Cesium carbonate → 1-(2,6-Dichloro-3,5-dimethoxy-phenyl)-3-[6-(4-dimethylaminomethyl-2-nitro phenylamino)-pyrimidin-4-yl]-3-methyl-1-(2-trimethylsilanyl-ethoxymethyl)-urea

HRID 58147Notes

Reaction equation

HRID 58147 reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([N:8]([CH3:32])[C:9]([N:11]([C:20]2[C:25]([Cl:26])=[C:24]([O:27][CH3:28])[CH:23]=[C:22]([O:29][CH3:30])[C:21]=2[Cl:31])[CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])=[O:10])[CH:3]=1.[CH3:33][N:34]([CH2:36][C:37]1[CH:42]=[CH:41][C:40]([NH2:43])=[C:39]([N+:44]([O-:46])=[O:45])[CH:38]=1)[CH3:35].C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CO>[Cl:26][C:25]1[C:24]([O:27][CH3:28])=[CH:23][C:22]([O:29][CH3:30])=[C:21]([Cl:31])[C:20]=1[N:11]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:18])([CH3:19])[CH3:17])[C:9]([N:8]([C:4]1[CH:3]=[C:2]([NH:43][C:40]2[CH:41]=[CH:42][C:37]([CH2:36][N:34]([CH3:35])[CH3:33])=[CH:38][C:39]=2[N+:44]([O-:46])=[O:45])[N:7]=[CH:6][N:5]=1)[CH3:32])=[O:10]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 621832134-[(Dimethylamino)methyl]-2-nitroanilineHCID 1317369691-(6-Chloropyrimidin-4-yl)-3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methyl-3-((2-(trimethylsilyl)ethoxy)methyl)urea

Product 1

HCID 1317369721-(2,6-Dichloro-3,5-dimethoxy-phenyl)-3-[6-(4-dimethylaminomethyl-2-nitro phenylamino)-pyrimidin-4-yl]-3-methyl-1-(2-trimethylsilanyl-ethoxymethyl)-ureaYield 30%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 1-(6-chloro-pyrimidin-4-yl)-3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-methyl-3-(2-trimethylsilanyl-ethoxymethyl)-urea (procedure L, step b; 260 g, 0.5 mmol) in toluene (5 mL) was added 4-dimethylaminomethyl-2-nitro-phenylamine (100 g, 0.5 mmol), Cs2CO3 (400 g, 1.25 mmol), Pd2(dba)3 (46 g, 0.05 mmol), xantphos (90 g, 0.15 mmol). The solution was stirred at 100° C. overnight. LCMS showed major product peak. The solution was evaporated with silica gel and purified by flash chromatography on silica eluting with EtOAc (w(/0.5% TEA):MeOH (w/0.5% TEA)=10-10:0.5 to afford the desired product (100 mg, yield: 30%). MS (ESI): 680 [M+H]+.

Workup

  1. customThe solution was evaporated with silica gel
  2. custompurified by flash chromatography on silica eluting with EtOAc (w(/0.5% TEA)

Sources & evidence

ORD record
ord-96636bab598d48a1a64d5edaac0f10f2
Source dataset
uspto-grants-2016_09
Patent number
US09434697B2

Reaction notes

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