Potassium Carbonate → N-cyclopropyl-3-(8-(2,6-difluorophenyl)-2-{[2-hydroxy-1-(hydroxymethyl)ethyl]amino}-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl)-5-fluoro-4-methylbenzamide

HRID 1454455Notes

Reaction equation

Cl[C:2]1[C:3]2[CH:17]=[CH:16][C:15](=[O:18])[N:14]([C:19]3[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=3[F:26])[C:4]=2[N:5]=[C:6]([NH:8][CH:9]([CH2:12][OH:13])[CH2:10][OH:11])[N:7]=1.[CH:27]1([NH:30][C:31](=[O:49])[C:32]2[CH:37]=[C:36](B3OC(C)(C)C(C)(C)O3)[C:35]([CH3:47])=[C:34]([F:48])[CH:33]=2)[CH2:29][CH2:28]1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O>[CH:27]1([NH:30][C:31](=[O:49])[C:32]2[CH:33]=[C:34]([F:48])[C:35]([CH3:47])=[C:36]([C:2]3[C:3]4[CH:17]=[CH:16][C:15](=[O:18])[N:14]([C:19]5[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=5[F:26])[C:4]=4[N:5]=[C:6]([NH:8][CH:9]([CH2:12][OH:13])[CH2:10][OH:11])[N:7]=3)[CH:37]=2)[CH2:28][CH2:29]1

Participants

Conditions

Temperature: 100 °C

Procedure

4-Chloro-8-(2,6-difluorophenyl)-2-{[2-hydroxy-1-(hydroxymethyl)ethyl]-amino}pyrido[2,3-d]pyrimidin-7(8H)-one (0.056 g, 0.17 mmol), N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (0.065 g, 0.17 mmol), K2CO3 (0.07 g, 0.51 mmol) and tetrakis triphenyl phosphine palladium (10 mg, 0.05 eq) are dissolved in dioxane/water (3:1, 10 mL) and heated to about 100° C. for about 3 h. The mixture is concentrated and purified via reverse phase HPLC to afford the title compound (9 mg, yellow powder, mp 214.2-217.5): LC-MS m/z 540 (M+H)+, 1.69 min (ret time). HPLC indicates 96% pure.

Workup

concentrationThe mixture is concentrated
custompurified via reverse phase HPLC

Sources & evidence

ORD record: ord-0d13a288d214442b934e824694a7c748
Source dataset: uspto-grants-2009_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07479558B2

Reaction notes

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