8-Hydroxyquinoline → 1-(2-methyl-4-(methylsulfonyl)phenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

HRID 1895728Notes

Reaction equation

HRID 1895728 reaction equation
[CH2:1]([C:4]1[CH:5]=[N:6][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([O:16][C:17]3[CH:22]=[CH:21][NH:20][C:19](=[O:23])[CH:18]=3)[CH2:12][CH2:11]2)=[N:8][CH:9]=1)[CH2:2][CH3:3].CS(OC1CCN(C(OC(C)C)=O)CC1)(=O)=O.F[C:42]1[CH:47]=[CH:46][C:45]([S:48]([CH3:51])(=[O:50])=[O:49])=[CH:44][C:43]=1[CH3:52].BrC1C=CC(C#N)=CC=1.C(=O)([O-])[O-].[K+].[K+].N1C2C(=CC=CC=2O)C=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>[Cu]I>[CH3:52][C:43]1[CH:44]=[C:45]([S:48]([CH3:51])(=[O:50])=[O:49])[CH:46]=[CH:47][C:42]=1[N:20]1[CH:21]=[CH:22][C:17]([O:16][CH:13]2[CH2:14][CH2:15][N:10]([C:7]3[N:8]=[CH:9][C:4]([CH2:1][CH2:2][CH3:3])=[CH:5][N:6]=3)[CH2:11][CH2:12]2)=[CH:18][C:19]1=[O:23]

Participants

9

Reactant 7

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 12162Benzonitrile, 4-bromo-HCID 215752401-Fluoro-4-(methanesulfonyl)-2-methylbenzeneHCID 59158905Isopropyl 4-(methylsulfonyloxy)piperidine-1-carboxylateHCID 670725174-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Product 1

HCID 574684121-(2-methyl-4-(methylsulfonyl)phenyl)-4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Procedure

Example 178 was prepared according to the procedures described in Example 162 substituting 4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one for isopropyl 4-(methylsulfonyloxy)piperidine-1-carboxylate and 1-fluoro-2-methyl-4-(methylsulfonyl)benzene for 4-bromobenzonitrile in Step C except that the reaction was heated at 160° C. for 20 min. with copper(I) iodide, potassium carbonate and quinolin-8-ol in a Microwave as described in Step A of Example 1 instead of reflux at 120° C. in the presence of cesium carbonate for 10 h. 1H NMR (500 MHz, CDCl3) δ ppm 8.21 (br. s., 2 H), 7.92 (s, 1 H), 7.88 (d, J=7.70 Hz, 1 H), 7.40 (d, J=7.70 Hz, 1 H), 7.06 (d, J=6.05 Hz, 1 H), 5.93-6.11 (m, 2 H), 4.58 (br. s., 1 H), 4.21 (br. s., 2 H), 3.56-3.80 (m, 2 H), 3.08 (s, 3 H), 2.41 (t, J=7.42 Hz, 2 H), 2.28 (s, 3 H), 2.09 (d, J=9.90 Hz, 2 H), 1.87 (br. s., 2 H), 1.48-1.65 (m, 2 H), 0.93 (t, J=7.42 Hz, 3 H). MS (ESI) 483 (M+H).

Workup

  1. customExample 178 was prepared

Sources & evidence

ORD record
ord-9724a74bbad44c0a88d6a9776d5d1b5f
Source dataset
uspto-grants-2013_08
Patent number
US08513424B2

Reaction notes

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