Dimethylformamide → HCID 86712674, compound

HRID 1779023Notes

Reaction equation

HRID 1779023 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]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:42]=[CH:41][C:40]=1[CH2:49][C:50]([O:52][CH3:53])=[O:51])#[CH:38].CN(C=O)C>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.CCN(CC)CC>[CH3:53][O:52][C:50](=[O:51])[CH2:49][C:40]1[CH:41]=[CH:42][C:43]([C:45]([F:47])([F:46])[F:48])=[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

8

Reactant 4

HCID 6228DimethylformamideHCID 26255TetrafluoroborateHCID 86675716Tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylateHCID 86712673HCID 86712673, compound

Product 1

HCID 86712674HCID 86712674, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
120 °C

Procedure

A stirred suspension of tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (K5) (0.200 g, 0.438 mmol), PdCl2(PPh3)2 (0.031 g, 0.044 mmol), t-Bu3PH.BF4 (0.013 mg, 0.044 mmol), CuI (0.008 g, 0.044 mmol) and methyl 2-(2-ethynyl-4-(trifluoromethyl)phenyl)acetate (A59) (0.212 g, 0.875 mmol) in anhydrous, degassed DMF (6 mL) and Et3N (6 mL) was heated at 120° C. for 20 minutes under nitrogen. The volatiles were evaporated under reduced pressure then the residue adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) to give the title compound A60 as a brown solid (0.176 g, 61%); 1H NMR (400 MHz, CDCl3) δ 8.64 (s, 1H), 7.93 (d, J=0.8 Hz, 1H), 7.67 (dd, J=8.2, 1.3 Hz, 1H), 7.56 (d, J=8.5 Hz, 2H), 7.51-7.49 (m, 2H), 7.23 (d, J=8.5 Hz, 2H), 4.36-4.18 (m, 2H), 4.01 (s, 2H), 3.72 (s, 3H), 2.91-2.74 (m, 2H), 2.72-2.58 (m, 1H), 1.83 (d, J=12.6 Hz, 2H), 1.64-1.56 (m, 2H), 1.50 (s, 9H). LCMS-A: rt 7.227 min; m/z 661 [M−H]−.

Workup

  1. customThe volatiles were evaporated under reduced pressure
  2. custompurified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-887d20b218664e26ba6a8ddc5014b849
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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