Binap, (A+-)- → 1-[(4-{[tert-Butyl(dimethyl)silyl]oxy}-3-fluorocyclohexyl)amino]-8-fluoro-5H-pyrido[4,3-b]indole-4-carbonitrile

HRID 1971019Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1971019
Cl[C:2]1[C:14]2[C:13]3[CH:12]=[C:11]([F:15])[CH:10]=[CH:9][C:8]=3[NH:7][C:6]=2[C:5]([C:16]#[N:17])=[CH:4][N:3]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])(C)C.[K+].[Si:70]([O:77][CH:78]1[CH2:83][CH2:82][CH:81]([NH2:84])[CH2:80][CH:79]1[F:85])([C:73]([CH3:76])([CH3:75])[CH3:74])([CH3:72])[CH3:71]>CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].COCCOC>[Si:70]([O:77][CH:78]1[CH2:83][CH2:82][CH:81]([NH:84][C:2]2[C:14]3[C:13]4[CH:12]=[C:11]([F:15])[CH:10]=[CH:9][C:8]=4[NH:7][C:6]=3[C:5]([C:16]#[N:17])=[CH:4][N:3]=2)[CH2:80][CH:79]1[F:85])([C:73]([CH3:76])([CH3:75])[CH3:74])([CH3:72])[CH3:71]

Komponenten

8

Edukt 4

HCID 634876Binap, (A+-)-HCID 23665647Potassium tert-butoxideHCID 591984921-chloro-8-fluoro-5H-pyrido[4,3-b]indole-4-carbonitrileHCID 595431224-{[tert-Butyl(dimethyl)silyl]oxy}-3-fluorocyclohexanamine

Produkt 1

HCID 595431201-[(4-{[tert-Butyl(dimethyl)silyl]oxy}-3-fluorocyclohexyl)amino]-8-fluoro-5H-pyrido[4,3-b]indole-4-carbonitrile

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

A flask containing 1-chloro-8-fluoro-5H-pyrido[4,3-b]indole-4-carbonitrile (Example 38 Step 4, 250 mg, 1.02 mmol), BINAP (95 mg, 0.15 mmol), Pd2(dba)3 (47 mg, 0.051 mmol), and KOtBu (365 mg, 3.26 mmol) was evacuated and refilled with nitrogen (×3). Degassed DME (5 mL) and 4-{[tert-butyl(dimethyl)silyl]oxy}-3-fluorocyclohexanamine (327 mg, 1.32 mmol) were added to the mixture. The reaction mixture was heated to 85° C. overnight, cooled to room temperature, diluted with EtOAc, and washed with water and brine. The organic layer was dried (sodium sulfate), concentrated, and purified by flash chromatography to afford the title compound. LRMS (APCI) calc'd for (C24H30F2N4OSi) [M+H]+, 457.2. found 457.1.

Aufarbeitung

  1. customwas evacuated
  2. additionrefilled with nitrogen (×3)
  3. temperaturecooled to room temperature
  4. washwashed with water and brine
  5. dry with materialThe organic layer was dried (sodium sulfate)
  6. concentrationconcentrated
  7. custompurified by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-0dfb8b7953dc4fbc93bc65416f2c4975
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08431569B2

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