Water → 4-(4,4-Difluoropiperidin-1-yl)-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5,5-dimethyl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one

HRID 536528

Reaktionsgleichung

Reaktionsgleichung von HRID 536528
[F:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:12]=[C:13](I)[C:14]4[C:19]([CH3:21])([CH3:20])[C:18](=[O:22])[NH:17][C:15]=4[N:16]=3)=[N:9][N:8]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[F:31])[C:5]2=[N:6][CH:7]=1.C(N(CC)C(C)C)(C)C.Cl.[F:42][C:43]1([F:49])[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1.O>CN1CCCC1=O>[F:42][C:43]1([F:49])[CH2:48][CH2:47][N:46]([C:13]2[C:14]3[C:19]([CH3:21])([CH3:20])[C:18](=[O:22])[NH:17][C:15]=3[N:16]=[C:11]([C:10]3[C:4]4[C:5](=[N:6][CH:7]=[C:2]([F:1])[CH:3]=4)[N:8]([CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=4[F:31])[N:9]=3)[N:12]=2)[CH2:45][CH2:44]1

Komponenten

6

Edukt 4

HCID 962WaterHCID 81531Diisopropylethylamine2×HCID 27583514,4-Difluoropiperidine hydrochloride2×HCID 867053662-[5-Fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-4-iodo-5,5-dimethyl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one

Produkt 1

HCID 712902924-(4,4-Difluoropiperidin-1-yl)-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-5,5-dimethyl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-oneAusbeute 66,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

100 mg (0.18 mmol) of 2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-4-iodo-5,5-dimethyl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one (example 16A) was dissolved in 1-methyl-2-pyrrolidone (3.1 ml) in a reaction vessel suitable for a microwave, and 0.19 ml (1.07 mmol) of N,N-diisopropyl ethylamine and 140 mg (0.89 mmol) of 4,4-difluoropiperidine hydrochloride were added. Then the reaction vessel was sealed with a septum and was heated in the microwave for 5 h at 150° C. Then the same amounts of N,N-diisopropyl ethylamine and 4,4-difluoropiperidine hydrochloride were added again to the reaction solution and the reaction mixture was stirred for 6 h at 150° C. in the microwave. Water was added to the reaction mixture, the precipitated solid was stirred for 30 min at room temperature and then filtered off. The precipitated solid was stirred with 1 ml acetonitrile, the solid was filtered off and was washed with 0.5 ml acetonitrile. 63 mg of the target compound (64% of theor.) was obtained.

Aufarbeitung

  1. additionwere added
  2. customThen the reaction vessel was sealed with a septum
  3. stirringthe precipitated solid was stirred for 30 min at room temperature
  4. filtrationfiltered off
  5. stirringThe precipitated solid was stirred with 1 ml acetonitrile
  6. filtrationthe solid was filtered off
  7. washwas washed with 0.5 ml acetonitrile

Quellen und Nachweise

ORD-Eintrag
ord-63efb829cd884fab97ccb883ec81241a
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08859569B2

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