Triethylamine → HCID 86712693, compound

HRID 1779050Notes

Reaction equation

HRID 1779050 reaction equation
[C:1]([C:3]1[CH:8]=[C:7]([CH3:9])[CH:6]=[CH:5][C:4]=1[CH2:10][C:11]([O:13][CH3:14])=[O:12])#[CH:2].CCN(CC)CC.Cl[C:23]1[C:28]([C:29]([F:32])([F:31])[F:30])=[CH:27][N:26]=[C:25]([NH:33][C:34]2[CH:39]=[CH:38][C:37]([CH:40]3[CH2:45][CH2:44][N:43]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:42][CH2:41]3)=[CH:36][CH:35]=2)[N:24]=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>[CH3:14][O:13][C:11](=[O:12])[CH2:10][C:4]1[CH:5]=[CH:6][C:7]([CH3:9])=[CH:8][C:3]=1[C:1]#[C:2][C:27]1[C:28]([C:29]([F:30])([F:31])[F:32])=[CH:23][N:24]=[C:25]([NH:33][C:34]2[CH:39]=[CH:38][C:37]([CH:40]3[CH2:41][CH2:42][N:43]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:44][CH2:45]3)=[CH:36][CH:35]=2)[N:26]=1

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 86675716Tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylateHCID 86712694HCID 86712694, compound

Product 1

HCID 86712693HCID 86712693, 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-ethynyl-4-methylphenyl)acetate (A86) (0.196 g, 71% pure) in DMF (3 mL) and Et3N (0.309 mL, 2.22 mmol) was added to a mixture of tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (K5) (0.371 g, 0.812 mmol), PdCl2(PPh3)2 (0.078 g, 0.11 mmol), CuI (0.021 g, 0.11 mmol) and PPh3 (0.019 g, 0.074 mmol) in DMF (3 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 (50 mL). The filtrate was concentrated in vacuo and the residue purified by silica gel column chromatography (Biotage Isolera, 40 g cartridge, 0-35% EtOAc in petroleum benzine 40-60° C.) to give the title compound A87 as a yellow oil (133 mg, 30%); 1H NMR (400 MHz, CDCl3) δ 8.61 (s, 1H), 7.74 (s, 1H), 7.56 (d, J=8.4 Hz, 2H), 7.44 (s, 1H), 7.24-7.16 (m, 4H), 4.43-4.14 (m, 2H), 3.90 (s, 2H), 3.69 (s, 3H), 2.80 (t, J=11.7 Hz, 2H), 2.63 (tt, J=12.0, 3.3 Hz, 1H), 2.34 (s, 3H), 1.81 (d, J=12.7 Hz, 2H), 1.69-1.54 (m, 2H), 1.49 (s, 9H). LCMS-A: rt 7.057 min; m/z 609.3 [M+H]+.

Workup

  1. washwashing with EtOAc (50 mL)
  2. concentrationThe filtrate was concentrated in vacuo
  3. customthe residue purified by silica gel column chromatography (Biotage Isolera, 40 g cartridge, 0-35% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-1e80a9a8def74691b8d51b5ef635047a
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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