N-Methylcyclohexylamine → N-cyclohexyl-5-fluoro-N-methyl-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-amine

HRID 1696207Notes

Reaction equation

Cl[C:2]1[C:7]([F:8])=[CH:6][N:5]=[C:4]2[N:9]([Si:12]([CH:19]([CH3:21])[CH3:20])([CH:16]([CH3:18])[CH3:17])[CH:13]([CH3:15])[CH3:14])[CH:10]=[CH:11][C:3]=12.[CH3:22][NH:23][CH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1.CC(C)([O-])C.[Na+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(CCC)=CC(CCC)=CC=2CCC)CCCCC1>CC([O-])=O.CC([O-])=O.[Pd+2].O1CCOCC1>[CH:24]1([N:23]([CH3:22])[C:2]2[C:3]3[CH:11]=[CH:10][N:9]([Si:12]([CH:19]([CH3:21])[CH3:20])([CH:16]([CH3:18])[CH3:17])[CH:13]([CH3:15])[CH3:14])[C:4]=3[N:5]=[CH:6][C:7]=2[F:8])[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 4-chloro-5-fluoro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (250 mg), N-methylcyclohexanamine (306 μl), Pd(OAc)2(17 mg), sodium tert-butoxide (176 mg), 2-dicyclohexylphosphino-2′,4′,6′-tri-1-propyl-1,1′-biphenyl (73 mg) and 1,4-dioxane (2.5 mL) was evacuated and backfield with N2 three times, then degassed with N2 for 10 minutes. The mixture was heated at 100° C. for 2.5 hours. After cooling to ambient temperature, the reaction mixture was concentrated. Purification of the crude product by column chromatography (silica gel, n-hexane:EtOAc=1:50) afforded N-cyclohexyl-5-fluoro-N-methyl-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridin-4-amine (53 mg) as a colorless solid.

Workup

customwas evacuated
customdegassed with N2 for 10 minutes
temperatureAfter cooling to ambient temperature
concentrationthe reaction mixture was concentrated
customPurification of the crude product by column chromatography (silica gel, n-hexane:EtOAc=1:50)

Sources & evidence

ORD record: ord-68073a08ca904e9a974dca3ee63f2326
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08163767B2

Reaction notes

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