Potassium Carbonate → 4-Quinolin-4-yl-piperidine-1-carboxylic acid (4-isopropyl-phenyl)-amide

HRID 657193Notes

Reaction equation

[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.[N+](C1C=CC([O:26][C:27](=O)[NH:28][C:29]2[CH:34]=[CH:33][C:32]([CH:35]([CH3:37])[CH3:36])=[CH:31][CH:30]=2)=CC=1)([O-])=O.CCN(C(C)C)C(C)C.C([O-])([O-])=O.[K+].[K+]>CS(C)=O>[CH:35]([C:32]1[CH:33]=[CH:34][C:29]([NH:28][C:27]([N:1]2[CH2:2][CH2:3][CH:4]([C:7]3[C:16]4[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=4)[N:10]=[CH:9][CH:8]=3)[CH2:5][CH2:6]2)=[O:26])=[CH:30][CH:31]=1)([CH3:37])[CH3:36]

Participants

Conditions

Temperature: 100 °C

Procedure

A solution of 4-piperidin-4-yl-quinoline (21.1 mg, 99.5 μmol), as prepared in the previous step, (4-isopropyl-phenyl)-carbamic acid 4-nitro-phenyl ester (33.2 mg, 111 μmol), as prepared in Example 4a, and DIEA (18 μL, 109 μmol) in DMSO (100 μL) was stirred at 100° C. for 14 h. The reaction was then allowed to cool to rt, shaken with 2 M K2CO3 (aq) (2 mL), and extracted with DCM (2×2 mL). The organic layers were combined, dried (Na2SO4), and concentrated under reduced pressure. Flash chromatography of the residue (3:4 hex/acetone) provided the title compound (12 mg, 32%). 1H-NMR (300 MHz, CDCl3) δ 8.88 (d, 1H), 8.14 (m, 2H), 7.74 (m, 1H), 7.61 (m, 1H), 7.30 (m, 2H), 7.28 (d, 1H), 7.17 (m, 2H), 6.38 (br s, 1H), 4.36-4.26 (m, 2H), 3.58 (m, 1H), 3.16 (td, 2H), 2.87 (heptet, 1H), 2.13-2.03 (m, 2H), 1.95-1.79 (m, 2H), 1.23 (d, 6H). LC/MS (ESI): calcd mass 373.2, found 374.2 (MH)+.

Workup

temperatureto cool to rt
extractionextracted with DCM (2×2 mL)
dry with materialdried (Na2SO4)
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-fe667763e72540c49ee6a33cb96e44ee
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08071768B2

Reaction notes

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