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

HRID 58155Notes

Reaction equation

HRID 58155 reaction equation
[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH2:13])=[C:9]([N+:14]([O-:16])=[O:15])[CH:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Cl[C:18]1[N:23]=[CH:22][N:21]=[C:20]([N:24]([CH3:48])[C:25]([N:27]([C:36]2[C:41]([Cl:42])=[C:40]([O:43][CH3:44])[CH:39]=[C:38]([O:45][CH3:46])[C:37]=2[Cl:47])[CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])=[O:26])[CH:19]=1.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.C([O-])([O-])=O.[Cs+].[Cs+]>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]>[Cl:42][C:41]1[C:40]([O:43][CH3:44])=[CH:39][C:38]([O:45][CH3:46])=[C:37]([Cl:47])[C:36]=1[N:27]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:33])[CH3:34])[C:25]([N:24]([CH3:48])[C:20]1[CH:19]=[C:18]([NH:13][C:10]2[CH:11]=[CH:12][C:7]([N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)=[CH:8][C:9]=2[N+:14]([O-:16])=[O:15])[N:23]=[CH:22][N:21]=1)=[O:26]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 694444684-Morpholin-4-yl-2-nitro-phenylamineHCID 1317369691-(6-Chloropyrimidin-4-yl)-3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methyl-3-((2-(trimethylsilyl)ethoxy)methyl)urea

Product 1

HCID 1317369741-(2,6-Dichloro-3,5-dimethoxy-phenyl)-3-methyl-3-[6-(4-morpholin-4-yl-2-nitro-phenylamino)-pyrimidin-4-yl]-1-(2-trimethylsilanyl-ethoxymethyl)-ureaYield 51.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A degassed mixture of 4-morpholin-4-yl-2-nitro-phenylamine (290 g, 1.3 mmol), 1-(6-chloro-pyrimidin-4-yl)-3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-methyl-3-(2-trimethylsilanyl-ethoxymethyl)-urea (Procedure 2E, step b; 624 g, 1.2 mmol), Pd2(dba)3 (110 g, 0.12 mmol), Xantphos (139 g, 0.24 mmol) and Cs2CO3 (782 g, 2.4 mmol) in toluene (15 mL) was heated at 100° C. for 2.5 hours. The reaction was concentrated, and the residue was purified by chromatography flash on silica to obtain the title compound (440 mg, yield: 49%) as a red solid. MS (ESI): 708 [M+H]+.

Workup

  1. concentrationThe reaction was concentrated
  2. customthe residue was purified by chromatography flash on silica

Sources & evidence

ORD record
ord-9bded0b0410a41edb9f58a3b06868704
Source dataset
uspto-grants-2016_09
Patent number
US09434697B2

Reaction notes

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