Tetrafluoroborate → HCID 86712701, compound

HRID 1779057Notes

Reaction equation

HRID 1779057 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([C:9]([F:12])([F:11])[F:10])[C:4]=1[CH2:13][C:14]([O:16][CH3:17])=[O:15])#[CH:2].Cl[C:19]1[C:24]([C:25]([F:28])([F:27])[F:26])=[CH:23][N:22]=[C:21]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([CH:36]3[CH2:41][CH2:40][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38][CH2:37]3)=[CH:32][CH:31]=2)[N:20]=1.F[B-](F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.[Cu]I.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>[CH3:17][O:16][C:14](=[O:15])[CH2:13][C:4]1[C:5]([C:9]([F:11])([F:10])[F:12])=[CH:6][CH:7]=[CH:8][C:3]=1[C:1]#[C:2][C:23]1[C:24]([C:25]([F:26])([F:27])[F:28])=[CH:19][N:20]=[C:21]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([CH:36]3[CH2:37][CH2:38][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:40][CH2:41]3)=[CH:32][CH:31]=2)[N:22]=1

Participants

8

Reactant 4

HCID 26255TetrafluoroborateHCID 81531DiisopropylethylamineHCID 86675716Tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylateHCID 86712700HCID 86712700, compound

Product 1

HCID 86712701HCID 86712701, compound

Reagents, catalysts & solvents 3

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

Conditions

Temperature
110 °C

Procedure

A mixture of methyl 2-(2-ethynyl-6-(trifluoromethyl)phenyl)acetate (A93) (0.113 g, 0.468 mmol), tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (K5) (0.222 g, 0.487 mmol), copper(I) iodide (0.005 g, 0.03 mmol), PdCl2(PPh3)2 (0.021 g, 0.030 mmol) and t-Bu3PH.BF4 (0.011 g, 0.038 mmol) in DMF (2.0 mL) was degassed with nitrogen for several minutes before the addition of DIPEA (2.0 mL, 12 mmol) then further degassed with nitrogen for several minutes. The resulting mixture was heated under microwave irradiation 110° C. for 20 minutes and then a further 30 minutes. The volatiles were evaporated under reduced pressure and the residue purified using silica gel column chromatography (Biotage Isolera, SiO2 cartridge, 0-30% EtOAc in petroleum benzine 40-60° C.) to give the title compound A94 (0.127 g, 41%); 1H NMR (400 MHz, CDCl3) δ 8.63 (s, 1H), 7.88 (d, J=7.3 Hz, 1H), 7.76 (d, J=7.7 Hz, 1H), 7.55 (d, J=8.5 Hz, 2H), 7.47 (t, J=7.7 Hz, 1H), 7.41 (s, 1H), 7.22 (d, J=8.5 Hz, 2H), 4.25 (m, 2H), 4.17 (s, 2H), 3.69 (s, 3H), 2.81 (t, J=12.5 Hz, 2H), 2.65 (m, 1H), 1.83 (d, J=12.6 Hz, 2H), 1.63 (m, 2H), 1.49 (s, 9H). LCMS-A: rt 7.12 min; m/z 661.1 [M−H]+.

Workup

  1. customthen further degassed with nitrogen for several minutes
  2. customa further 30 minutes
  3. customThe volatiles were evaporated under reduced pressure
  4. customthe residue purified
  5. customsilica gel column chromatography (Biotage Isolera, SiO2 cartridge, 0-30% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-f386301ebc77485395cf7a38560a5ffb
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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