Tetrafluoroborate → HCID 86712712, compound

HRID 1779070Notes

Reaction equation

HRID 1779070 reaction equation
Cl[C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([CH:19]3[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]3)=[CH:15][CH:14]=2)[N:3]=1.F[B-](F)(F)F.[C:37]([C:39]1[CH:44]=[CH:43][C:42]([C:45]([F:48])([F:47])[F:46])=[CH:41][C:40]=1[CH2:49][C:50]([O:52][CH3:53])=[O:51])#[CH:38]>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>[CH3:53][O:52][C:50](=[O:51])[CH2:49][C:40]1[CH:41]=[C:42]([C:45]([F:47])([F:46])[F:48])[CH:43]=[CH:44][C:39]=1[C:37]#[C:38][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([CH:19]3[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]3)=[CH:15][CH:14]=2)[N:3]=1

Participants

6

Reactant 3

HCID 26255TetrafluoroborateHCID 86675716Tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylateHCID 86712711HCID 86712711, compound

Product 1

HCID 86712712HCID 86712712, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalyst

Conditions

Temperature
120 °C

Procedure

A suspension of tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (K5) (0.300 g, 0.656 mmol), PdCl2(PPh3)2 (0.046 g, 0.066 mmol), t-Bu3PH.BF4 (0.019 g, 0.066 mmol), CuI (0.013 g, 0.022 mmol) and methyl 2-(2-ethynyl-5-(trifluoromethyl)phenyl)acetate (A105) (0.191 g, 0.657 mmol) in dry degassed DMF (4 mL) and Et3N (4 mL) was heated at 120° C. for 20 minutes under nitrogen. The volatiles were evaporated under reduced pressure and the residue adsorbed onto silica gel then purified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-50% EtOAc in petroleum benzine 40-60° C.) to give the title compound A106 as a yellow solid (0.196 g, 45%); 1H NMR (400 MHz, CDCl3) δ 8.64 (s, 1H), 7.75 (d, J=8.0 Hz, 1H), 7.62 (s, 1H), 7.60-7.53 (m, 4H), 7.21 (d, J=8.5 Hz, 2H), 4.25 (s, 2H), 3.99 (s, 2H), 3.72 (s, 3H), 2.80 (t, J=11.9 Hz, 2H), 2.64 (m, 1H), 1.82 (d, J=12.8 Hz, 2H), 1.68-1.53 (m, 2H), 1.49 (s, 9H). LCMS-A: rt 7.109 min; m/z 663.3 [M+H]+.

Workup

  1. customdegassed DMF (4 mL) and Et3N (4 mL)
  2. customThe volatiles were evaporated under reduced pressure
  3. customthen purified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-50% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-f9da32bfe61b4974a590384f87d99df3
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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