Cesium carbonate → 1-(7-Acetyl-5-chloroquinolin-8-yl)pyrrolidine-3-carbonitrile

HRID 1192600Notes

Reaction equation

FC(F)(F)S(O[C:7]1[C:8]([C:18](=[O:20])[CH3:19])=[CH:9][C:10]([Cl:17])=[C:11]2[C:16]=1[N:15]=[CH:14][CH:13]=[CH:12]2)(=O)=O.Cl.[NH:24]1[CH2:28][CH2:27][CH:26]([C:29]#[N:30])[CH2:25]1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:18]([C:8]1[C:7]([N:24]2[CH2:28][CH2:27][CH:26]([C:29]#[N:30])[CH2:25]2)=[C:16]2[C:11]([CH:12]=[CH:13][CH:14]=[N:15]2)=[C:10]([Cl:17])[CH:9]=1)(=[O:20])[CH3:19]

Participants

Conditions

Temperature: 65 °C

Procedure

A stirred mixture of 7-acetyl-5-chloroquinolin-8-yl trifluoromethanesulfonate (0.12 g, 0.34 mmol, from Example 47, Step 2), pyrrolidine-3-carbonitrile hydrochloride (0.054 g, 0.41 mmol), palladium acetate (1.5 mg, 0.0068 mmol), (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (6.3 mg, 0.010 mmol), and cesium carbonate (0.31 g, 0.95 mmol) in tetrahydrofuran (3 mL) was heated at 65° C. overnight. The mixture was cooled, diluted with dichloromethane and filtered. The filtrate was washed with brine, dried over MgSO4 and evaporated to dryness. The resulting residue was purified on silica gel (eluting with 0 to 5% MeOH in dichloromethane) to give the desired product (16 mg, 16%). LCMS calculated for C16H15ClN3O (M+H)+: m/z=300.1; Found: 300.0.

Workup

temperatureThe mixture was cooled
filtrationfiltered
washThe filtrate was washed with brine
dry with materialdried over MgSO4
customevaporated to dryness
customThe resulting residue was purified on silica gel (eluting with 0 to 5% MeOH in dichloromethane)

Sources & evidence

ORD record: ord-aaaf1407e22e4f7fb92131cc7fd2c91b
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08680108B2

Reaction notes

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