Potassium Iodide → US10092570, Example 25

HRID 1499711Notes

Reaction equation

HRID 1499711 reaction equation
[NH2:1][C:2]1[C:3]2[C:11](=[O:12])[CH:10]=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[K+].[Cl:21][C:22]1[C:23]([CH3:44])=[C:24]([C:33]2[CH:34]=[CH:35][C:36]([C:39]([N:41]([CH3:43])[CH3:42])=[O:40])=[N:37][CH:38]=2)[C:25]([O:31][CH3:32])=[C:26]([CH:28](Cl)[CH3:29])[CH:27]=1>CN(C)C=O>[NH2:1][C:2]1[C:3]2[C:11](=[O:12])[CH:10]=[CH:9][N:8]([CH:28]([C:26]3[C:25]([O:31][CH3:32])=[C:24]([C:33]4[CH:34]=[CH:35][C:36]([C:39]([N:41]([CH3:42])[CH3:43])=[O:40])=[N:37][CH:38]=4)[C:23]([CH3:44])=[C:22]([Cl:21])[CH:27]=3)[CH3:29])[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 57067884-aminopyrido[2,3-d]pyrimidin-5(8H)-oneHCID 866776325-[3-chloro-5-(1-chloroethyl)-6-methoxy-2-methylphenyl]N,N-dimethylpyridine-2-carboxamide

Product 1

HCID 71510360US10092570, Example 25

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

To a mixture of 4-aminopyrido[2,3-d]pyrimidin-5(8H)-one (from VWR, 4.8 mg, 0.030 mmol), cesium carbonate (14 mg, 0.044 mmol) and potassium iodide (0.50 mg, 0.0030 mmol) in N,N-dimethylformamide (0.1 mL) was added 5-[3-chloro-5-(1-chloroethyl)-6-methoxy-2-methylphenyl]-N,N-dimethylpyridine-2-carboxamide (11 mg, 0.030 mmol). The mixture was stirred at 140° C. for 1 hour. The reaction mixture was applied on RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give the desired product. LCMS calculated for C25H26ClN6O3 (M+H)+: m/z=493.2; Found: 493.1. The racemic products were applied on a Phenomenex Lux-Cellulose 1 column (21.1×250 mm, 5 micron particle size), eluting with 30% ethanol in hexanes at a flow rate of 18 mL/min, 4.2 mg/injection, to provide two isolated enantiomers. This first isolated peak had a retention time of 15.39 min and the second peak had a retention time of 22.98. For the second peak: 1H NMR (CDCl3, 400 MHz) δ 9.86 (d, J=5.6 Hz, 1H), 8.36 (m, 1H), 8.30 (s, 1H), 7.65-7.58 (m, 2H), 7.37 (m, 2H), 6.84 (q, J=7.2 Hz, 1H), 6.22 (d, J=8.0 Hz), 5.95 (d, J=5.2 Hz, 1H), 3.08 (s, 3H), 3.05 (s, 3H), 2.93 (m, 3H), 2.09 (s, 3H), 1.68 (d, J=7.2 Hz, 3H) ppm.

Workup

  1. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min)

Sources & evidence

ORD record
ord-b729745862d849aaa1a38c54b5764e56
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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