Triethylamine → tert-Butyl 4-(4-((4-((2-(1-amino-1-oxopropan-2-yl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)piperidine-1-carboxylate

HRID 592464Notes

Reaction equation

HRID 592464 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]=[N:15][N:16]([CH:18]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]3)[CH:17]=2)[N:3]=1.[C:31]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[CH:39]([CH3:43])[C:40]([NH2:42])=[O:41])#[CH:32].F[B-](F)(F)F.CCN(CC)CC>O1CCOCC1.[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>[NH2:42][C:40](=[O:41])[CH:39]([C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=1[C:31]#[C:32][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]=[N:15][N:16]([CH:18]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]3)[CH:17]=2)[N:3]=1)[CH3:43]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 26255TetrafluoroborateHCID 867122792-(2-Ethynylphenyl)propanamideHCID 86712281tert-Butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Product 1

HCID 86712338tert-Butyl 4-(4-((4-((2-(1-amino-1-oxopropan-2-yl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-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

A mixture of tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)piperidine-1-carboxylate K8 (2.054 g, 4.597 mmol), 2-(2-ethynylphenyl)propanamide K7 (1.027 g, 5.929 mmol), CuI (0.017 g, 0.089 mmol), PdCl2(PPh3)2 (0.062 g, 0.088 mmol) and t-Bu3PH.BF4 (0.025 g, 0.087 mmol) in dioxane (20 mL) and Et3N (2.5 mL, 18 mmol) under a nitrogen atmosphere was heated in the microwave at 110° C. for 40 minutes. The mixture was concentrated under reduced pressure and purified using silica gel column chromatography (50-100% EtOAc in petroleum benzine 40-60° C.) to give the title compound A65 (2.121 g, 79%). 1H NMR (400 MHz, d6-DMSO) δ 10.48-10.33 (m, 1H), 8.82-8.73 (m, 1H), 8.09-7.97 (m, 1H), 7.64-7.55 (m, 2H), 7.56-7.44 (m, 2H), 7.41-7.34 (m, 1H), 7.29-7.22 (m, 1H), 7.01 (s, 1H), 4.39-4.29 (m, 1H), 4.18-3.99 (m, 3H), 2.99-2.80 (m, 2H), 2.02-1.94 (m, 2H), 1.83-1.70 (m, 2H), 1.41 (s, 9H), 1.39-1.31 (m, 3H).

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. custompurified
  3. customsilica gel column chromatography (50-100% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-6407425aaeb5466981cc8b7ec704e184
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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