Cesium carbonate → N-[1-(7-acetyl-5-chloroquinolin-8-yl)piperidin-4-yl]methanesulfonamide

HRID 1192648Notes

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[CH2:29][CH2:28][CH:27]([NH:30][S:31]([CH3:34])(=[O:33])=[O:32])[CH2:26][CH2:25]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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:18]([C:8]1[C:7]([N:24]2[CH2:25][CH2:26][CH:27]([NH:30][S:31]([CH3:34])(=[O:32])=[O:33])[CH2:28][CH2:29]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 (0.16 g, 0.22 mmol, from Example 47, Step 2), N-piperidin-4-ylmethanesulfonamide hydrochloride (0.040 g, 0.19 mmol), palladium acetate (0.84 mg, 0.0037 mmol), (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (3.5 mg, 0.0056 mmol), and cesium carbonate (0.23 g, 0.71 mmol) in tetrahydrofuran (4 mL) was heated at 65° C. overnight. The mixtures was cooled, diluted with dichloromethane and filtered. The filtrate was washed with brine, dried over MgSO4, evaporated and purified on silica gel (eluting with 0 to 5% methanol in dicholomethane) to give the desired product (27 mg, 38%). LCMS calculated for C17H21ClN3O3S (M+H)+: m/z=382.1; Found: 382.0.

Workup

temperatureThe mixtures was cooled
filtrationfiltered
washThe filtrate was washed with brine
dry with materialdried over MgSO4
customevaporated
custompurified on silica gel (eluting with 0 to 5% methanol in dicholomethane)

Sources & evidence

ORD record: ord-dbd553e681434934a9795c899e611889
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08680108B2

Reaction notes

Loading…