Potassium Iodide → 5-{3-[1-(4-Amino-6-iodo-5-oxopyrido[2,3-d]pyrimidin-8(5H)-yl)ethyl]-5-chloro-2-methoxy-6-methylphenyl}-N,N-dimethylpyridine-2-carboxamide

HRID 1499969Notes

Reaction equation

[NH2:1][C:2]1[C:3]2[C:11](=[O:12])[C:10]([I:13])=[CH:9][NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[K+].[Cl:22][C:23]1[C:24]([CH3:45])=[C:25]([C:34]2[CH:35]=[CH:36][C:37]([C:40]([N:42]([CH3:44])[CH3:43])=[O:41])=[N:38][CH:39]=2)[C:26]([O:32][CH3:33])=[C:27]([CH:29](Cl)[CH3:30])[CH:28]=1>CN(C=O)C.CO>[NH2:1][C:2]1[C:3]2[C:11](=[O:12])[C:10]([I:13])=[CH:9][N:8]([CH:29]([C:27]3[C:26]([O:32][CH3:33])=[C:25]([C:34]4[CH:35]=[CH:36][C:37]([C:40]([N:42]([CH3:43])[CH3:44])=[O:41])=[N:38][CH:39]=4)[C:24]([CH3:45])=[C:23]([Cl:22])[CH:28]=3)[CH3:30])[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

Conditions

Temperature: 140 °C

Procedure

To a mixture of 4-amino-6-iodopyrido[2,3-d]pyrimidin-5(8H)-one (255 mg, 0.885 mmol), cesium carbonate (0.43 g, 1.3 mmol) and potassium iodide (14.7 mg, 0.0885 mmol) in DMF (9.4 mL) was added 5-{3-chloro-5-(1-chloroethyl)-6-methoxy-2-methylphenyl}-N,N-dimethylpyridine-2-carboxamide (325 mg, 0.885 mmol) (from example 25 step 1) and the mixture was stirred at 140° C. for 1 h. The mixture was diluted with methanol and purified 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 compound (221 mg, 40%). LCMS calculated for C25H25ClIN6O3 (M+H)+: m/z=619.1; Found: 619.0.

Workup

custompurified on RP-HPLC (XBridge C18 column
washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min)

Sources & evidence

ORD record: ord-bbe7e9cf88ac48a2a2799195ddd9dd6d
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09199982B2

Reaction notes

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