Diisopropylethylamine → 4-[3-Fluoro-5-(1-methyl-imidazo[1,5-a]quinolin-7-ylsulfanyl)-phenyl]-tetrahydro-pyran-4-carbonitrile

HRID 2075682Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]1[C:12]([CH3:15])=[N:13][CH:14]=[C:7]1[CH:6]=[CH:5]2.[F:16][C:17]1[CH:18]=[C:19]([C:24]2([C:30]#[N:31])[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[CH:20]=[C:21]([SH:23])[CH:22]=1.CCN(C(C)C)C(C)C.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>O1CCOCC1.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]>[F:16][C:17]1[CH:18]=[C:19]([C:24]2([C:30]#[N:31])[CH2:25][CH2:26][O:27][CH2:28][CH2:29]2)[CH:20]=[C:21]([S:23][C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]2[C:12]([CH3:15])=[N:13][CH:14]=[C:7]2[CH:6]=[CH:5]3)[CH:22]=1

Participants

Conditions

Temperature: 80 °C

Procedure

4d (80 mg, 0.3 mmol) and 4-(3-Fluoro-5-mercapto-phenyl)-tetrahydro-pyran-4-carbonitrile (4e, 88 mg, 0.37 mmol) were dissolved in 1,4-dioxane (3 mL) and degassed for 10 minutes with N2. iPr2NEt (0.10 mL, 0.6 mmol), Pd2dba3 (14 mg, 0.02 mmol), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (17 mg, 0.03 mmol) were added, and the reaction was degassed for another 10 minutes with N2. The reaction was then sealed and heated to 80° C. overnight. After cooling to room temperature, the reaction was concentrated and purified by silica gel chromatography (0-20% MeOH in EtOAc) to give the desired product, 4f.

Workup

customdegassed for 10 minutes with N2
customthe reaction was degassed for another 10 minutes with N2
customThe reaction was then sealed
temperatureAfter cooling to room temperature
concentrationthe reaction was concentrated
custompurified by silica gel chromatography (0-20% MeOH in EtOAc)

Sources & evidence

ORD record: ord-ba83cd971ad74d1991c51dbf3852ab30
Source dataset: uspto-grants-2011_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07919621B2

Reaction notes

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