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

HRID 1454470Notes

Reaction equation

HRID 1454470 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[CH2:18][CH2:17][CH2:16][CH2:15]3)[CH2:10][CH2:9]2)[N:5]=[C:4]2[N:19]([C:24]3[C:29]([F:30])=[CH:28][CH:27]=[CH:26][C:25]=3[F:31])[C:20](=[O:23])[NH:21][CH2:22][C:3]=12.O.C(=O)([O-])[O-].[K+].[K+].[F:39][C:40]1[CH:45]=[CH:44][C:43]([NH:46][C:47](=[O:64])[C:48]2[CH:53]=[CH:52][C:51]([CH3:54])=[C:50](B3OC(C)(C)C(C)(C)O3)[CH:49]=2)=[CH:42][CH:41]=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>[F:30][C:29]1[CH:28]=[CH:27][CH:26]=[C:25]([F:31])[C:24]=1[N:19]1[C:4]2[N:5]=[C:6]([N:8]3[CH2:9][CH2:10][CH:11]([N:14]4[CH2:15][CH2:16][CH2:17][CH2:18]4)[CH2:12][CH2:13]3)[N:7]=[C:2]([C:50]3[CH:49]=[C:48]([CH:53]=[CH:52][C:51]=3[CH3:54])[C:47]([NH:46][C:43]3[CH:44]=[CH:45][C:40]([F:39])=[CH:41][CH:42]=3)=[O:64])[C:3]=2[CH2:22][NH:21][C:20]1=[O:23]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 119516925-chloro-1-(2,6-difluorophenyl)-7-[4-(1-pyrrolidinyl)-1-piperidinyl]-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-oneHCID 57416195N-(4-fluorophenyl)-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide

Product 1

HCID 575305123-{8-(2,6-difluorophenyl)-7-oxo-2-[4-(1-pyrrolidinyl)-1-piperidinyl]-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-yl}-N-(4-fluorophenyl)-4-methylbenzamideYield 54.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 5-chloro-1-(2,6-difluorophenyl)-7-[4-(1-pyrrolidinyl)-1-piperidinyl]-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 about 150° C. for about 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 (14 mg, 54%).

Workup

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

Sources & evidence

ORD record
ord-9e3d42779678464983512f8a46187708
Source dataset
uspto-grants-2009_01
Patent number
US07479558B2

Reaction notes

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