Tetrafluoroborate → tert-Butyl 4-(5-((4-((2-(1-amino-1-oxopropan-2-yl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate

HRID 592475Notes

Reaction equation

HRID 592475 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:14]=[CH:15][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)=[N:17][CH:18]=2)[N:3]=1.[C:32]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[CH:40]([CH3:44])[C:41]([NH2:43])=[O:42])#[CH:33].F[B-](F)(F)F.CCN(C(C)C)C(C)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.O1CCOCC1>[NH2:43][C:41](=[O:42])[CH:40]([C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=1[C:32]#[C:33][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:14]=[CH:15][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)=[N:17][CH:18]=2)[N:3]=1)[CH3:44]

Participants

8

Reactant 4

HCID 26255TetrafluoroborateHCID 81531DiisopropylethylamineHCID 86712273tert-Butyl 4-(5-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylateHCID 867122792-(2-Ethynylphenyl)propanamide

Product 1

HCID 86712342tert-Butyl 4-(5-((4-((2-(1-amino-1-oxopropan-2-yl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of tert-butyl 4-(5-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate A70 (0.397 g, 0.867 mmol), 2-(2-ethynylphenyl)propanamide K7 (0.195 g, 1.13 mmol), CuI (0.011 g, 0.057 mmol), PdCl2(PPh3)2 (0.039 g, 0.056 mmol) and t-Bu3PH.BF4 (0.017 g, 0.058 mmol) under a nitrogen atmosphere was added dioxane (12 mL) and DIPEA (0.60 mL, 3.4 mmol). The mixture was stirred at room temperature for 96 hours before being concentrated under reduced pressure and purifying by silica gel column chromatography (Biotage Isolera, SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C. and 0-20% MeOH in EtOAc) to give the title compound A71 (0.139 g, 27%). LCMS-D: rt 3.626 min; m/z 595.3 [M+H]+.

Workup

  1. concentrationbefore being concentrated under reduced pressure
  2. custompurifying by silica gel column chromatography (Biotage Isolera, SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C. and 0-20% MeOH in EtOAc)

Sources & evidence

ORD record
ord-1e414403de6f4007bfa8bbdd27123de5
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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