Triethylamine → HCID 86712647, compound

HRID 1778981Notes

Reaction equation

HRID 1778981 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]([O:12][CH3:13])=[O:11])#[CH:2].CCN(CC)CC.Cl[C:22]1[C:27]([C:28]([F:31])([F:30])[F:29])=[CH:26][N:25]=[C:24]([NH:32][C:33]2[CH:53]=[CH:52][C:36]([C:37]([N:39]3[CH2:44][CH2:43][N:42]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:41][CH2:40]3)=[O:38])=[CH:35][CH:34]=2)[N:23]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>CN(C=O)C.CCOC(C)=O.[Cu]I>[CH3:13][O:12][C:10](=[O:11])[CH2:9][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[C:1]#[C:2][C:26]1[C:27]([C:28]([F:30])([F:29])[F:31])=[CH:22][N:23]=[C:24]([NH:32][C:33]2[CH:34]=[CH:35][C:36]([C:37]([N:39]3[CH2:40][CH2:41][N:42]([C:45]([O:47][C:48]([CH3:49])([CH3:50])[CH3:51])=[O:46])[CH2:43][CH2:44]3)=[O:38])=[CH:52][CH:53]=2)[N:25]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 45789861Methyl 2-(2-ethynylphenyl)acetateHCID 86712646tert-Butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzoyl)piperazine-1-carboxylate

Product 1

HCID 86712647HCID 86712647, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A solution of methyl 2-(2-ethynylphenyl)acetate (K1) (0.129 g, 0.741 mmol) in DMF (3 mL) and Et3N (344 μL, 2.47 mmol) was added to a mixture of tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzoyl)piperazine-1-carboxylate (A22) (0.300 g, 0.617 mmol), PdCl2 (PPh3)2 (0.065 g, 0.093 mmol), CuI (0.018 g, 0.093 mmol) and PPh3 (0.016 g, 0.062 mmol) in DMF (3 mL). The resulting mixture was heated under microwave irradiation at 120° C. for 15 minutes, diluted with EtOAc and passed through a plug of Celite, washing with EtOAc (60 mL). The filtrates were combined and the volatiles were removed in vacuo to give a residue that was purified by silica gel column chromatography (Biotage Isolera, 25 g SiO2 cartridge, 0-80% EtOAc in petroleum benzine 40-60° C.) to give the title compound A23 as a yellow oil (0.337 g, 88%); 1H NMR (400 MHz, CDCl3) δ 8.67 (s, 1H), 7.73 (d, J=8.6 Hz, 2H), 7.68 (dd, J=7.7, 1.0 Hz, 1H), 7.61 (s, 1H), 7.48-7.41 (m, 3H), 7.40-7.31 (m, 2H), 3.96 (s, 2H), 3.71 (s, 3H), 3.67-3.37 (m, 8H), 1.47 (s, 9H). LCMS-A: rt 6.393 min; m/z 624.1 [M+H]+.

Workup

  1. washwashing with EtOAc (60 mL)
  2. customthe volatiles were removed in vacuo
  3. customto give a residue that
  4. customwas purified by silica gel column chromatography (Biotage Isolera, 25 g SiO2 cartridge, 0-80% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-f525999ec18b466eaaace98db669a59d
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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