Water → 3-[2-(1,4'-bipiperidin-1'-yl)-8-(2,6-difluorophenyl)-7-oxo-5,6,7,8-tetrahydropyrimido [4,5-d]pyrimidin-4-yl]-N-(4-fluorophenyl)-4-methylbenzamide

HRID 2243725Notes

Reaction equation

HRID 2243725 reaction equation
[N:1]1([CH:7]2[CH2:12][CH2:11][N:10]([C:13]3[N:18]=[C:17]4[N:19]([C:24]5[C:29]([F:30])=[CH:28][CH:27]=[CH:26][C:25]=5[F:31])[C:20](=[O:23])[NH:21][CH2:22][C:16]4=[C:15](Cl)[N:14]=3)[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.O.C(=O)([O-])[O-].[K+].[K+].[F:40][C:41]1[CH:46]=[CH:45][C:44]([NH:47][C:48](=[O:65])[C:49]2[CH:54]=[CH:53][C:52]([CH3:55])=[C:51](B3OC(C)(C)C(C)(C)O3)[CH:50]=2)=[CH:43][CH:42]=1>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:1]1([CH:7]2[CH2:12][CH2:11][N:10]([C:13]3[N:14]=[C:15]([C:51]4[CH:50]=[C:49]([CH:54]=[CH:53][C:52]=4[CH3:55])[C:48]([NH:47][C:44]4[CH:45]=[CH:46][C:41]([F:40])=[CH:42][CH:43]=4)=[O:65])[C:16]4[CH2:22][NH:21][C:20](=[O:23])[N:19]([C:24]5[C:29]([F:30])=[CH:28][CH:27]=[CH:26][C:25]=5[F:31])[C:17]=4[N:18]=3)[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 57416195N-(4-fluorophenyl)-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 575305197-(1,4'-bipiperidin-1'-yl)-5-chloro-1-(2,6-difluorophenyl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one

Product 1

HCID 575305083-[2-(1,4'-bipiperidin-1'-yl)-8-(2,6-difluorophenyl)-7-oxo-5,6,7,8-tetrahydropyrimido [4,5-d]pyrimidin-4-yl]-N-(4-fluorophenyl)-4-methylbenzamideYield 51%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of compound 7-(1,4′-bipiperidin-1′-yl)-5-chloro-1-(2,6-difluorophenyl)-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one (18 mg, 0.04 mmol) in dioxane (1.5 mL)/water (0.5 mL) were added potassium carbonate (34 mg, 0.25 mmol), tetrakis(triphenylphosphine)palladium(0) (2.3 mg, 0.002 mmol) and N-(4-fluorophenyl)-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (22 mg, 0.062 mmol). The reaction mixture was bubbled with N2 for 5 mins, then microwaved at 150° C. for 30 mins. The reaction mixture was concentrated. CombiFlash chromatography (mobile phase DCM/DCM[90]+MeOH [7]+NH4OH[3]) provided the title compound as a white solid (13 mg, 51%). LC-MS m/z 656 (M+H)+; 1H-NMR (MeOD) δ 1.37 (m, 2H), 1.48 (m, 2H), 1.60 (m, 4H), 1.80 (m, 2H), 2.33 (s, 3H), 2.56 (m, 5H), 2.72 (t, 2H), 4.17 (m, 2H), 4.46 (m, 2H), 7.12 (m, 4H), 7.52 (m, 2H), 7.72 (m, 2H), 7.82 (s, 1H), 7.98 (d, 1H).

Workup

  1. customThe reaction mixture was bubbled with N2 for 5 mins
  2. custommicrowaved at 150° C. for 30 mins
  3. concentrationThe reaction mixture was concentrated

Sources & evidence

ORD record
ord-5e7f1be1e53a4b70b3260b590ade1025
Source dataset
uspto-grants-2010_03
Patent number
US07674789B2

Reaction notes

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