient temperature
  6. additiondiluted with EtOAc (5 mL)
  7. washwashed with water (3 mL) and brine (3 mL)
  8. customThe organic layer was collected
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-e1d110a512bc4e8db6937f15c7d9b6d2
Quelldatensatz
uspto-grants-2013_05
Patentnummer
US08440689B2

Notizen zur Reaktion

Wird geladen…