Dimethyl Sulfoxide → HCID 72549726, compound

HRID 705503Notes

Reaction equation

HRID 705503 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].[N:24]1[C:33]2[C:28](=CC=C[C:32]=2O)[CH:27]=[CH:26][CH:25]=1.[C:35](=[O:38])([O-])[O-].[K+].[K+].CS(C)=O>CCOC(C)=O.[Cu]I>[OH:16][CH:13]1[CH2:12][CH2:11][N:10]([C:28]2[CH:27]=[CH:26][C:25]([N:20]3[CH:21]=[CH:22][C:17]([O:16][CH:13]4[CH2:14][CH2:15][N:10]([C:7]5[N:8]=[CH:9][C:4]([CH2:1][CH2:2][CH3:3])=[CH:5][N:6]=5)[CH2:11][CH2:12]4)=[CH:18][C:19]3=[O:23])=[N:24][C:33]=2[CH3:32])[C:35]1=[O:38]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 19238-HydroxyquinolineHCID 11430Potassium CarbonateHCID 670725174-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one

Product 1

HCID 72549726HCID 72549726, compoundYield 98%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

A 25 mL round bottom flask was charged with 4-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)pyridin-2(1H)-one (116 mg, 0.369 mmol) (prepared according to the procedure described in patent application WO-2009/012275), Intermediate 4 (120 mg, 0.443 mmol), quinolin-8-ol (21.4 mg, 0.148 mmol), potassium carbonate (66.3 mg, 0.480 mmol), copper(I) iodide (28.1 mg, 0.148 mmol) and DMSO (3 mL). The mixture was heated under Ar to 140° C. for 5 hours and then allowed to cool to room temperature overnight. The resulting mixture was diluted with EtOAc (100 mL) and washed with H2O (100 mL). The organic layer was concentrated in vacuo to a brown oil, which was purified by flash chromatography (SiO2, 0 to 70% Acetone in CH2Cl2) to give example 5 (73.2 mg, 39% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.22 (s, 2H), 7.82 (dd, J=8.1, 5.5 Hz, 2H), 7.64 (d, J=8.4 Hz, 1H), 6.09 (dd, J=7.8, 2.6 Hz, 1H), 6.02 (d, J=2.5 Hz, 1H), 5.75 (d, J=5.7 Hz, 1H), 4.69-4.84 (m, 1H), 4.28-4.38 (m, 1H), 4.11-4.26 (m, 2H), 3.57-3.74 (m, 2H), 3.40-3.54 (m, 2H), 2.40-2.47 (m, 1H), 2.31-2.40 (m, 5H), 1.91-2.07 (m, 3H), 1.45-1.65 (m, 4H), 0.87 (t, J=7.3 Hz, 3H). MS (ESI) 505 (M+H).

Workup

  1. customprepared
  2. temperatureto cool to room temperature overnight
  3. washwashed with H2O (100 mL)
  4. concentrationThe organic layer was concentrated in vacuo to a brown oil, which
  5. customwas purified by flash chromatography (SiO2, 0 to 70% Acetone in CH2Cl2)

Sources & evidence

ORD record
ord-ca8ea7e7563e401181ffb1cbd8f70758
Source dataset
uspto-grants-2015_11
Patent number
US09174965B2

Reaction notes

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