Tert-butyl 1-(4-(4-chloro-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)ethylcarbamate → tert-Butyl 1-(4-(4-((2-(1-carbamoylcyclopropyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)ethylcarbamate

HRID 592492Notes

Reaction equation

HRID 592492 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1([C:12]([NH2:14])=[O:13])[CH2:11][CH2:10]1)#[CH:2].Cl[C:16]1[C:21]([C:22]([F:25])([F:24])[F:23])=[CH:20][N:19]=[C:18]([NH:26][C:27]2[CH:32]=[CH:31][C:30]([CH:33]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH3:34])=[CH:29][CH:28]=2)[N:17]=1>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[C:12]([C:9]1([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[C:1]#[C:2][C:20]2[C:21]([C:22]([F:23])([F:25])[F:24])=[CH:16][N:17]=[C:18]([NH:26][C:27]3[CH:28]=[CH:29][C:30]([CH:33]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH3:34])=[CH:31][CH:32]=3)[N:19]=2)[CH2:11][CH2:10]1)(=[O:13])[NH2:14]

Participants

6

Reactant 2

HCID 76611269Tert-butyl 1-(4-(4-chloro-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)ethylcarbamateHCID 867122761-(2-Ethynylphenyl)cyclopropanecarboxamide

Product 1

HCID 86712349tert-Butyl 1-(4-(4-((2-(1-carbamoylcyclopropyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)ethylcarbamate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 1-(2-ethynylphenyl)cyclopropanecarboxamide K6 (0.15 g, 0.81 mmol) in DMF (3 mL) was added to a reaction vessel containing tert-butyl 1-(4-(4-chloro-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)ethylcarbamate A80 (0.34 g, 0.81 mmol), PdCl2(PPh3)2 (0.028 g, 0.040 mmol) tri-tert-butylphosphonium tetrafluoroborate (0.023 g, 0.081 mmol) and copper(I)iodide (0.015 g, 0.081 mmol). The mixture was bubbled with nitrogen for 10 minutes before Et3N (1.5 mL) was added. The mixture was heated at 120° C. under microwave irradiation for 15 minutes. The volatiles were removed in vacuo and the residue was purified by silica gel column chromatography (Combiflash Rf, 0-100% EtOAc in cyclohexane) to give the title compound A81 as a yellow oil (0.26 g, 56%). LCMS-C: rt 5.80 min; m/z 566 [M+H]+.

Workup

  1. customThe mixture was bubbled with nitrogen for 10 minutes before Et3N (1.5 mL)
  2. additionwas added
  3. customThe volatiles were removed in vacuo
  4. customthe residue was purified by silica gel column chromatography (Combiflash Rf, 0-100% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-d3b06a80062949b694185bfa34075072
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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