Triethylamine → HCID 86712658, compound

HRID 1778999Notes

Reaction equation

HRID 1778999 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:38]=[CH:37][C:36]([CH: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)=[C:35]([CH3:52])[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.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>[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:29])([F:30])[F:31])=[CH:22][N:23]=[C:24]([NH:32][C:33]2[CH:38]=[CH:37][C:36]([CH:39]3[CH2:40][CH2:41][N:42]([C:45]([O:47][C:48]([CH3:50])([CH3:49])[CH3:51])=[O:46])[CH2:43][CH2:44]3)=[C:35]([CH3:52])[CH:34]=2)[N:25]=1

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 45789861Methyl 2-(2-ethynylphenyl)acetateHCID 86712657HCID 86712657, compound

Product 1

HCID 86712658HCID 86712658, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A solution of methyl 2-(2-ethynylphenyl)acetate (K1) (0.103 g, 0.589 mmol) in DMF (1.5 mL) and Et3N (0.273 mL, 1.96 mmol) were added to a suspension of tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)-2-methylphenyl)piperidine-1-carboxylate (A40) (0.231 g, 0.491 mmol), PdCl2(PPh3)2 (0.052 g, 0.074 mmol), CuI (0.014 g, 0.074 mmol) and PPh3 (0.013 g, 0.049 mmol) in DMF (2 mL). The resulting mixture was heated under microwave irradiation at 120° C. for 15 minutes, then diluted with EtOAc and passed through a plug of Celite, washing with EtOAc (60 mL). The filtrate was washed with water (50 mL) and the aqueous layer was extracted with EtOAc (2×50 mL). The combined organics were washed with water (50 mL), brine (50 mL) and dried (Na2SO4). The volatiles were removed in vacuo and the residue was purified by silica gel column chromatography (Biotage Isolera, 25 g SiO2 cartridge, 0-40% EtOAc in petroleum benzine 40-60° C.) to give the title compound A41 as a yellow oil (0.248 g, 83%); 1H NMR (400 MHz, CDCl3) δ 8.62 (s, 1H), 7.68 (dd, J=7.6, 0.9 Hz, 1H), 7.47 (d, J=7.2 Hz, 1H), 7.45-7.40 (m, 1H), 7.39-7.29 (m, 4H), 7.18 (d, J=8.4 Hz, 1H), 4.38-4.21 (m, 2H), 3.96 (s, 2H), 3.70 (s, 3H), 2.92-2.71 (m, 3H), 2.38 (s, 3H), 1.75 (d, J=12.7 Hz, 2H), 1.69-1.54 (m, peak obscured), 1.49 (s, 9H). LCMS-A: rt 6.992 min; m/z 609.1 [M+H]+.

Workup

  1. washwashing with EtOAc (60 mL)
  2. washThe filtrate was washed with water (50 mL)
  3. extractionthe aqueous layer was extracted with EtOAc (2×50 mL)
  4. washThe combined organics were washed with water (50 mL), brine (50 mL)
  5. dry with materialdried (Na2SO4)
  6. customThe volatiles were removed in vacuo
  7. customthe residue was purified by silica gel column chromatography (Biotage Isolera, 25 g SiO2 cartridge, 0-40% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-599bfc808d384153ae3ff73f66d0f3d6
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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