Triethylamine → tert-Butyl 4-(4-((4-((3-carbamoyl-4-methylphenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate

HRID 1473090Notes

Reaction equation

HRID 1473090 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([CH3:12])=[C:7]([CH:11]=1)[C:8]([NH2:10])=[O:9])#[CH:2].Cl[C:14]1[C:19]([C:20]([F:23])([F:22])[F:21])=[CH:18][N:17]=[C:16]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([N:31]3[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33][CH2:32]3)=[CH:27][CH:26]=2)[N:15]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C>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:8]([C:7]1[CH:11]=[C:3]([C:1]#[C:2][C:18]2[C:19]([C:20]([F:22])([F:21])[F:23])=[CH:14][N:15]=[C:16]([NH:24][C:25]3[CH:26]=[CH:27][C:28]([N:31]4[CH2:32][CH2:33][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:35][CH2:36]4)=[CH:29][CH:30]=3)[N:17]=2)[CH:4]=[CH:5][C:6]=1[CH3:12])(=[O:9])[NH2:10]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 86675713Tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylateHCID 866757225-Ethynyl-2-methylbenzamide

Product 1

HCID 71209810tert-Butyl 4-(4-((4-((3-carbamoyl-4-methylphenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylateYield 69%

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

To a mixture of 5-ethynyl-2-methylbenzamide (I71) (0.041 g, 0.25 mmol), tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate (I3) (0.105 g, 0.230 mmol), PdCl2(PPh3)2 (0.011 g, 0.016 mmol), triphenylphosphine (0.010 g, 0.038 mmol) and copper(I) iodide (0.010 g, 0.53 mmol) in DMF (2 mL) was added triethylamine (0.091 mL, 0.65 mmol). The mixture was then heated under microwave irradiation at 120° C. for 30 minutes. The resulting mixture was concentrated under reduced pressure then purified using silica gel column chromatography (0-100% EtOAc/petroleum benzine 40-60° C.) to give title compound (I72) (0.092 g, 69%); 1H NMR (400 MHz, d5-DMSO) δ 10.24 (s, 1H), 8.75 (s, 1H), 8.31 (s, 1H), 7.90 (s, 1H), 7.58 (m, 4H), 7.39 (m, 1H), 6.96 (d, J=9.0 Hz, 2H), 3.46 (dd, J=6.3, 3.3 Hz, 4H), 3.06 (m, 4H), 2.42 (s, 3H), 1.42 (s, 9H). LCMS Method C: rt 6.22 min; m/z 581.2 [M+H]+.

Workup

  1. concentrationThe resulting mixture was concentrated under reduced pressure
  2. customthen purified
  3. customsilica gel column chromatography (0-100% EtOAc/petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-16f88837600e40fab7e3220d9dd63d8f
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

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