Cesium carbonate → tert-Butyl (1-(4-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-methylpyrimidin-2-yl)amino)phenyl)ethyl)carbamate

HRID 592443Notes

Reaction equation

HRID 592443 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2([C:19]([NH2:21])=[O:20])[CH2:18][CH2:17]2)[C:5]([CH3:22])=[CH:4][N:3]=1.[NH2:23][C:24]1[CH:29]=[CH:28][C:27]([CH:30]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])[CH3:31])=[CH:26][CH:25]=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+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:19]([C:16]1([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH2:9][CH2:8][C:6]2[C:5]([CH3:22])=[CH:4][N:3]=[C:2]([NH:23][C:24]3[CH:29]=[CH:28][C:27]([CH:30]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])[CH3:31])=[CH:26][CH:25]=3)[N:7]=2)[CH2:18][CH2:17]1)(=[O:20])[NH2:21]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 22569414tert-butyl N-[1-(4-aminophenyl)ethyl]carbamateHCID 867123151-(2-(2-(2-Chloro-5-methylpyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

Product 1

HCID 86712321tert-Butyl (1-(4-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-methylpyrimidin-2-yl)amino)phenyl)ethyl)carbamate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 1-(2-(2-(2-chloro-5-methylpyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide A40 (0.300 g, 0.950 mmol), tert-butyl (1-(4-aminophenyl)ethyl)carbamate (0.449 g, 1.90 mmol), Pd(OAc)2 (0.004 g, 0.019 mmol), xantphos (0.022 g, 0.038 mmol) and Cs2CO3 (0.929 g, 2.85 mmol) in dioxane (15 mL) was bubbled with N2 for 10 minutes and then stirred in the microwave at 120° C. for 20 minutes. The volatiles were removed in vacuo and the residue was adsorbed onto SiO2 and purified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) to give the title compound A47 as a white solid (0.110 g, 22%). LCMS-D: rt 3.52 min; m/z 516 [M+H]+.

Workup

  1. customwas bubbled with N2 for 10 minutes
  2. customThe volatiles were removed in vacuo
  3. custompurified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-d0ecce1bba7c4638b6eb068e812d15fb
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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